New experimental method to study acid/base transporters and their regulation in lacrimal gland ductal epithelia.

PubMed

Tóth-Molnár, Edit; Venglovecz, Viktória; Ozsvári, Béla; Rakonczay, Zoltán; Varró, András; Papp, Julius G; Tóth, András; Lonovics, János; Takács, Tamás; Ignáth, Imre; Iványi, Béla; Hegyi, Péter

2007-08-01

The main function of the lacrimal gland is to produce the most aqueous component of the tear film covering the surfaces of the cornea and the conjunctiva. Studies have been conducted that characterize the mixed fluid and protein secretion of isolated acini, but no methods have been developed to characterize lacrimal gland ductal cell (LGDC) secretion. Secretory mechanisms of ductal epithelia may play physiological roles in the maintenance of the standard environments for the cornea and the conjunctiva. In this study, the authors developed a rapid method to isolate large quantities of intact lacrimal ducts. The preparation of isolated intact lacrimal gland ducts for the first time enabled the performance of real-time functional experiments on cleaned ducts. Electron microscopy and fluorescence measurements were used to evaluate the viability of lacrimal ducts. Fluorescence measurements showed that LGDCs express functionally active Na(+)/H(+) exchanger (NHE) and Cl(-)/HCO(3)(-) exchanger (AE). Parasympathomimetic stimulation by carbachol stimulated NHE and AE through the elevation of intracellular calcium concentration. This mechanism can play a role in the regulation of ion and water secretion by LGDCs. The authors have described a lacrimal gland duct isolation technique in which the intact ducts remain viable and the role of duct cells in tear film secretion can be characterized. These data combined with the novel isolation facilitated understanding of the regulation mechanisms of ductal cell secretion at cellular and molecular levels under normal and pathologic conditions.

A review on use of botulinum toxin for intractable lacrimal drainage disorders.

PubMed

Singh, Swati; Ali, Mohammad Javed; Paulsen, Friedrich

2017-08-01

To review the published literature on botulinum toxin (BTX) for epiphora secondary to refractory lacrimal drainage disorders. The authors performed a Pub Med search of all articles published in English on BTX injection into lacrimal gland for epiphora secondary to lacrimal drainage disorders. Relevant cross-references were obtained from the resultant studies. Data reviewed included demographics, indications, dose of BTX, number of injections, transconjunctival or transcutaneous route, outcomes and complications. Animal experiments of BTX into lacrimal gland were included and analyzed separately. Botulinum toxin injection into lacrimal gland, in animal studies, has shown to reduce the tear volume significantly lasting for approximately a month without any histological changes. The major indications have been refractory canalicular obstructions and functional epiphora. The commonly used dose was 2.5 U. Outcomes in the few studies published are encouraging with transient ptosis being the most common complication. Botulinum toxin into the lacrimal gland is a minimally invasive alternative in cases of refractory epiphora secondary to lacrimal drainage disorders. In these subsets of patients, the reported concentrations, dosage and outcome measures are variable and need larger studies for standardization.

Development of Causative Treatment Strategies for Lacrimal Gland Insufficiency by Tissue Engineering and Cell Therapy. Part 2: Reconstruction of Lacrimal Gland Tissue: What Has Been Achieved So Far and What Are the Remaining Challenges?

PubMed

Massie, Isobel; Dietrich, Jana; Roth, Mathias; Geerling, Gerd; Mertsch, Sonja; Schrader, Stefan

2016-10-01

The lacrimal gland is located in the upper temporal compartment of the orbita, and along with the ocular surface, eye lids, and sensory and motor nerves forms the lacrimal functional unit (LFU). The LFU is responsible for producing, distributing, and maintaining the tear film in order to maintain a smooth, moist, and regular ocular surface epithelium such that appropriate refractive properties are achieved and the eyeball is protected against dust, debris, and pathogens. If the main lacrimal gland is impaired (due to either disease or injury), this balance is disrupted, and severe quantitative dry eye syndrome (DES) can develop. DES treatments remain palliative, with the most commonly used therapies being based on tear substitution, tear retention, and control of inflammation on the ocular surface. Causative treatments such as salivary gland transplantation have shown to reduce symptoms in very severe cases, however can cause problems on the ocular surface due to different properties of saliva and tears. Therefore, causative approaches for treating DES by regeneration or reconstruction of lacrimal gland tissue depending on disease severity seem highly appealing. This article reviews current approaches for in vitro reconstruction of lacrimal gland tissue. Finally, the limitations that must be overcome before a new, tissue-engineered therapy may be delivered to clinic will be discussed.

Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development

PubMed Central

Qu, Xiuxia; Pan, Yi; Carbe, Christian; Powers, Andrea; Grobe, Kay; Zhang, Xin

2012-01-01

Glycosaminoglycans (GAGs) play a central role in embryonic development by regulating the movement and signaling of morphogens. We have previously demonstrated that GAGs are the co-receptors for Fgf10 signaling in the lacrimal gland epithelium, but their function in the Fgf10-producing periocular mesenchyme is still poorly understood. In this study, we have generated a mesenchymal ablation of UDP-glucose dehydrogenase (Ugdh), an essential biosynthetic enzyme for GAGs. Although Fgf10 RNA is expressed normally in the periocular mesenchyme, Ugdh mutation leads to excessive dispersion of Fgf10 protein, which fails to elicit an FGF signaling response or budding morphogenesis in the presumptive lacrimal gland epithelium. This is supported by genetic rescue experiments in which the Ugdh lacrimal gland defect is ameliorated by constitutive Ras activation in the epithelium but not in the mesenchyme. We further show that lacrimal gland development requires the mesenchymal expression of the heparan sulfate N-sulfation genes Ndst1 and Ndst2 but not the 6-O and 2-O-sulfation genes Hs6st1, Hs6st2 and Hs2st. Taken together, these results demonstrate that mesenchymal GAG controls lacrimal gland induction by restricting the diffusion of Fgf10. PMID:22745308

Mitochondria-targeted antioxidant SkQ1 reduces age-related alterations in the ultrastructure of the lacrimal gland

PubMed Central

Bakeeva, Lora E.; Eldarov, Chupalav M.; Vangely, Irina M.; Kolosova, Nataliya G.; Vays, Valeriya B.

2016-01-01

Dry eye syndrome is an eye disorder affecting many people at an old age. Because dry eye syndrome is accelerated by aging, a useful approach to the prevention of this syndrome may be an intervention into the aging process. Previously, we showed that the mitochondria-targeted antioxidant SkQ1 delays manifestations of aging and inhibits the development of age-related diseases including dry eye syndrome. Nevertheless, the link between SkQ1's effects and its suppression of age-related changes in the lacrimal gland remains unclear. Here we demonstrated that dietary supplementation with SkQ1 (250 nmol/[kg body weight] daily) starting at age 1.5 months significantly alleviated the pathological changes in lacrimal glands of Wistar rats by age 24 months. By this age, lacrimal glands underwent dramatic deterioration of the ultrastructure that was indicative of irreversible disturbances in these glands' functioning. In contrast, in SkQ1-treated rats, the ultrastructure of the lacrimal gland was similar to that in much younger rats. Morphometric analysis of electron-microscopic specimens of lacrimal glands revealed the presence of numerous secretory granules in acinar cells and a significant increase in the number of operating intercalary ducts. Our results confirm that dietary supplementation with SkQ1 is a promising approach to healthy ageing and to prevention of aberrations in the lacrimal gland that underlie dry eye syndrome. PMID:27852065

Pleomorphic adenoma of a deep orbital ectopic lacrimal gland.

PubMed

Misra, Somen; Bhandari, Akshay; Misra, Neeta; Gogri, Pratik; Mahajan, Shruti

2016-10-01

Ectopic lacrimal gland, being one of the choristomas, is comprised of lacrimal gland tissue outside the lacrimal gland fossa in the fronto-lateral part of the orbital roof. Ectopic lacrimal gland is a rare condition where the gland may be found in the orbit, eyelids, ocular adnexa or within the globe. Neoplastic transformation of such tissue may occur. A sixty-two-year old male patient presented with right eye proptosis and slight nasal displacement of the globe. Computerized tomography scan revealed a well-defined hypodense lesion of size 19 x 18 x 20 mm supero-lateral to lateral rectus muscle, with mild proptosis and thinning of the right lateral orbital wall. Excisional biopsy was performed through a lateral orbitotomy approach. A well circumscribed globular mass was removed from the right orbit, well behind the fossa for the lacrimal gland in the retrobulbar space. Histopathology was suggestive of pleomorphic adenoma of lacrimal gland. Pleomorphic adenoma is an epithelial tumor of the lacrimal gland which is extremely rare from an ectopic lacrimal gland and only few cases have been reported in literature till date.

Mechanisms Involved in Injury and Repair of the Murine Lacrimal Gland: Role of Programmed Cell Death and Mesenchymal Stem Cells

PubMed Central

Zoukhri, Driss

2011-01-01

The non-keratinized epithelia of the ocular surface are constantly challenged by environmental insults, such as smoke, dust, and airborne pathogens. Tears are the sole physical protective barrier for the ocular surface. Production of tears in inadequate quantity or of inadequate quality results in constant irritation of the ocular surface, leading to dry eye disease, also referred to as keratoconjunctivitis sicca (KCS). Inflammation of the lacrimal gland, such as occurs in Sjögren’s syndrome, sarcoidosis, chronic graft versus-host disease, and other pathological conditions, results in inadequate secretion of the aqueous layer of the tear film, and is a leading cause of dry eye disease. The hallmarks of lacrimal gland inflammation are the presence of immune cell infiltrates, loss of acinar epithelial cells (the secreting cells), and increased production of proinflammatory cytokines. To date, the mechanisms leading to acinar cell loss and the associated decline in lacrimal gland secretion are still poorly understood. It is also not understood why the remaining lacrimal gland cells are unable to proliferate in order to regenerate a functioning lacrimal gland. This article reviews recent advances in exocrine tissue injury and repair, with emphasis on the roles of programmed cell death and stem/progenitor cells. PMID:20427009

Oxidative Stress Induced Inflammation Initiates Functional Decline of Tear Production

PubMed Central

Uchino, Yuichi; Kawakita, Tetsuya; Miyazawa, Masaki; Ishii, Takamasa; Onouchi, Hiromi; Yasuda, Kayo; Ogawa, Yoko; Shimmura, Shigeto; Ishii, Naoaki; Tsubota, Kazuo

2012-01-01

Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1) using a modified tetracycline system (Tet-On/Off system). This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC) in humans). The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease. PMID:23071526

Expression profiles of aquaporins in rat conjunctiva, cornea, lacrimal gland and Meibomian gland.

PubMed

Yu, Dongfang; Thelin, William R; Randell, Scott H; Boucher, Richard C

2012-10-01

The aim of the study was to elucidate aquaporin (AQP) family member mRNA expression and protein expression/localization in the rat lacrimal functional unit. The mRNA expression of all rat AQPs (AQP0-9, 11-12) in palpebral, fornical, and bulbar conjunctiva, cornea, lacrimal gland, and Meibomian gland was measured by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and real time RT-PCR. Antibodies against AQP1, 3, 4, 5, 9, and 11 were used in Western blotting and immunohistochemistry to determine protein expression and distribution. Our study demonstrated characteristic AQP expression profiles in rat ocular tissues. AQP1, 3, 4, 5, 8, 9, 11, and 12 mRNA were detected in conjunctiva. AQP0, 1, 2, 3, 4, 5, 6, 11, and 12 mRNA were expressed in cornea. AQP0, 1, 2, 3, 4, 5, 7, 8, and 11 mRNA were detected in lacrimal gland. AQP1, 3, 4, 5, 7, 8, 9, 11, and 12 mRNA were identified in Meibomian gland. By Western blot, AQP1, 3, 5, and 11 were detected in conjunctiva; AQP1, 3, 5, and 11 were identified in cornea; AQP1, 3, 4, 5, and 11 were detected in lacrimal gland; and AQP1, 3, 4, 5, 9, and 11 were present in Meibomian gland. Immunohistochemistry localized AQPs to distinct sites in the various tissues. This study rigorously analyzed AQPs expression and localization in rat conjunctiva, cornea, lacrimal gland, and Meibomian gland tissues. Our findings provide a comprehensive platform for further investigation into the physiological or pathophysiological relevance of AQPs in ocular surface. Copyright © 2012 Elsevier Ltd. All rights reserved.

Isotretinoin in lacrimal gland fluid and tears.

PubMed

Rismondo, V; Ubels, J L

1987-03-01

Isotretinoin (13-cis-retinoic acid) is used in the treatment of severe cystic acne. Adverse ocular reactions, including blepharoconjunctivitis and dry eye symptoms, are frequent side effects of this drug. Our previous observation that retinol is present in tears and lacrimal gland fluid suggests that isotretinoin may also be secreted by the lacrimal gland. Rabbits were treated with isotretinoin, and lacrimal gland fluid was collected from the cannulated lacrimal gland duct. Tears were collected from patients who were being treated with isotretinoin. Lacrimal gland fluid and tears were analyzed by reverse-phase high-pressure liquid chromatography and a peak eluted from each sample, which was identified as isotretinoin. We conclude that the lacrimal gland is able to secrete isotretinoin in addition to retinol and that, in animals and patients treated systemically with isotretinoin, the ocular surface is exposed to the drug via the tear film.

Characterization of cultivated murine lacrimal gland epithelial cells

PubMed Central

Kobayashi, Shinya; Kawashima, Motoko; Okada, Naoko; Mishima, Kenji; Saito, Ichiro; Ito, Masataka; Shimmura, Shigeto; Tsubota, Kazuo

2012-01-01

Purpose To date, mouse lacrimal gland epithelial cells have been cultured successfully but only in cases involving newborn mouse lacrimal glands. In this work, we attempted to cultivate and characterize adult mouse lacrimal gland epithelial cells. Methods Lacrimal glands were removed from newborn mice (C57B/6) and isolated lacrimal gland epithelial cells were seeded onto tissue culture treated or low adherent culture dishes in Cnt-07 culture medium with or without cholera toxin. Cultivated cells were characterized by immunostaining with pan-cytokeratin, α-smooth muscle actin, and lactoferrin antibodies. Lacrimal gland cells from 7-week-old green fluorescent protein (GFP) and non-GFP (C57B/6) mice were mixed and seeded onto uncoated dishes to assess sphere-forming efficiency. Cells were also seeded onto 3T3 cell feeder layers to assess colony forming efficiency. Results Lacrimal gland epithelial cells were selectively cultured with cholera toxin, and cell type was verified by pan-cytokeratin and α-smooth muscle actin immunostaining. Sphere formation from single cells of adult mice was observed using specific medium and low adherent culture dishes. These cells could also undergo colony formation on 3T3 feeder cells. Conclusions Adult mouse lacrimal gland epithelial cells were successfully cultivated in cholera toxin-containing medium, and were observed to form spheres from single cells. PMID:22665974

The Epidemiological, Clinical, and Histopathological Characteristics of Lacrimal Gland Biopsies in a Tertiary Care Center in Israel.

PubMed

Priel, Ayelet; Vishnevskia-Dai, Vicktoria; Hochma, Liran; Gildener-Leapman, Juliana; Ben Simon, Guy J; Rosner, Mordechai; Antman, Gal; Zloto, Ofira

2018-02-01

The distribution of pathology and clinical characteristics of lacrimal gland diseases are different in different areas of the world. To evaluate the incidence rate, patient characteristics, and indications for surgical intervention of lacrimal gland lesions in a tertiary care center in Israel. All biopsied or surgically removed lacrimal gland lesions at the Goldschleger Eye Institute from 2009 to 2015 were identified. The following data were collected: age, gender, indications for surgical intervention, diagnosis, treatment, and prognosis. We evaluated 28 lacrimal gland biopsies from 26 patients (11 men, 15 women). Mean age at biopsy was 47.5 years old. The most common presenting symptoms were: eyelid swollenness (57.14%), ptosis (32.14%), and proptosis (10.71%). All patients underwent computed tomography and magnetic resonance imaging. In 28 cases, infiltrations of the lacrimal gland were found. In nine cases infiltration of muscles or orbital extension were found. The most common pathologies were non-specified inflammation (44.82%), lymphoma (20.68%), and immunoglobulin G4-related disease (10.34%). The treatment was diverse according to the patient diagnosis. Prognosis of lacrimal gland disease was good; however, in five patients the systemic disease progressed. Lesions of the lacrimal gland comprise a wide variety of pathological findings that require different treatment strategies. Lacrimal gland biopsies enable physicians to precisely recognize the pathology; therefore, it is important to consider this surgical method in any patient with lesions in the lacrimal gland.

Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles.

PubMed

Andreasen, Simon; Tan, Qihua; Agander, Tina Klitmøller; Steiner, Petr; Bjørndal, Kristine; Høgdall, Estrid; Larsen, Stine Rosenkilde; Erentaite, Daiva; Olsen, Caroline Holkmann; Ulhøi, Benedicte Parm; von Holstein, Sarah Linéa; Wessel, Irene; Heegaard, Steffen; Homøe, Preben

2018-02-21

Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.

Lacrimal gland uptake of (67)Ga-gallium citrate correlates with biopsy results in patients with suspected sarcoidosis.

PubMed

Tannen, Bradford L; Kolomeyer, Anton M; Turbin, Roger E; Frohman, Larry; Langer, Paul D; Oh, Cheongeun; Ghesani, Nasrin V; Zuckier, Lionel S; Chu, David S

2014-02-01

To investigate whether lacrimal gland uptake on (67)Ga-gallium citrate scintigraphy correlates with histopathologic evidence of sarcoidosis. A retrospective, pilot study of 31 patients with suspected sarcoidosis who underwent gallium scintigraphy and lacrimal gland biopsy. Lacrimal gland gallium uptake was assessed by subjective visual scoring (SVS) and lacrimal uptake ratio (LUR). Eleven (36%) patients had lacrimal gland biopsies containing noncaseating granulomas. A statistically significant correlation was found between lacrimal gland gallium uptake and biopsy positivity using SVS (p = 0.03) or LUR (p = 0.01). Using SVS, biopsy positivity rate increased from 0 to 50% in patients with mild to intense uptake. Using LUR, biopsy positivity rate increased linearly as the ratio increased from 13% (LUR < 4) to 100% (LUR > 8). Lacrimal biopsy positivity rate significantly correlated with gallium uptake on scintigraphy. Both SVS and LUR methods appear to correlate with histologic results and may potentially aid in patient selection for biopsy.

[Neuronal and hormonal regulatory mechanisms of tears production and secretion].

PubMed

Mrugacz, Małgorzata; Zywalewska, Nella; Bakunowicz-Lazarczyk, Alina

2005-01-01

The ocular surface, tear film, lacrimal glands act as a functional unit to preserve the quality of the refractive surface of the eye, and to resist injury and protect the eye against bodily and environmental conditions. Homeostasis of this functional unit involves neuronal and hormonal regulatory mechanisms. The eye appears to be a target organ for sex hormones particulary the androgen, as they modulate the immune system and trophic functions of the lacrimal and Meibomian glands.

Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation

PubMed Central

Ji, Yong Woo; Mittal, Sharad K.; Hwang, Ho Sik; Chang, Eun-Ju; Lee, Joon H.; Seo, Yuri; Yeo, Areum; Noh, Hyemi; Lee, Hye Sun; Chauhan, Sunil K.; Lee, Hyung Keun

2016-01-01

Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED), and in severe cases can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands, not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knock-out mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of lacrimal gland-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target. PMID:28051088

Sjögren-Like Lacrimal Keratoconjunctivitis in Germ-Free Mice

PubMed Central

Wang, Changjun; Zaheer, Mahira; Bian, Fang; Quach, Darin; Swennes, Alton G.; Britton, Robert A.; Pflugfelder, Stephen C.

2018-01-01

Commensal bacteria play an important role in the formation of the immune system but their role in the maintenance of immune homeostasis at the ocular surface and lacrimal gland remains poorly understood. This study investigated the eye and lacrimal gland phenotype in germ-free and conventional C57BL/6J mice. Our results showed that germ-free mice had significantly greater corneal barrier disruption, greater goblet cell loss, and greater total inflammatory cell and CD4+ T cell infiltration within the lacrimal gland compared to the conventionally housed group. A greater frequency of CD4+IFN-γ+ cells was observed in germ-free lacrimal glands. Females exhibited a more severe phenotype compared to males. Adoptive transfer of CD4+ T cells isolated from female germ-free mice into RAG1KO mice transferred Sjögren-like lacrimal keratoconjunctivitis. Fecal microbiota transplant from conventional mice reverted dry eye phenotype in germ-free mice and decreased CD4+IFN-γ+ cells to levels similar to conventional C57BL/6J mice. These findings indicate that germ-free mice have a spontaneous lacrimal keratoconjunctivitis similar to that observed in Sjögren syndrome patients and demonstrate that commensal bacteria function in maintaining immune homeostasis on the ocular surface. Thus, manipulation of intestinal commensal bacteria has the potential to become a novel therapeutic approach to treat Sjögren Syndrome. PMID:29438346

Breast carcinoma metastasis to the lacrimal gland: Two case reports

PubMed Central

NICKELSEN, MARIE N.; VON HOLSTEIN, SARAH; HANSEN, ALASTAIR B.; PRAUSE, JAN U.; HEEGAARD, STEFFEN

2015-01-01

A 77-year-old female, with proptosis, reduced eye motility and diplopia which had developed over two to three months and a 69-year-old female with proptosis, oedema of the eyelid, reduced motility and ptosis, which had developed over three weeks, are presented in the present study. Computed tomography scans revealed irregular lacrimal gland tumours in the two patients. The two patients had history of breast cancer. The first breast cancer metastasis in the lacrimal gland demonstrated a cribriform growth pattern containing ductal elements. The epithelial tumour cells stained positive for cytokeratin (1–8, 10, 14–16, 18 and 19), oestrogen receptor, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and gross cystic disease fluid protein 15 (GCDFP-15). The second metastatic tumour was positive for EMA and estrogen receptor, but variably positive for CEA and GCDFP-15. The metastasis in the lacrimal gland was a pleomorphic tumour. The tumour cells were positive for EMA and variably positive for oestrogen and CEA. Metastases to the lacrimal gland are extremely rare, and metastases to the lacrimal gland should be considered in the diagnoses of lacrimal gland tumours. The present study aimed to describe two such cases and draw attention to breast carcinomas as a differential diagnosis and the most frequent cause of lacrimal gland metastasis. PMID:26622620

Effects of Aging in Dry Eye

PubMed Central

de Paiva, Cintia S.

2017-01-01

Dry eye affects millions of people worldwide and causes eye well recognized risk factors for dry eye. Anatomical and inflammation-induced age-related changes affect all components of the lacrimal gland functional unit, inclusive of lacrimal gland, conjunctiva, meibomian gland and compromise ocular surface health. There is increased evidence that inflammation plays a role in dry eye. This review will summarize the current knowledge about aging and dry eye, inclusive of lessons learned from animal models and promising therapies. PMID:28282314

An in vitro evaluation of various biomaterials for the development of a tissue-engineered lacrimal gland

NASA Astrophysics Data System (ADS)

Selvam, Shivaram

The most common cause of ocular morbidity in developed countries is dry eye, many cases of which are due to lacrimal insufficiency. It has been established that lacrimal insufficiency results from processes caused by both immune-related and non-immune related events such as Sjogren's syndrome, Stevens-Johnson syndrome, chemical and thermal injuries and ocular cicatricial pemphigoid. Patients with these conditions would benefit from repair of their damaged lacrimal tissue by the creation of a replacement for the lacrimal gland. The new field of tissue engineering built on the interface between principles and methods of the life sciences with those of engineering to develop biocompatible materials has created the possibility for repairing or replacing damaged tissues. This thesis explores the use of tissue engineering principles for the development of a tissue-engineered lacrimal gland. This thesis also contributes to the development of a novel model for addressing lacrimal gland physiology and epithelial fluid transport. The first part of the research work focused on the evaluation of morphological and physiological properties of purified lacrimal gland acinar cells (pLGACs) cultured on various biopolymers: silicone, collagen I, poly-D,L-lactide-co-glycolide (PLGA; 85:15 and 50:50), and poly-L-lactic acid (PLLA) in the presence and absence of an extracellular matrix, MatrigelRTM. Results indicated that PLLA demonstrated the best support expression of acinar cell-like morphology. The second part demonstrated the ex vivo reconstitution of an electrophysiologically functional lacrimal gland tissue on porous polyester membrane scaffolds. Results showed that pLGACs were capable of establishing continuous epithelial monolayers that generate active ionic fluxes consistent with current models for Na +-dependent Cl-- secretion. The third part outlined the fabrication of porous PLLA membranes, the optimal biomaterial for culturing lacrimal epithelial cells. Microporous PLLA-Polyethylene glycol (PEG) blend membranes (mpPLLAbm) with interconnected pores were prepared by the water extraction of PEG from solution cast blend membranes using the solvent-cast/particulate leaching technique. Diffusion experiments on mpPLLAbm (57.1/42.9 wt%) were performed to demonstrate that the membrane was permeable to glucose, L-tryptophan, and dextran.

Influence of ribosomal protein L39-L in the drug resistance mechanisms of lacrimal gland adenoid cystic carcinoma cells.

PubMed

Ye, Qing; Ding, Shao-Feng; Wang, Zhi-An; Feng, Jie; Tan, Wen-Bin

2014-01-01

Cancer constitutes a key pressure on public health regardless of the economy state in different countries. As a kind of highly malignant epithelial tumor, lacrimal gland adenoid cystic carcinoma can occur in any part of the body, such as salivary gland, submandibular gland, trachea, lung, breast, skin and lacrimal gland. Chemotherapy is one of the key treatment techniques, but drug resistance, especially MDR, seriously blunts its effects. As an element of the 60S large ribosomal subunit, the ribosomal protein L39-L gene appears to be documented specifically in the human testis and many human cancer samples of different origins. Total RNA of cultured drug-resistant and susceptible lacrimal gland adenoid cystic carcinoma cells was seperated, and real time quantitative RT-PCR were used to reveal transcription differences between amycin resistant and susceptible strains of lacrimal gland adenoid cystic carcinoma cells. Viability assays were used to present the amycin resistance difference in a RPL39-L transfected lacrimal gland adenoid cystic carcinoma cell line as compared to control vector and null-transfected lacrimal gland adenoid cystic carcinoma cell lines. The ribosomal protein L39-L transcription level was 6.5-fold higher in the drug-resistant human lacrimal gland adenoid cystic carcinoma cell line than in the susceptible cell line by quantitative RT-PCR analysis. The ribosomal protein L39-L transfected cells revealed enhanced drug resistance compared to plasmid vector-transfected or null-transfected cells as determined by methyl tritiated thymidine (3H-TdR) incorporation. The ribosomal protein L39-L gene could possibly have influence on the drug resistance mechanism of lacrimal gland adenoid cystic carcinoma cells.

Production and localization of Muc4/sialomucin complex and its receptor tyrosine kinase ErbB2 in the rat lacrimal gland.

PubMed

Arango, M E; Li, P; Komatsu, M; Montes, C; Carraway, C A; Carraway, K L

2001-11-01

To show the presence and forms of sialomucin complex (rat Muc4) and receptor tyrosine kinase ErbBs in the rat lacrimal gland and analyze for complexes of ErbB2 and its ligand Muc4. Northern blot analyses were used to identify sialomucin complex/Muc4 (SMC/Muc4) mRNA in rat lacrimal gland. Immunoblot analyses were performed to detect SMC/Muc4 and ErbBs. Sequential immunoprecipitation and immunoblot analyses were used to differentiate membrane and soluble forms of the SMC/Muc4 transmembrane subunit ASGP-2. Methacarn-fixed, paraffin-embedded sections of lacrimal glands from female adult rats were immunocytochemically stained using antisera to SMC/Muc4 and ErbBs to determine their relative locations in the gland. Colocalization of SMC/Muc4 and ErbB2 was confirmed by confocal immunofluorescence. Sequential immunoprecipitation and immunoblot were performed to analyze complexes of the SMC/Muc4 and ErbB2 in the lacrimal tissue. Northern blot analyses of rat lacrimal glands, with a probe for SMC/Muc4, demonstrated the presence of a approximately 9-kb transcript, consistent with observations in other tissues. Similarly, immunoblot analyses with antibodies against both the transmembrane (ASGP-2) and mucin (ASGP-1) subunits showed the presence of the two SMC/Muc4 subunits in lysates from rat lacrimal gland. Significantly, two different forms of ASGP-2 were observed, a high-molecular-weight ( approximately 200-kDa) form and the more common 120- to 140-kDa form. Sequential immunoprecipitation and immunoblot analyses to differentiate membrane and soluble forms of SMC/Muc4 indicated that the high-molecular-weight form of ASGP-2 was predominantly associated with membranes, whereas the 120- to 140-kDa form was both membrane-associated and soluble. The lacrimal gland consists of acini connected by intercalated and interlobular ducts. Both acini and some intercalated ducts were stained by anti-ASGP-2 monoclonal antisera. Two patterns of acinar staining were observed: membrane staining at the borders of the epithelial cells and a granular staining within the cells. Staining of ductal surfaces with antibody to the cytoplasmic domain of ASGP-2 suggests that membrane SMC/Muc4 is being produced by the ductal cells and is not simply an adsorbed soluble product from the acinar cells. Immunoblot and immunocytochemical analyses demonstrated the presence of all four ErbBs, with ErbB2 showing the most widespread distribution, similar to that of SMC/Muc4. Immunofluorescence colocalization of membrane SMC/Muc4 and ErbB2 and coimmunoprecipitation of a complex of the two provided evidence of their association in membranes of lacrimal gland acinar cells. SMC/Muc4 is produced by the rat lacrimal gland as both membrane and soluble forms, specifically associated with both acinar and ductal cells. Because sialomucin complex is also present in the ocular tear film, the rat lacrimal gland represents a second source of this mucin for the tear film, in addition to the corneal and conjunctival epithelia. Moreover, the presence of a complex of SMC/Muc4 and the receptor tyrosine kinase ErbB2 in lacrimal tissue suggests that SMC/Muc4 acts as a ligand for the receptor and has functions in the lacrimal gland other than that of a mucin.

Lacrimal Gland Radiosensitivity in Uveal Melanoma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muller, Karin; Nowak, Peter J.C.M.; Naus, Nicole

2009-06-01

Purpose: To find a dose-volume effect for inhomogeneous irradiated lacrimal glands. Methods and Materials: Between 1999 and 2006, 72 patients (42 men and 30 women) were treated with fractionated stereotactic radiotherapy in a prospective, nonrandomized clinical trial (median follow-up, 32 months). A total dose of 50 Gy was given on 5 consecutive days. The mean of all Schirmer test results obtained {>=}6 months after treatment was correlated with the radiation dose delivered to the lacrimal gland. Also, the appearance of dry eye syndrome (DES) was related to the lacrimal gland dose distribution. Results: Of the 72 patients, 17 developed amore » late Schirmer value <10 mm; 9 patients developed DES. A statistically significant relationship was found between the received median dose in the lacrimal gland vs. reduced tear production (p = 0.000) and vs. the appearance of DES (p = 0.003), respectively. A median dose of 7 Gy/fraction to the lacrimal gland caused a 50% risk of low Schirmer results. A median dose of 10 Gy resulted in a 50% probability of DES. Conclusion: We found a clear dose-volume relationship for irradiated lacrimal glands with regard to reduced tear production and the appearance of DES.« less

Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis

PubMed Central

Garg, Ankur; Gotoh, Noriko; Feng, Gen-Sheng; Zhong, Jian; Wang, Fen; Kariminejad, Ariana; Brooks, Steven

2017-01-01

The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development. PMID:29028795

Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis.

PubMed

Garg, Ankur; Bansal, Mukesh; Gotoh, Noriko; Feng, Gen-Sheng; Zhong, Jian; Wang, Fen; Kariminejad, Ariana; Brooks, Steven; Zhang, Xin

2017-10-01

The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development.

Botulinum neurotoxin A injection for the treatment of epiphora with patent lacrymal ducts.

PubMed

Girard, B; Piaton, J-M; Keller, P; Nguyen, T H

2018-04-01

Retrospective longitudinal study to evaluate the efficacy of botulinum neurotoxin A (BoNT/A) therapy for epiphora with patent lacrimal ducts. BoNT/A has been used since 2000 in axillary hyperhidrosis to reduce sweat secretion. Some isolated cases of hyperlacrimation or crocodile tear syndrome have been treated with BoNT/A on this basis. We report our experience in the treatment of tearing despite patent lacrimal ducts by BoNT/A injection into the lacrimal gland. We reviewed qualitative and quantitative criteria to evaluate the degree of improvement of epiphora after BoNT/A injections in the palpebral lobe of the lacrimal gland in patients referred for epiphora despite patent lacrimal ducts between 2009 and 2016. Epiphora was graded using a functional questionnaire, Munk score and Schirmer test performed before and after the injections. Side effects were recorded. Sixty-five palpebral lacrimal glands of forty-two patients with epiphora despite patent lacrimal ducts, of mean age 65 years, sex ratio 0.8, were treated with BoNT/A (IncobotulinumtoxinA, XEOMIN ® , MERZ Pharma France) from April 2009 to April 2016. The etiology of the epiphora was represented by 56 paroxysmal lacrimal hypersecretion, 2 crocodile tear syndrome and 7 facial palsies. No conventional medical or surgical treatment had been effective in these cases. The technique of injection, dilution and dosage of BoNT/A were specific. We re-injected 33/65 cases a second time upon patient request due to recurrence of epiphora, 16/65 cases three times, 8/65 cases four times, 6/65 cases five times and 3/65 six times. The Schirmer's test measured a decrease of lacrimal secretion in 51/65 glands (78%) after the first botulinum neurotoxin injection. Side effects were limited to ptosis in 2 cases (3%) and six patients (9%) with rapidly regressing diplopia. Two patients experienced immediate lacrimal gland hematoma (3%) with no sequelae. The authors describe the injection techniques, the dosage, the volume and concentration of BoNT/A. Patients with intractable epiphora despite patent lacrimal ducts can be effectively treated with BoNT/A (IncobotulinumtoxinA) injection into the palpebral lobe of the lacrimal gland. Most of the patients (80%) were very satisfied with few side effects (hematoma, ptosis or mild diplopia lasting from 3 days to 3 weeks). More studies are needed to delineate which types of epiphora can be treated with BoNT A. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Neural Regulation of Lacrimal Gland Secretory Processes: Relevance in Dry Eye Diseases

PubMed Central

Dartt, Darlene A.

2013-01-01

The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins. The amount and composition of this layer is critical for the health, maintenance, and protection of the cells of the cornea and conjunctiva (the ocular surface). Small changes in the concentration of tear electrolytes have been correlated with dry eye syndrome. While the mechanisms of secretion of water, electrolytes and proteins from the lacrimal gland differ, all three are under tight neural control. This allows for a rapid response to meet the needs of the cells of the ocular surface in response to environmental conditions. The neural response consists of the activation of the afferent sensory nerves in the cornea and conjunctiva to stimulate efferent parasympathetic and sympathetic nerves that innervate the lacrimal gland. Neurotransmitters are released from the stimulated parasympathetic and sympathetic nerves that cause secretion of water, electrolytes, and proteins from the lacrimal gland and onto the ocular surface. This review focuses on the neural regulation of lacrimal gland secretion under normal and dry eye conditions. PMID:19376264

Electronic enhancement of tear secretion

NASA Astrophysics Data System (ADS)

Brinton, Mark; Lim Chung, Jae; Kossler, Andrea; Kook, Koung Hoon; Loudin, Jim; Franke, Manfred; Palanker, Daniel

2016-02-01

Objective. To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion. Approach. We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz). Main results. Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm-2 with 170-680 μs pulses) than the damage threshold (3.5 μC mm-2 with 1 ms pulses). Significance. Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and further optimize electrical parameters for maximum clinical efficacy.

Dynamic Ocular Surface and Lacrimal Gland Changes Induced in Experimental Murine Dry Eye

PubMed Central

Xiao, Bing; Wang, Yu; Reinach, Peter S.; Ren, Yueping; Li, Jinyang; Hua, Shanshan; Lu, Huihui; Chen, Wei

2015-01-01

Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjögren’s Syndrome or increased tear film evaporation despite normal lacrimal gland function. To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period. Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an Intelligently Controlled Environmental System (ICES). Sixty mice were housed in ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal environment and received subcutaneous injections of scopolamine hydrobromide (SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal environment and received no treatment. Corneal fluorescein staining along with corneal MMP-9 and caspase-3 level measurements were performed in parallel with the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-β2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light and transmission electron microscopy studies evaluated LGs cytoarchitectural changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2 weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland proinflammatory cytokine level increases were much lower than those in the SCOP group. In accord with the lower proinflammatory cytokine levels, in the ICES group, lacrimal gland cytosolic vesicular density and size exceeded that in the SCOP group. ICES and SCOP induced murine dry eye effects became progressively more severe over a two week period. Subsequently, the disease process stabilized for the next four weeks. ICES induced local effects in the ocular surface, but failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which accounts for less dry eye severity in the ICES model than that in the SCOP model. PMID:25590134

Dynamic ocular surface and lacrimal gland changes induced in experimental murine dry eye.

PubMed

Xiao, Bing; Wang, Yu; Reinach, Peter S; Ren, Yueping; Li, Jinyang; Hua, Shanshan; Lu, Huihui; Chen, Wei

2015-01-01

Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjögren's Syndrome or increased tear film evaporation despite normal lacrimal gland function. To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period. Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an Intelligently Controlled Environmental System (ICES). Sixty mice were housed in ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal environment and received subcutaneous injections of scopolamine hydrobromide (SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal environment and received no treatment. Corneal fluorescein staining along with corneal MMP-9 and caspase-3 level measurements were performed in parallel with the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-β2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light and transmission electron microscopy studies evaluated LGs cytoarchitectural changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2 weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland proinflammatory cytokine level increases were much lower than those in the SCOP group. In accord with the lower proinflammatory cytokine levels, in the ICES group, lacrimal gland cytosolic vesicular density and size exceeded that in the SCOP group. ICES and SCOP induced murine dry eye effects became progressively more severe over a two week period. Subsequently, the disease process stabilized for the next four weeks. ICES induced local effects in the ocular surface, but failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which accounts for less dry eye severity in the ICES model than that in the SCOP model.

MUC19 expression in human ocular surface and lacrimal gland and its alteration in Sjögren syndrome patients.

PubMed

Yu, D F; Chen, Y; Han, J M; Zhang, H; Chen, X P; Zou, W J; Liang, L Y; Xu, C C; Liu, Z G

2008-02-01

This study investigated the expression of MUC19, a newly discovered gel-forming mucin gene, in normal human lacrimal functional unit components and its alteration in Sjögren syndrome patients. Real-time PCR and immunohistochemistry were performed to determine the expression of MUC19 and MUC5AC in human cornea, conjunctiva, and lacrimal gland tissues. Conjunctival impression cytology specimens were collected from normal control subjects and Sjögren syndrome patients for Real-time PCR, PAS staining, and immunohistochemistry assays. In addition, conjunctiva biopsy specimens from both groups were examined for the expression differences of MUC19 and MUC5AC at both mRNA and protein level. The MUC19 mRNA was found to be present in cornea, conjunctiva and lacrimal gland tissues. The immunohistochemical staining of mucins showed that MUC19 was expressed in epithelial cells from corneal, conjunctival, and lacrimal gland tissues. In contrast, MUC5AC mRNA was only present in conjunctiva and lacrimal gland tissues, but not in cornea. Immunostaining demonstrates the co-staining of MUC19 and MUC5AC in conjunctival goblet cells. Consistent with the significant decrease of mucous secretion, both MUC19 and MUC5AC were decreased in conjunctiva of Sjögren syndrome patients compared to normal subjects. Considering the contribution of gel-forming mucins to the homeostasis of the ocular surface, the decreased expression of MUC19 and MUC5AC in Sjögren syndrome patients suggested that these mucins may be involved in the disruption of the ocular surface homeostasis in this disease.

Regulating temporospatial dynamics of morphogen for structure formation of the lacrimal gland by chitosan biomaterials.

PubMed

Hsiao, Ya-Chuan; Yang, Tsung-Lin

2017-01-01

The lacrimal gland is an important organ responsible for regulating tear synthesis and secretion. The major work of lacrimal gland (LG) is to lubricate the ocular surface and maintain the health of eyes. Functional deterioration of the lacrimal gland happens because of aging, diseases, or therapeutic complications, but without effective treatments till now. The LG originates from the epithelium of ocular surface and develops by branching morphogenesis. To regenerate functional LGs, it is required to explore the way of recapitulating and facilitating the organ to establish the intricate and ramified structure. In this study, we proposed an approach using chitosan biomaterials to create a biomimetic environment beneficial to the branching structure formation of developing LG. The morphogenetic effect of chitosan was specific and optimized to promote LG branching. With chitosan, increase in temporal expression and local concentration of endogenous HGF-related molecules creates an environment around the emerging tip of LG epithelia. By efficiently enhancing downstream signaling of HGF pathways, the cellular activities and behaviors were activated to contribute to LG branching morphogenesis. The morphogenetic effect of chitosan was abolished by either ligand or receptor deprivation, or inhibition of downstream signaling transduction. Our results elucidated the underlying mechanism accounting for chitosan morphogenetic effects on LG, and also proposed promising approaches with chitosan to assist tissue structure formation of the LG. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of Epithelial–Mesenchymal Transition in Repair of the Lacrimal Gland after Experimentally Induced Injury

PubMed Central

You, Samantha; Avidan, Orna; Tariq, Ayesha; Ahluwalia, Ivy; Stark, Paul C.; Kublin, Claire L.

2012-01-01

Purpose. Ongoing studies demonstrate that the murine lacrimal gland is capable of repair after experimentally induced injury. It was recently reported that repair of the lacrimal gland involved the mobilization of mesenchymal stem cells (MSCs). These cells expressed the type VI intermediate filament protein nestin whose expression was upregulated during the repair phase. The aim of the present study was to investigate the roles of vimentin, a type III intermediate filament protein and a marker of epithelial–mesenchymal transition (EMT) in repair of the lacrimal gland. Methods. Injury was induced by direct injection of interleukin (IL)-1 into the exorbital lacrimal gland. MSCs were prepared from injured glands using tissue explants. Expression of vimentin and the transcription factor Snai1, a master regulator of EMT, was determined by RT-PCR, Western blotting analysis, and immunofluorescence. Results. These data show that vimentin expression, at both the mRNA and the protein levels, was upregulated during the repair phase (2–3 days postinjury) and returned to the control level when repair ended. Temporal expression of Snai1 mirrored that of vimentin and was localized in cell nuclei. Cultured MSCs isolated from injured lacrimal glands expressed Snai1 and vimentin alongside nestin and alpha smooth muscle actin (another biomarker of EMT). There was a strong positive correlation between Snai1 expression and vimentin expression. Conclusions. It was found that EMT is induced during repair of the lacrimal gland to generate MSCs to initiate repair, and that mesenchymal–epithelial transition is then activated to form acinar and ductal epithelial cells. PMID:22025566

Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients

PubMed Central

Kawashima, Motoko; Maida, Yoshiko; Kamoi, Mizuka; Ogawa, Yoko; Shimmura, Shigeto; Masutomi, Kenkichi; Tsubota, Kazuo

2011-01-01

Purpose Indicators of aging such as disruption of telomeric function due to shortening may be more frequent in dysfunctional lacrimal gland. The aims of this study were to 1) determine the viability of quantitative fluorescence in situ hybridization of telomeres (telo-FISH) for the assessment of telomere length in lacrimal gland in Sjögren and non- Sjögren syndrome patients; and 2) investigate the relationship between progenitor cell markers and telomere length in both groups. Methods Quantitative fluorescence in situ hybridization with a peptide nucleic acid probe complementary to the telomere repeat sequence was performed on frozen sections from human lacrimal gland tissues. The mean fluorescence intensity of telomere spots was automatically quantified by image analysis as relative telomere length in lacrimal gland epithelial cells. Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed. Results Telomere intensity in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02). Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1–3 acinar cells in each acinar unit and continuously in the basal layer of duct cells. In contrast, in the Sjögren syndrome group, p63 and nucleostemin showed a lower level of expression. ABCG2 was expressed in acinar cells in both sjogren and non-Sjogren syndrome. Conclusions The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome. PMID:21655359

Common T cell receptor clonotype in lacrimal glands and labial salivary glands from patients with Sjögren's syndrome.

PubMed Central

Matsumoto, I; Tsubota, K; Satake, Y; Kita, Y; Matsumura, R; Murata, H; Namekawa, T; Nishioka, K; Iwamoto, I; Saitoh, Y; Sumida, T

1996-01-01

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lacrimal and salivary glands leading to symptomatic dry eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lacrimal glands and labial salivary glands are CD4 positive alphabeta T cells. To analyze the pathogenesis of T cells infiltrating into lacrimal and labial salivary glands, we examined T cell clonotype of these cells in both glands from four SS patients using PCR-single-strand conformation polymorphism (SSCP) and a sequencing method. SSCP analysis showed that some infiltrating T cells in both glands expand clonally, suggesting that the cells proliferate by antigen-driven stimulation. Intriguingly, six to sixteen identical T cell receptor (TCR) Vbeta genes were commonly found in lacrimal glands and labial salivary glands from individual patients. This indicates that some T cells infiltrating into both glands recognize the shared epitopes on autoantigens. Moreover, highly conserved amino acid sequence motifs were found in the TCR CDR3 region bearing the same TCR Vbeta family gene from four SS patients, supporting the notion that the shared epitopes on antigens are limited. In conclusion, these findings suggest that some autoreactive T cells infiltrating into the lips and eyes recognized restricted epitopes of a common autoantigen in patients with SS. PMID:8621782

Salivation induced better lacrimal gland function in dry eyes.

PubMed

Pramanik, T; Ghising, R

2009-12-01

The dry eye syndrome is a common eye symptom causing blurry vision. To meet the demand of the modem world students and professionals are compelled to expose themselves to the computer screen for long stretch of time, which is one of the causes of dry eye. It is not always feasible to instil eyes with artificial tears time to time to protect them from dryness. Rather to adopt any simple physiological process associated with optimum lacrimation is a better option to keep eyes moist during computer works. Volunteers (n = 22) having mild dry eyes participated in this study. Tear production was assessed by Schirmer test by keeping Schirmer strip on ocular surface for 5 minutes and recording the length of the moistened area. Then the subject was allowed to keep a piece of lopsy candy (a sour fruit pulp mixed with sugar that is sweet and sour in taste) in mouth for 5 minutes that caused salivation. During salivation, again tear production was assessed. [It was standardized in such a way that, the length of the moistened strip will be 25 - 30 mm for normal eyes, 15 - 10 mm for dry eye, 06 - 10 mm for mild dry eye, 02 - 05 mm for moderate dryness and 00 - 01 mm for severe dry eye.] Tear production was found to be increased significantly (supported by increased length of moistened area of Schirmer strip) during salivation especially in dry eye in all volunteers. The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins; secretion of which are under tight neural control. Anticholinergic agents play an important role in ocular dryness because of hypo-secretion. The sensory root of facial nucleus contains efferent preganglionic parasympathetic fibers for submandibular and sublingual salivary gland and lacrimal gland. The sensory root conveys gustatory fibers from the presulcul area (anterior two-third) of the tongue via the chorda tympani and via the palatine and greater petrosal nerve, taste fibers from the soft palate; it also carries preganglionic (secretomotor) innervations of the submandibular and sublingual salivary gland, lacrimal gland and gland of nasal and palatine mucosa. The taste sensation from the anterior two-third of the tongue, carried by the seventh cranial nerve, a nerve, parasympathetic in nature that contains efferent preganglionic fibers to lacrimal gland. Being stimulated, seventh cranial nerve helps in secretion of tear from the lacrimal glands and gives a sense of relief to the persons facing the problem of mild dryness of eyes.

A rare case of late solitary vertebral metastasis from an adenoid cystic carcinoma of the lacrimal gland.

PubMed

Ahmed, Awaiz; Rajankulam Ganesan, Satish Kannan; Haleem, Shahnawaz; Nicoll, James

2017-06-13

Adenoid cystic carcinoma of the lacrimal gland is one among the common malignancies affecting the lacrimal gland. However, overall, it is a rare condition. It has a rather poor prognosis with local recurrence and distant haematological metastasis which are invariably multiple. We present a rare case of a 51-year-old woman who presented with localised lower thoracic pain with collapse of the T10 vertebral body, which turned out be a solitary late metastasis from her previously treated lacrimal gland tumour. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Altered morphology and function of the lacrimal functional unit in protein kinase C{alpha} knockout mice.

PubMed

Chen, Zhuo; Li, Zhijie; Basti, Surendra; Farley, William J; Pflugfelder, Stephen C

2010-11-01

Protein kinase C (PKC) α plays a major role in the parasympathetic neural stimulation of lacrimal gland (LG) secretion. It also has been reported to have antiapoptotic properties and to promote cell survival. Therefore, the hypothesis for the present study was that PKCα knockout ((-/-)) mice have impaired ocular surface-lacrimal gland signaling, rendering them susceptible to desiccating stress and impaired corneal epithelial wound healing. In this study, the lacrimal function unit (LFU) and the stressed wound-healing response were examined in PKCα(-/-) mice. In PKCα(+/+) control mice and PKCα(-/-) mice, tear production, osmolarity, and clearance rate were evaluated before and after experimental desiccating stress. Histology and immunofluorescent staining of PKC and epidermal growth factor were performed in tissues of the LFU. Cornified envelope (CE) precursor protein expression and cell proliferation were evaluated. The time course of healing and degree of neutrophil infiltration was evaluated after corneal epithelial wounding. Compared with the PKCα(+/+) mice, the PKCα(-/-) mice were noted to have significantly increased lacrimal gland weight, with enlarged, carbohydrate-rich, PAS-positive acinar cells; increased corneal epithelia permeability, with reduced CE expression; and larger conjunctival epithelial goblet cells. The PKCα(-/-) mice showed more rapid corneal epithelial healing, with less neutrophil infiltration and fewer proliferating cells than did the PKCα(+/+) mice. The PKCα(-/-) mice showed lower tear production, which appeared to be caused by impaired secretion by the LG and conjunctival goblet cells. Despite their altered tear dynamics, the PKCα(-/-) mice demonstrated more rapid corneal epithelial wound healing, perhaps due to decreased neutrophil infiltration.

Isolation and Propagation of Mesenchymal Stem Cells from the Lacrimal Gland

PubMed Central

You, Samantha; Kublin, Claire L.; Avidan, Orna; Miyasaki, David

2011-01-01

Purpose. Previously, it was reported that the murine lacrimal gland is capable of repair after experimentally induced injury and that the number of stem/progenitor cells was increased during the repair phase (2–3 days after injury). The aim of the present study was to determine whether these cells can be isolated from the lacrimal gland and propagated in vitro. Methods. Lacrimal gland injury was induced by injection of interleukin (IL)-1, and injection of saline vehicle served as control. Two and half days after injection, the lacrimal glands were removed and used to prepare explants or acinar cells for tissue culture. Cells derived from the explants and the acinar cells were grown in DMEM supplemented with 10% fetal bovine serum. Cells were stained for the stem cells markers, nestin, vimentin, ABCG2, and Sca-1. Cell proliferation was measured using an antibody against Ki67 or a cell-counting kit. The adipogenic capability of these cells was also tested in vitro. Results. Results show that nestin-positive cells can be isolated from IL-1–injected, but not saline-injected, lacrimal glands. A population of nestin-positive cells was also positive for vimentin, an intermediate filament protein expressed by mesenchymal cells. In addition, cultured cells expressed two other markers of stem cells, ABCG2 and Sca-1. These cells proliferated in vitro and can be induced to form adipocytes, attesting to their mesenchymal stem cell property. Conclusions. Murine lacrimal glands contain mesenchymal stem cells that seem to play a pivotal role in tissue repair. PMID:21178145

GCDFP-15, AR, and Her-2 as biomarkers for primary ductal adenocarcinoma of the lacrimal gland: a Chinese case and literature review

PubMed Central

Zhu, Miao-Miao; Cui, Hong-Guang; Teng, Xiao-Dong

2015-01-01

Purpose Primary ductal adenocarcinoma (PDA) of the lacrimal gland is a rare malignant epithelial tumor, and its clinicopathological characteristics are still unclear. This study aimed to report a novel case of PDA of the lacrimal gland in the People’s Republic of China, as well as to determine its histopathological and immunohistochemical characteristics to support early diagnosis and direct further therapy. Patient and methods Clinical data (including ocular examination, computed tomography, magnetic resonance imaging, positron emission tomography, mammography, and serum tumor marker examination) and treatment of a 49-year-old woman with a left lacrimal gland mass, which was diagnosed as PDA of the lacrimal gland, were reported. Histopathological and immunohistochemical studies were performed. Eleven papers regarding this uncommon neoplasm were reviewed. Results Histopathologically, most of the tumor cells featured abundant granular eosinophilic cytoplasm, while few of them had a frothy appearance. The mass showed breast ductal carcinoma-like structural features, which most commonly demonstrated central necrosis, while less of these features showed cord-like infiltration. Immunohistochemically, the tumor cells were positive for GCDFP-15, CK 18 (++), AR (90%), Her-2 (+++), P53 (100%), and Ki-67 (with a proliferation index approximately 60%), while they were negative for ER, PR, P63, calponin, and CD 117. Conclusion This was the first Chinese case of PDA of the lacrimal gland that had been reported. We suggested that GCDFP-15, AR, and Her-2 should be tested as biomarkers for ductal adenocarcinoma of lacrimal gland to confirm diagnosis, guide therapy, and further predict prognosis. PMID:25999735

Detection of BrdU-label Retaining Cells in the Lacrimal Gland: Implications for Tissue Repair

PubMed Central

You, Samantha; Tariq, Ayesha; Kublin, Claire L.; Zoukhri, Driss

2011-01-01

The purpose of the present study was to determine if the lacrimal gland contains 5-bromo-2’-deoxyuridine (BrdU)-label retaining cells and if they are involved in tissue repair. Animals were pulsed daily with BrdU injections for 7 consecutive days. After a chase period of 2, 4, or 12 weeks, the animals were sacrificed and the lacrimal glands were removed and processed for BrdU immunostaining. In another series of experiments, the lacrimal glands of 12-week chased animals were either left untreated or were injected with interleukin 1 (IL-1) to induce injury. Two and half day post-injection, the lacrimal glands were removed and processed for BrdU immunostaining. After 2 and 4 week of chase period, a substantial number of lacrimal gland cells were BrdU+ (11.98 ± 1.84 and 7.95 ± 1.83 BrdU+ cells/mm2, respectively). After 12 weeks of chase, there was a 97% decline in the number of BrdU+ cells (0.38 ± 0.06 BrdU+ cells/mm2), suggesting that these BrdU-label retaining cells may represent slow-cycling adult stem/progenitor cells. In support of this hypothesis, the number of BrdU labeled cells increased over 7-fold during repair of the lacrimal gland (control: 0.41 ± 0.09 BrdU+ cells/mm2, injured: 2.91 ± 0.62 BrdU+ cells/mm2). Furthermore, during repair, among BrdU+ cells 58.2 ± 3.6 % were acinar cells, 26.4 ± 4.1% were myoepithelial cells, 0.4 ± 0.4% were ductal cells, and 15.0 ± 3.0% were stromal cells. We conclude that the murine lacrimal gland contains BrdU-label retaining cells that are mobilized following injury to generate acinar, myoepithelial and ductal cells. PMID:22101331

Isolated lacrimal gland involvement in Rosai-Dorfman-Destombes disease

PubMed Central

Bhalla, Sunita; Srivastava, Amit

2008-01-01

Rosai-Dorfman-Destombes (sinus histiocytosis with massive lymphadenopathy) disease is an uncommon disease characterized by benign proliferation of histiocytes, with painless lymph node enlargement and frequent extranodal disease. Orbital involvement occurs in 9-11% of cases. However, isolated Rosai- Dorfman-Destombes disease of the lacrimal gland without any systemic involvement is very rare with only three case reports. We describe here one such young male patient with unilateral lacrimal gland swelling. Excision biopsy revealed almost complete replacement of the lacrimal gland by lymphocytes, plasma cells and large pale histiocytes. The latter exhibited emperipolesis and stained positive for S-100 and CD68 on immunohistochemistry. Patient is well and has no other manifestation or recurrence of the disease during a follow-up of 24 months. PMID:18974525

Vasoactive intestinal polypeptide (VIP) innervation of the human eyelid glands.

PubMed

Seifert, P; Spitznas, M

1999-06-01

This study was conducted to obtain morphological proof of innervating nerve fibres in the glands of the human eyelid (accessory lacrimal glands of Wolfring, meibomian glands, goblet cells, glands of Zeis, glands of Moll, sweat glands, glands of lanugo hair follicles) and identification of the secretomotorically active neuropeptide vasoactive intestinal polypeptide (VIP) as a common transmitter. Epoxy-embedded ultrathin sections of tissue samples from human eyelids were studied using electron microscopy. Paraffin sections fixed in Bouin-Hollande solution were immunostained with rabbit antiserum against VIP. With the electron microscope we were able to identify nerves in the glandular stroma of all the glands examined with the exception of goblet cells. Intraepithelial single axons were only seen in the parenchyma of Wolfring glands. The morphological findings corresponded with the immunological finding of VIP-positive, nerve-like structures in the same locations, with the exception of lanugo hair follicle glands, and goblet cells. Our findings indicate that the glands of the eyelids and main lacrimal gland represent a functional unit with VIP as a possible common stimulating factor. Copyright 1999 Academic Press.

[Structuro-functional units of the salivary and lacrimal glands].

PubMed

Kostilenko, Iu P; Mysliuk, I V; Deviatkin, E A

1986-09-01

By means of the multilayer graphic and plastic reconstruction methods using series of semithin sections, spatial tridimensional organization of the epithelial complexes and blood microcirculatory bed in the rat palatal salivary glands and the lacrimal gland of the human newborn have been studied. Since their ducts serve not only for discharging their secrete into the external medium, but also for accumulation (as collectors), the sublobular unit--adenomere should be referred to as a part of elementary level of organization of the epithelial complexes. The adenomere has in its composition a collecting centrally situating duct. However, while studying structure of the blood microcirculatory bed, it is found out that there is not any strict territorial correspondence between its functional units and structural units of the glandular epithelium. Nevertheless, giving a great importance to a tight syntopic connection of the collecting ducts of the adenomeres with the postcapillary venules (that belong to filtrating microvessels), these are sublobular units--adenomeres that are distinguished as structural-functional units in the glands.

Altered Morphology and Function of the Lacrimal Functional Unit in Protein Kinase Cα Knockout Mice

PubMed Central

Chen, Zhuo; Li, Zhijie; Basti, Surendra; Farley, William J.

2010-01-01

Purpose. Protein kinase C (PKC) α plays a major role in the parasympathetic neural stimulation of lacrimal gland (LG) secretion. It also has been reported to have antiapoptotic properties and to promote cell survival. Therefore, the hypothesis for the present study was that PKCα knockout (−/−) mice have impaired ocular surface–lacrimal gland signaling, rendering them susceptible to desiccating stress and impaired corneal epithelial wound healing. In this study, the lacrimal function unit (LFU) and the stressed wound-healing response were examined in PKCα−/− mice. Methods. In PKCα+/+ control mice and PKCα−/− mice, tear production, osmolarity, and clearance rate were evaluated before and after experimental desiccating stress. Histology and immunofluorescent staining of PKC and epidermal growth factor were performed in tissues of the LFU. Cornified envelope (CE) precursor protein expression and cell proliferation were evaluated. The time course of healing and degree of neutrophil infiltration was evaluated after corneal epithelial wounding. Results. Compared with the PKCα+/+ mice, the PKCα−/− mice were noted to have significantly increased lacrimal gland weight, with enlarged, carbohydrate-rich, PAS-positive acinar cells; increased corneal epithelia permeability, with reduced CE expression; and larger conjunctival epithelial goblet cells. The PKCα−/− mice showed more rapid corneal epithelial healing, with less neutrophil infiltration and fewer proliferating cells than did the PKCα+/+ mice. Conclusions. The PKCα−/− mice showed lower tear production, which appeared to be caused by impaired secretion by the LG and conjunctival goblet cells. Despite their altered tear dynamics, the PKCα−/− mice demonstrated more rapid corneal epithelial wound healing, perhaps due to decreased neutrophil infiltration. PMID:20505191

Regional differences in rat conjunctival ion transport activities

PubMed Central

Yu, Dongfang; Thelin, William R.; Rogers, Troy D.; Stutts, M. Jackson; Randell, Scott H.; Grubb, Barbara R.

2012-01-01

Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na+ transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface. PMID:22814399

Regional differences in rat conjunctival ion transport activities.

PubMed

Yu, Dongfang; Thelin, William R; Rogers, Troy D; Stutts, M Jackson; Randell, Scott H; Grubb, Barbara R; Boucher, Richard C

2012-10-01

Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na(+) transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface.

Identification of P2X3 and P2X7 Purinergic Receptors Activated by ATP in Rat Lacrimal Gland

PubMed Central

Vrouvlianis, Joanna; Scott, Rachel; Dartt, Darlene A.

2011-01-01

Purpose. To identify the type of purinergic receptors activated by adenosine triphosphate (ATP) in rat lacrimal gland and to determine their role in protein secretion. Methods. Purinergic receptors were identified by RT-PCR, Western blot analysis, and immunofluorescence techniques. Acini from rat lacrimal gland were isolated by collagenase digestion. Acini were incubated with the fluorescence indicator fura-2 tetra-acetoxylmethyl ester, and intracellular [Ca2+] ([Ca2+]i) was determined. Protein secretion was measured by fluorescence assay. Results. The authors previously showed that P2X7 receptors were functional in the lacrimal gland. In this study, they show that P2X1–4, and P2X6receptors were identified in the lacrimal gland by RT-PCR, Western blot, and immunofluorescence analyses. P2X5 receptors were not detected. ATP increased [Ca2+]i and protein secretion in a concentration-dependent manner. Removal of extracellular Ca2+ significantly reduced the ATP-stimulated increase in [Ca2+]i. Repeated applications of ATP caused desensitization of the [Ca2+]i response. Incubation with the P2X1 receptor inhibitor NF023 did not alter ATP-stimulated [Ca2+]i. Incubation with zinc, which potentiates P2X2 and P2X4 receptor responses, or lowering the pH to 6.8, which potentiates P2X2 receptor responses, did not alter the ATP-stimulated [Ca2+]i. P2X3 receptor inhibitors A-317491 and TNP-ATP significantly decreased ATP-stimulated [Ca2+]i and protein secretion, whereas the P2X3 receptor agonist α,β methylene ATP significantly increased them. The P2X7 receptor inhibitor A438079 had no effect on ATP-stimulated [Ca2+]i at 10−6 M but did have an effect at 10−4 M. Conclusions. Purinergic receptors P2X1–4 and P2X6 are present in the lacrimal gland. ATP uses P2X3 and P2X7 receptors to stimulate an increase in [Ca2+]i and protein secretion. PMID:21421865

Did Androgen-Binding Protein Paralogs Undergo Neo- and/or Subfunctionalization as the Abp Gene Region Expanded in the Mouse Genome?

PubMed Central

Karn, Robert C.; Chung, Amanda G.; Laukaitis, Christina M.

2014-01-01

The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding proteins are expressed at very low levels compared to those transcripts with proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution. PMID:25531410

Did androgen-binding protein paralogs undergo neo- and/or Subfunctionalization as the Abp gene region expanded in the mouse genome?

PubMed

Karn, Robert C; Chung, Amanda G; Laukaitis, Christina M

2014-01-01

The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding proteins are expressed at very low levels compared to those transcripts with proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution.

Long-Term Outcomes of Eye-Sparing Surgery for Adenoid Cystic Carcinoma of Lacrimal Gland.

PubMed

Han, Jisang; Kim, Yoon-Duck; Woo, Kyung In; Sobti, Deepak

This study's primary purpose is to assess the long-term outcomes of patients who have undergone eye-sparing surgery and adjuvant radiotherapy for adenoid cystic carcinoma of the lacrimal gland. In this retrospective analysis, clinical records were reviewed of all patients diagnosed with adenoid cystic carcinoma of the lacrimal gland, at a single institution, between March 1998 and November 2012. Ten patients were identified as having undergone eye-sparing surgery and adjuvant radiotherapy for adenoid cystic carcinoma of the lacrimal gland. Preoperative radiographic findings, treatment modalities, histological results, and patient outcomes were analyzed. There were 6 male and 4 female patients. The patients' tumors were staged according to the 8th American Joint Committee on Cancer staging system, and were as follows: 1 patient was classified as T1aN0M0; 6 patients were classified as T2aN0M0; 1 patient was classified as T2cN0M0; 2 patients were classified as T3aN0M0. All patients had a histologically confirmed diagnosis of lacrimal gland adenoid cystic carcinoma, which was confined to the orbit, and was without extension into adjacent bone marrow or other organs. All patients underwent eye-sparing tumor excision followed by postoperative radiotherapy, with a median dose of 6000 cGy (range: 5000-6600 cGy). At the last follow up, 8 patients were alive without evidence of disease. One patient was deceased at 58 months post-surgery, due to esophageal carcinoma; this was unrelated to the lacrimal gland tumor. The final patient experienced tumor recurrence in the medial orbit 53 months post-surgery, and exenteration was performed. This patient was alive, without disease recurrence, at 90 months following exenteration. The median follow-up time was 89.5 months (range: 37-217 months). Systemic metastasis did not occur in any patient. Eye-sparing surgery and adjuvant radiotherapy have demonstrated favorable local control and long-term survival outcomes in patients with orbit-confined lacrimal gland adenoid cystic carcinoma. Consequently, eye-sparing surgery with adjuvant radiotherapy can be considered as a viable treatment option for orbit-confined lacrimal gland adenoid cystic carcinoma.

Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system.

PubMed

Knop, E; Knop, N

2001-03-01

Mucosa-associated lymphoid tissue (MALT) specifically protects mucosal surfaces. In a previous study of the human conjunctiva, evidence was also found for the presence of MALT in the lacrimal sac. The present study, therefore, aims to investigate its morphology and topographical distribution in the human lacrimal drainage system. Lacrimal drainage systems (n = 51) obtained from human cadavers were investigated by clearing flat wholemounts or by serial sections of tissue embedded in paraffin, OCT compound, or epoxy resin. These were further analyzed by histology, immunohistochemistry, and electron microscopy. All specimens showed the presence of lymphocytes and plasma cells as a diffuse lymphoid tissue in the lamina propria, together with intraepithelial lymphocytes and occasional high endothelial venules (HEV). It formed a narrow layer along the canaliculi that became thicker in the cavernous parts. The majority of lymphocytes were T cells, whereas B cells were interspersed individually or formed follicular centers. T cells were positive for CD8 and the human mucosa lymphocyte antigen (HML-1). Most plasma cells were positive for IgA and the overlying epithelium expressed its transporter molecule secretory component (SC). Basal mucous glands were present in the lacrimal canaliculi and in the other parts accompanied by alveolar and acinar glands, all producing IgA-rich secretions. Primary and secondary lymphoid follicles possessing HEV were present in about half of the specimens. The term lacrimal drainage-associated lymphoid tissue (LDALT) is proposed here to describe the lymphoid tissue that is regularly present and belongs to the common mucosal immune system and to the secretory immune system. It is suggested that it may form a functional unit together with the lacrimal gland and conjunctiva, connected by tear flow, lymphocyte recirculation, and probably the neural reflex arc, and play a major role in preserving ocular surface integrity.

Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome

PubMed Central

2011-01-01

Introduction In Sjögren's syndrome, keratoconjunctivitis sicca (dry eye) is associated with infiltration of lacrimal glands by leukocytes and consequent losses of tear-fluid production and the integrity of the ocular surface. We investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR) pathway on lacrimal-gland pathology in the NOD mouse model of Sjögren's syndrome. Methods Male NOD mice were treated for up to ten weeks with an antagonist, LTBR-Ig, or control mouse antibody MOPC-21. Extra-orbital lacrimal glands were analyzed by immunohistochemistry for high endothelial venules (HEV), by Affymetrix gene-array analysis and real-time PCR for differential gene expression, and by ELISA for CXCL13 protein. Leukocytes from lacrimal glands were analyzed by flow-cytometry. Tear-fluid secretion-rates were measured and the integrity of the ocular surface was scored using slit-lamp microscopy and fluorescein isothiocyanate (FITC) staining. The chemokine CXCL13 was measured by ELISA in sera from Sjögren's syndrome patients (n = 27) and healthy controls (n = 30). Statistical analysis was by the two-tailed, unpaired T-test, or the Mann-Whitney-test for ocular integrity scores. Results LTBR blockade for eight weeks reduced B-cell accumulation (approximately 5-fold), eliminated HEV in lacrimal glands, and reduced the entry rate of lymphocytes into lacrimal glands. Affymetrix-chip analysis revealed numerous changes in mRNA expression due to LTBR blockade, including reduction of homeostatic chemokine expression. The reduction of CXCL13, CCL21, CCL19 mRNA and the HEV-associated gene GLYCAM-1 was confirmed by PCR analysis. CXCL13 protein increased with disease progression in lacrimal-gland homogenates, but after LTBR blockade for 8 weeks, CXCL13 was reduced approximately 6-fold to 8.4 pg/mg (+/- 2.7) from 51 pg/mg (+/-5.3) in lacrimal glands of 16 week old control mice. Mice given LTBR blockade exhibited an approximately two-fold greater tear-fluid secretion than control mice (P = 0.001), and had a significantly improved ocular surface integrity score (P = 0.005). The mean CXCL13 concentration in sera from Sjögren's patients (n = 27) was 170 pg/ml, compared to 92.0 pg/ml for sera from (n = 30) healthy controls (P = 0.01). Conclusions Blockade of LTBR pathways may have therapeutic potential for treatment of Sjögren's syndrome. PMID:22044682

Patterns of innervation of the lacrimal gland with clinical application.

PubMed

Scott, Gabriel; Balsiger, Heather; Kluckman, Matthew; Fan, Jerry; Gest, Thomas

2014-11-01

Parasympathetic stimulation of the lacrimal gland is responsible for tear production, and this innervation originates from fibers conveyed in the facial nerve. After synapse in the pterygopalatine ganglion, postsynaptic parasympathetic fibers travel within the zygomatic and zygomaticotemporal nerves (ZTN) into the orbit. As described in most anatomy texts, ZTN communicates with the lacrimal nerve (LN) posterior to the gland and then secretomotor fibers enter the gland. This study was performed to gain a better understanding of the innervation of the lacrimal gland. Seventeen cadaver heads were bisected for a total of 34 sides, which then underwent dissection of the superolateral orbital region to observe the course for the LN and ZTN. Three variations of the course of the LN and ZTN were found. In 20 (60.6%) dissections it was documented that the ZTN entered directly into the lacrimal gland with no communication with the LN. In 12 (36.4%) of the bisected heads, ZTN had both a direct connection into the gland and a communicating branch with the LN. In only one (3.0%) bisected head, ZTN communicated with the LN before entering the gland as it is commonly described in anatomy texts. Our study reveals that the ZTN usually takes a different course than is classically described in most anatomy textbooks. A greater understanding of the typical course these nerves take may help surgeons identify them more easily and avoid damaging them. © 2014 Wiley Periodicals, Inc.

Comparison of botulinum toxin-A injection in lacrimal gland and conjunctivodacryocystorhinostomy for treatment of epiphora due to proximal lacrimal system obstruction

PubMed Central

Kaynak, P; Karabulut, G O; Ozturker, C; Fazil, K; Arat, Y O; Perente, I; Akar, S; Yilmaz, O F; Demirok, A

2016-01-01

Purpose To investigate and compare the efficacy of botulinum toxin-A injection in the lacrimal gland and conjunctivodacryocystorhinostomy surgery for the treatment of epiphora caused by proximal lacrimal system obstruction. Methods Charts of the patients with proximal canalicular obstruction who had undergone conjunctivodacryocystorhinostomy with permanent tube insertion (18 patients, group 1) or 4 units of botulinum toxin-A injection in the palpebral lobe of the lacrimal gland (20 patients, group 2) were reviewed retrospectively. The upper lacrimal system obstruction was diagnosed by lacrimal system irrigation. Schirmer-1 test and Munk epiphora grading for evaluation of epiphora were performed before the interventions and on tenth day, first, third, and sixth months after the interventions. Results Improvement of epiphora was statistically significant at all visits when compared with values before injection (P<0.001) in both of groups. When two techniques were compared, difference in degree of epiphora before and after intervention was not statistically significant (P<0.05). In group 2, none of the patients had punctate epitheliopathy, although there was a significant decrease in Schirmer test results (P<0.001, paired t-test). In group 1, 9 cases (50%) had tube dislocation, 4 cases (22.2%) had obstruction, and granuloma formation. Five cases (25%) had ptosis in group 2. Conclusion  Conjunctivodacryocystorhinostomy requires surgical experience, special postoperative care, and multiple revisions. As botulinum toxin-A injection in the lacrimal gland is technically easy, less-invasive, safe, with reversible effects, it can be considered as an alternative treatment in patients with proximal lacrimal system obstruction. PMID:27197871

Cytochrome P450 3A expression and activity in the rabbit lacrimal gland: glucocorticoid modulation and the impact on androgen metabolism.

PubMed

Attar, Mayssa; Ling, Kah-Hiing John; Tang-Liu, Diane D-S; Neamati, Nouri; Lee, Vincent H L

2005-12-01

Cytochrome P450 3A (CYP3A) is an enzyme of paramount importance to drug metabolism. The expression and activity of CYP3A, an enzyme responsible for active androgen clearance, was investigated in the rabbit lacrimal gland. Analysis of CYP3A expression and activity was performed on lacrimal gland tissues obtained from naïve untreated and treated New Zealand White rabbits. For 5 days, treated rabbits received daily administration of vehicle or 0.1% or 1.0% dexamethasone, in the lower cul-de-sac of each eye. Changes in mRNA expression were monitored by real-time RT-PCR. Protein expression was confirmed by Western blot. Functional activity was measured by monitoring the metabolism of CYP3A probe substrates-namely, 7-benzyloxyquinoline (BQ) and [3H]testosterone. Cytochrome P450 heme protein was detected at a concentration of 44.6 picomoles/mg protein, along with its redox partner NADPH reductase and specifically CYP3A6 in the naïve rabbit lacrimal gland. Genes encoding CYP3A6, in addition to the pregnane-X-receptor (PXR) and P-glycoprotein (P-gp) were expressed in the untreated tissue. BQ dealkylation was measured in the naïve rabbit lacrimal gland at a rate of 14 +/- 7 picomoles/mg protein per minute. Changes in CYP3A6, P-gp, and androgen receptor mRNA expression levels were detected after dexamethasone treatment. In addition, dexamethasone treatment resulted in significant increases in BQ dealkylation and CYP3A6-mediated [3H]testosterone metabolism. Concomitant increases in CYP3A6-mediated hydroxylated testosterone metabolites were observed in the treated rabbits. Furthermore, ketoconazole, all-trans retinoic acid, and cyclosporine inhibited CYP3A6 mediated [3H]testosterone 6beta hydroxylation in a concentration-dependent manner, with IC50 ranging from 3.73 to 435 microM. The results demonstrate, for the first time, the expression and activity of CYP3A6 in the rabbit lacrimal gland. In addition, this pathway was shown to be subject to modulation by a commonly prescribed glucocorticoid and can be inhibited by known CYP3A inhibitors.

[The expression of MMP-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland].

PubMed

Zhang, Lei; Zhang, Hong; Song, Guo-xiang; Lin, Ting-ting; Xu, Guang-chang; Zhu, Li-min

2013-01-01

To investigate the expression of matrix metal proteinase (MMP)-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland as well as their relation with biological behaviour of adenoid cystic carcinoma. Experimental study. The research objects were 60 cases of adenoid cystic carcinoma of lacrimal gland which were collected from No.2 Hospital of Tianjin Medical University from January 1991 to Jule 2011. There were 25 males and 35 females aged from 29 to 42 years. Based on histological revision, there were 36 cases of cribriform-tubular subtype and 24 cases of solid subtype. Forty-five cases were primary lesions and 15 cases were recurrent lesions. Ten samples of normal lacrimal gland around polymorphic adenoma were selected as the control group. The expression of CD105, MMP-2 and MMP-9 were evaluated by immunohistochemistry. The microvessel density (MVD) was defined by expression of CD105. One way ANOVA, χ(2)-test and spearman correlation test were used to analyzed the data. The number of MVD [(17.71 ± 5.63)/100 folds field of vision] and the positive rates of MMP-2 (45.0%, 27/60) and MMP-9 (55.0%, 33/60) in the samples of adenoid cystic carcinoma of lacrimal gland were higher than those in the normal lacrimal gland [the number of MVD was (0.70 ± 0.95)/100 folds field of vision, the expressions of MMP-2 and MMP-9 were negative] (t' = 2.039, P < 0.05; χ(2) = 5.550, P < 0.05; χ(2) = 8.315, P < 0.01), the solid subtypes had more MVD [(26.12 ± 5.32)/100 folds field of vision] and higher positive rates of MMP-2 (62.5%, 15/24) and MMP-9 (79.2%, 19/24) than the cribriform-tubular subtypes (t' = 2.060, P < 0.05; χ(2) = 4.950, P < 0.05; χ(2) = 9.439, P < 0.05); the recurrent lesions had more MVD and higher positive rate of MMP-2 and MMP-9 than the primary lesions (t' = 2.129, P < 0.05; χ(2) = 9.899, P < 0.05; χ(2) = 8.103, P < 0.05). The number of MVD in ACC of lacrimal gland patients was correlated with the positive rate of MMP-2 and MMP-9 respectively (rs = 0.636, P < 0.05; rs = 0.524, P < 0.05). The number of MVD and the expression of MMP-2 and MMP-9 are higher level in adenoid cystic carcinoma of lacrimal gland and are significantly correlated with pathological type and recurrence. Detecting the number of MVD and the expression of MMP-2 and MMP-9 may become biological indexes for malignancy, recurrence and metastasis of adenoid cystic carcinoma of lacrimal gland.

Effect of sensory denervation on the structure and physiologic responsiveness of rabbit lacrimal gland.

PubMed

Meneray, M A; Bennett, D J; Nguyen, D H; Beuerman, R W

1998-01-01

This work was conducted to determine the effects of unilateral trigeminal ganglion ablation on lacrimal gland structure and secretory activity. Adult male New Zealand rabbits underwent unilateral thermocoagulation of the ophthalmic division of the trigeminal ganglion. Sensory denervation was affirmed by anatomic inspection of the lesion and transmission electron microscopy (TEM) of the lacrimal gland innervation. Eight to 10 days after the procedure, the intraorbital lacrimal glands were removed from both sides. To compare the physiologic competence of the intact and denervated glands, freshly isolated gland fragments from the paired intact and denervated glands were stimulated with carbachol (100 microM), isoproterenol (10 microM), phorbol-12,13-dibutyrate (PDBu, 10 microM), forskolin (40 microM), or vehicle. Total secreted protein was measured at 30 or 60 min after the establishment of baseline values. Intact and denervated glands also were examined by light and TEM, and the morphologic appearance of the acinar structures as well as the appearance of nerves innervating the gland after denervation were assessed. Similar experiments were conducted with animals that underwent unilateral superior cervical ganglionectomy. Tissues from sensory denervated glands released significantly more protein than did tissues from innervated glands in response to in vitro stimulation by carbachol or isoproterenol but not in response to PDBu or forskolin. Microscopy showed that the acinar cells that had undergone sensory denervation showed a massive accumulation of secretory granules. The secretory granules filled the entire cytoplasmic space and displaced the ellipsoidal nuclei to the extreme periphery. Examination of segments of nerves revealed numerous unmyelinated axons, a few small-diameter myelinated axons, and a large amount of nerve degeneration after sensory denervation. In contrast to the effects of sensory denervation, sympathetic denervation did not alter either the acinar appearance or secretory responsiveness of the gland. Loss of the considerable sensory innervation from the trigeminal ganglion has pronounced effects on the pharmacologic responsiveness and the structure of the lacrimal gland. The effects of sensory innervation on the gland may be mediated through two possible pathways: direct input to the gland or control of the preganglionic parasympathetic pathway.

A Chronic Autoimmune Dry Eye Rat Model with Increase in Effector Memory T Cells in Eyeball Tissue.

PubMed

Hou, Aihua; Bose, Tanima; Chandy, K George; Tong, Louis

2017-06-07

Dry eye disease is a very common condition that causes morbidity and healthcare burden and decreases the quality of life. There is a need for a suitable dry eye animal model to test novel therapeutics to treat autoimmune dry eye conditions. This protocol describes a chronic autoimmune dry eye rat model. Lewis rats were immunized with an emulsion containing lacrimal gland extract, ovalbumin, and complete Freund's adjuvant. A second immunization with the same antigens in incomplete Freund's adjuvant was administered two weeks later. These immunizations were administered subcutaneously at the base of the tail. To boost the immune response at the ocular surface and lacrimal glands, lacrimal gland extract and ovalbumin were injected into the forniceal subconjunctiva and lacrimal glands 6 weeks after the first immunization. The rats developed dry eye features, including reduced tear production, decreased tear stability, and increased corneal damage. Immune profiling by flow cytometry showed a preponderance of CD3 + effector memory T cells in the eyeball.

A Chronic Autoimmune Dry Eye Rat Model with Increase in Effector Memory T Cells in Eyeball Tissue

PubMed Central

Hou, Aihua; Bose, Tanima; Chandy, K. George; Tong, Louis

2017-01-01

Dry eye disease is a very common condition that causes morbidity and healthcare burden and decreases the quality of life. There is a need for a suitable dry eye animal model to test novel therapeutics to treat autoimmune dry eye conditions. This protocol describes a chronic autoimmune dry eye rat model. Lewis rats were immunized with an emulsion containing lacrimal gland extract, ovalbumin, and complete Freund's adjuvant. A second immunization with the same antigens in incomplete Freund's adjuvant was administered two weeks later. These immunizations were administered subcutaneously at the base of the tail. To boost the immune response at the ocular surface and lacrimal glands, lacrimal gland extract and ovalbumin were injected into the forniceal subconjunctiva and lacrimal glands 6 weeks after the first immunization. The rats developed dry eye features, including reduced tear production, decreased tear stability, and increased corneal damage. Immune profiling by flow cytometry showed a preponderance of CD3+ effector memory T cells in the eyeball. PMID:28654074

Anti-Inflammatory Effects of Rebamipide Eyedrop Administration on Ocular Lesions in a Murine Model of Primary Sjögren's Syndrome

PubMed Central

Arakaki, Rieko; Eguchi, Hiroshi; Yamada, Akiko; Kudo, Yasusei; Iwasa, Akihiko; Enkhmaa, Tserennadmid; Hotta, Fumika; Mitamura-Aizawa, Sayaka; Mitamura, Yoshinori; Hayashi, Yoshio; Ishimaru, Naozumi

2014-01-01

Background Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown. Methods and Finding Reb eyedrops were administered to the murine model of SS aged 4–8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment. Conclusion Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces. PMID:24866156

Sarcoidosis of the lacrimal gland as a first manifestation.

PubMed

Peralta-Gómez, M Y; Ávila-Ocampo, K A; Huerta-Velázquez, S; Rivera-Salgado, M I

2018-04-01

The first manifestation of sarcoidosis is usually at the pulmonary level. The case is described of a 40-year-old female patient, who presented with an increased volume of the lacrimal gland and mechanical ptosis of upper left eyelid as the first expression of this disease. The diagnosis of systemic sarcoidosis with primary presentation of the lacrimal gland was made after performing several immunological studies with negative results, imaging studies, and taking of glandular and lymph node biopsies. A favourable response was achieved with oral methotrexate treatment. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Efficacy of laser stimulation of the lacrimal gland and collagen punctual occlusion in the treatment of dry-eye syndrome

NASA Astrophysics Data System (ADS)

Switka-Wieclawska, Iwona; Kecik, Tadeusz; Ciszewska, Joanna

1997-10-01

In this study we would like to monitor the tear secretion during a 7 day period of temporary intracanalicular occlusion and laser stimulation of lacrimal gland in a small group of female suffering of dry eye syndrome.

[Functional tear production indices in thyroid eye disease].

PubMed

Safonova, T N; Likhvantseva, V G; Gontiurova, O A; Rudenko, E I; Vygodin, V A

2013-01-01

Analysis of functional tear production indices in patients with Grave's disease and thyroid eye disease confirmed lacrimal gland involvement in inflammatory autoimmune process. Close direct correlation was found between tear production and main disease characteristics - severity and activity.

Computed tomographic imaging characteristics of the normal canine lacrimal glands

PubMed Central

2014-01-01

Background The canine lacrimal gland (LG) and accessory lacrimal gland of the third eyelid (TEG) are responsible for production of the aqueous portion of the precorneal tear film. Immune-mediated, toxic, neoplastic, or infectious processes can affect the glands directly or can involve adjacent tissues, with secondary gland involvement. Disease affecting these glands can cause keratoconjunctivitis sicca, corneal ulcers, and loss of vision. Due to their location in the orbit, these small structures are difficult to evaluate and measure, making cross-sectional imaging an important diagnostic tool. The detailed cross-sectional imaging appearance of the LG and TEG in dogs using computed tomography (CT) has not been reported to date. Results Forty-two dogs were imaged, and the length, width, and height were measured and the volume calculated for the LGs & TEGs. The glands were best visualized in contrast-enhanced CT images. The mean volume of the LG was 0.14 cm3 and the TEG was 0.1 cm3. The mean height, width, and length of the LG were, 9.36 mm, 4.29 mm, and 9.35 mm, respectively; the corresponding values for the TEG was 2.02 mm, 9.34 mm, and 7.90 mm. LG and TEG volume were positively correlated with body weight (p < 0.05). Conclusions Contrast-enhanced CT is a valuable tool for noninvasive assessment of canine lacrimal glands. PMID:24886364

What causes dryness in Sjögren's syndrome patients and how can it be targeted?

PubMed

Pflugfelder, Stephen C

2014-04-01

Concepts regarding what causes dryness in Sjögren's syndrome have evolved over the past decade. Inflammation in the lacrimal functional unit contributes to development of dry eye by causing dysfunction and even death of tear secreting epithelium in the lacrimal gland and conjunctiva that alters tear composition and stability. Disease-relevant inflammatory mediators have been identified and therapies targeting these mediators are beginning to emerge.

Granulomatosis with polyangiitis confined to lacrimal gland, a case report.

PubMed

Zuazo, F; González, M; Abdala, A; Olvera-Morales, O; Monroy, M H; Rodríguez-Reyes, A; Tovilla-Canales, J L; Nava-Castañeda, Á

2017-11-01

A 43 year-old woman consulted due to 2 months of swelling on the superolateral side of the left orbit, with pain and erythema. An excisional biopsy was performed that revealed vasculitis with polyangiitis of the lacrimal gland. A systemic study showed that no other system was compromised. Orbital involvement occurs in up to 60% of patients with granulomatosis with polyangiitis. The involvement of the lacrimal gland is rare and often unilateral. Serological tests are generally negative, both in initial stages, as in localized forms of the disease. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Investigations on the conjunctival goblet cells and the characteristics of the glands associated with the eye in chinchillas (Chinchilla Laniger).

PubMed

Voigt, Susanne; Fuchs-Baumgartinger, Andrea; Egerbacher, Monika; Tichy, Alexander; Nell, Barbara

2012-09-01

To investigate the density and distribution of conjunctival goblet cells (GC) and study the anatomy and microscopic characteristics of glands associated with the eye in chinchillas (Chinchilla Laniger). 12 chinchillas were included in the study. Conjunctiva (divided into four regions), eyelids, and glands were embedded in paraffin wax, sectioned, stained, and analyzed. Highest GC densities were found in the palpebral region of the nasal and temporal conjunctiva of both eyelids (GC index: 25.1-18.2%), and lowest densities, in the bulbar and marginal region of the nasal and temporal conjunctiva of both eyelids (GC index: 1.5-0.0%). Meibomian glands extend along the entire length of both eyelids, and the whole glandular complex broadens toward the temporal canthus. This is macroscopically visible through the conjunctiva. The openings of the Meibomian glands are macroscopically not discernible. The light pink, smooth, and crescent-shaped lacrimal gland lies next to the aforementioned broadened part of the Meibomian glands in the temporal canthus. The whitish, 0.9-cm-long, smooth Harderian gland is firmly attached to the posterior part of the globe and extends nasally from the optic nerve to the equator. Furthermore, chinchillas possess two lacrimal puncta, situated on the inner conjunctival surface of both eyelids near the medial canthus. A pigmented lacrimal canaliculus originates from each punctum. The vestigial nictitating membrane is supported by a hyaline cartilage and is pigmented at its free margin. Chinchillas possess a Harderian gland, a lacrimal gland, and Meibomian glands. The GC density in the nasal and temporal palpebral conjunctiva is higher than in guinea pigs. © 2012 American College of Veterinary Ophthalmologists.

Inflammation in dry eye.

PubMed

Stern, Michael E; Pflugfelder, Stephen C

2004-04-01

Dry eye is a condition of altered tear composition that results from a diseased or dysfunctional lacrimal functional unit. Evidence suggests that inflammation causes structural alterations and/or functional paralysis of the tear-secreting glands. Changes in tear composition resulting from lacrimal dysfunction, increased evaporation and/or poor clearance have pro-inflammatory effects on the ocular surface. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. Anti-inflammatory therapies for dry eye target one or more of the inflammatory mediators/pathways that have been identified in dry eye.

Effect of radioactive iodine therapy on lacrimal gland functions in patients with hyperthyroidism.

PubMed

Aydogan, Fusun; Ayhan Tuzcu, Esra; Aydogan, Akin; Akkucuk, Seckin; Coskun, Mesut; Ustun, Ihsan; Gökçe, Cumali

2014-04-01

Radioactive iodine (RAI) therapy is preferred in the treatment of hyperthyroidism because of its effectiveness, noninvasiveness, and low costs. I has been detected in extrathyroidal tissues, such as in gastric mucosa, salivary glands, and lacrimal glands. To the best of our knowledge, there is no publication concerning the effects of RAI therapy for hyperthyroidism on tear production. In the present study, we evaluated whether or not the lacrimal glands are affected after RAI therapy when compared with pretreatment period. The Schirmer and tear break-up time (TBUT) tests were used to assess 32 eyes of 16 patients with conditions that were diagnosed as hyperthyroidism before and at 3 and 6 months after RAI treatment. In addition, pretreatment values of patients were compared with that of controls. It was evaluated whether or not a correlation exists between the results and the dose or iodine uptake values. There was no significant difference between pretreatment values of Schirmer and TBUT tests obtained in the patient group and those of the control group (P > 0.05). In the patient group, there was a significant difference between the posttreatment and pretreatment values (P < 0.05). There was a positive correlation between uptake values obtained at 24 hours and the values obtained by TBUT and Schirmer tests on both eyes at 3 and 6 months. At 6 months, the uptake value at 24 hours was 28.83 ± 60 for both eyes in patients with TBUT test values less than 10, whereas it was 39.25 ± 7.88 for the right eye and 39.00 ± 6.85 for the left eyes in patients with TBUT test values greater than 10. The difference was statistically significant (P < 0.05). In our study, we concluded that the decrease in mucin and aqueous production occurs due to affected lacrimal glands by RAI therapy; however, this effect is not dose dependent.

Human lacrimal gland mucins.

PubMed

Paulsen, Friedrich; Langer, Gesa; Hoffmann, Werner; Berry, Monica

2004-05-01

The objective of this study was to determine whether the lacrimal gland synthesizes mucins and whether they are changed with age or in cases of dry eye. Expression of mucins in human lacrimal glands was monitored by reverse transcription-polymerase chain reaction analysis. Furthermore, the presence and distribution of MUC1, -2, -4, -5AC, -5B, -6 and -7 in epithelia of the human lacrimal gland and its excretory duct system were assessed with antisera to mucin peptide cores. Thirty normal tissues from cadavers of different ages were tested, plus four with dry eye treated with artificial tears. Expression studies detected mRNAs for mucins MUC1, -4, -5AC, -5B, -6 and -7; whereas the MUC2 message was absent. The message for MUC4 was present in all four cases of dry eye, but only in six out of the 30 normal glands from individuals who did not receive artificial tears. MUC6 mRNA was detected only in about half of the investigated samples. Immunohistochemistry revealed membrane-bound MUC1 at the apical surface of acinar cells, absence of MUC2, MUC5AC associated with goblet cells of excretory ducts, MUC5B and -7 in the cytoplasm of acinar cells, and MUC7 also in epithelial cells of excretory ducts. MUC4 mucin was detected only in those individuals in which message was identified. In dry eyes, MUC5AC and -5B were localized in the same acinar cells; whereas MUC2 and MUC6 were not detectable. Dot-blot analysis clearly revealed increased amounts of MUC4, -5AC, and -5B in the glands of elderly women who received treatment for dry eyes. These results confirm that the human lacrimal gland synthesizes a spectrum of mucins; part of them might be correlated with age. Copyright 2004 Springer-Verlag

Development of lacrimal gland spheroids for lacrimal gland tissue regeneration.

PubMed

Massie, Isobel; Spaniol, Kristina; Barbian, Andreas; Geerling, Gerd; Metzger, Marco; Schrader, Stefan

2018-04-01

Severe dry eye syndrome resulting from lacrimal gland (LG) dysfunction can cause blindness, yet treatments remain palliative. In vitro reconstruction of LG tissue could provide a curative treatment. We aimed to combine epithelial cells with endothelial cells and mesenchymal stem cells (MSCs) to form a 3D functional unit. Epithelial cells and MSCs were isolated from porcine LG; endothelial cells were isolated from human foreskin. MSCs were characterised (flow cytometry and differentiation potential assays). All 3 cell types were combined on Matrigel and spheroid formation observed. Spheroids were characterised [immunohistochemistry (IHC) and transmission electron microscopy] and function assessed (β-hexosaminidase assay). Spheroids were transferred to decellularised jejunum (SIS-Muc) in dynamic cultures for 1 week before further characterisation. MSCs did not express CD31 but expressed CD44 and CD105 and differentiated towards osteogenic and adipogenic lineages. Spheroids formed on Matrigel within 18 hr, contracting to ~10% of the well area (p < .005). IHC revealed presence of all 3 cells within spheroids. Transmission electron microscopy revealed cell-cell contacts and polarisation at the apical surface. In static cultures, function was increased in spheroids cf. monolayer controls (p < .05) but over 72 hr, spheroid function (p < .05), viability (p < .05), and proliferation decreased, whilst apoptosis increased. On SIS-Muc under dynamic culture, however, spheroids continued to proliferate to repopulate SIS-Muc. IHC revealed LG epithelial cells coexpressing pan-cytokeratin and lysozyme, as well as endothelial cells and MSCs and cells remained capable of responding to carbachol (p < .05). These spheroids could form the basis of a regenerative medicine treatment approach for dry eye syndrome. In vivo studies are required to evaluate this further. Copyright © 2017 John Wiley & Sons, Ltd.

Combined model-based and patient-specific dosimetry for 18F-DCFPyL, a PSMA-targeted PET agent.

PubMed

Plyku, Donika; Mena, Esther; Rowe, Steven P; Lodge, Martin A; Szabo, Zsolt; Cho, Steve Y; Pomper, Martin G; Sgouros, George; Hobbs, Robert F

2018-06-01

Prostate-specific membrane antigen (PSMA), a type-II integral membrane protein highly expressed in prostate cancer, has been extensively used as a target for imaging and therapy. Among the available PET radiotracers, the low molecular weight agents that bind to PSMA are proving particularly effective. We present the dosimetry results for 18 F-DCFPyL in nine patients with metastatic prostate cancer. Nine patients were imaged using sequential PET/CT scans at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately 120 min after intravenous administration of 321 ± 8 MBq (8.7 ± 0.2 mCi) of 18 F-DCFPyL. Time-integrated-activity coefficients were calculated and used as input in OLINDA/EXM software to obtain dose estimates for the majority of the major organs. The absorbed doses (AD) to the eye lens and lacrimal glands were calculated using Monte-Carlo models based on idealized anatomy combined with patient-specific volumes and activity from the PET/CT scans. Monte-Carlo based models were also developed for calculation of the dose to two major salivary glands (parotid and submandibular) using CT-based patient-specific gland volumes. The highest calculated mean AD per unit administered activity of 18 F was found in the lacrimal glands, followed by the submandibular glands, kidneys, urinary bladder wall, and parotid glands. The S-values for the lacrimal glands to the eye lens (0.42 mGy/MBq h), the tear film to the eye lens (1.78 mGy/MBq h) and the lacrimal gland self-dose (574.10 mGy/MBq h) were calculated. Average S-values for the salivary glands were 3.58 mGy/MBq h for the parotid self-dose and 6.78 mGy/MBq h for the submandibular self-dose. The resultant mean effective dose of 18 F-DCFPyL was 0.017 ± 0.002 mSv/MBq. 18 F-DCFPyL dosimetry in nine patients was obtained using novel models for the lacrimal and salivary glands, two organs with potentially dose-limiting uptake for therapy and diagnosis which lacked pre-existing models.

Rapamycin Eye Drops Suppress Lacrimal Gland Inflammation In a Murine Model of Sjögren's Syndrome

PubMed Central

Shah, Mihir; Edman, Maria C.; Reddy Janga, Srikanth; Yarber, Frances; Meng, Zhen; Klinngam, Wannita; Bushman, Jonathan; Ma, Tao; Liu, Siyu; Louie, Stan; Mehta, Arjun; Ding, Chuanqing; MacKay, J. Andrew; Hamm-Alvarez, Sarah F.

2017-01-01

Purpose To evaluate the efficacy of topical rapamycin in treating autoimmune dacryoadenitis in a mouse model of Sjögren's syndrome. Methods We developed rapamycin in a poly(ethylene glycol)-distearoyl phosphatidylethanolamine (PEG-DSPE) micelle formulation to maintain solubility. Rapamycin or PEG-DSPE eye drops (vehicle) were administered in a well-established Sjögren's syndrome disease model, the male nonobese diabetic (NOD) mice, twice daily for 12 weeks starting at 8 weeks of age. Mouse tear fluid was collected and tear Cathepsin S, a putative tear biomarker for Sjögren's syndrome, was measured. Lacrimal glands were retrieved for histological evaluation, and quantitative real-time PCR of genes associated with Sjögren's syndrome pathogenesis. Tear secretion was measured using phenol red threads, and corneal fluorescein staining was used to assess corneal integrity. Results Lymphocytic infiltration of lacrimal glands from rapamycin-treated mice was significantly (P = 0.0001) reduced by 3.8-fold relative to vehicle-treated mice after 12 weeks of treatment. Rapamycin, but not vehicle, treatment increased tear secretion and decreased corneal fluorescein staining after 12 weeks. In rapamycin-treated mice, Cathepsin S activity was significantly reduced by 3.75-fold in tears (P < 0.0001) and 1.68-fold in lacrimal gland lysates (P = 0.003) relative to vehicle-treated mice. Rapamycin significantly altered the expression of several genes linked to Sjögren's syndrome pathogenesis, including major histocompatibility complex II, TNF-α, IFN-γ, and IL-12a, as well as Akt3, an effector of autophagy. Conclusions Our findings suggest that topical rapamycin reduces autoimmune-mediated lacrimal gland inflammation while improving ocular surface integrity and tear secretion, and thus has potential for treating Sjögren's syndrome–associated dry eye. PMID:28122086

Topical Application of Apricot Kernel Extract Improves Dry Eye Symptoms in a Unilateral Exorbital Lacrimal Gland Excision Mouse

PubMed Central

Kim, Chan-Sik; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Junghyun

2016-01-01

The purpose of this study was to investigate the therapeutic effects of topical application of apricot kernel extract (AKE) in a unilateral exorbital lacrimal gland excision mouse model of experimental dry eye. Dry eye was induced by surgical removal of the lacrimal gland. Eye drops containing 0.5 or 1 mg/mL AKE were administered twice a day from day 3 to day 7 after surgery. Tear fluid volume and corneal irregularity scores were determined. In addition, we examined the immunohistochemical expression level of Muc4. The topical administration of AKE dose-dependently improved all clinical dry eye symptoms by promoting the secretion of tear fluid and mucin. Thus, the results of this study indicate that AKE may be an efficacious topical agent for treating dry eye disease. PMID:27886047

Topical Application of Apricot Kernel Extract Improves Dry Eye Symptoms in a Unilateral Exorbital Lacrimal Gland Excision Mouse.

PubMed

Kim, Chan-Sik; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Junghyun

2016-11-23

The purpose of this study was to investigate the therapeutic effects of topical application of apricot kernel extract (AKE) in a unilateral exorbital lacrimal gland excision mouse model of experimental dry eye. Dry eye was induced by surgical removal of the lacrimal gland. Eye drops containing 0.5 or 1 mg/mL AKE were administered twice a day from day 3 to day 7 after surgery. Tear fluid volume and corneal irregularity scores were determined. In addition, we examined the immunohistochemical expression level of Muc4. The topical administration of AKE dose-dependently improved all clinical dry eye symptoms by promoting the secretion of tear fluid and mucin. Thus, the results of this study indicate that AKE may be an efficacious topical agent for treating dry eye disease.

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PubMed

Wajda, Brynn N; Mancini, Ronald; Evers, Bret; Nick Hogan, R

2018-06-23

To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

Corneal Sensitivity Following Lacrimal Gland Excision in the Rat

PubMed Central

Meng, Ian D.; Barton, Stephen T.; Mecum, Neal E.; Kurose, Masayuki

2015-01-01

Purpose. Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the present study was to assess nociceptive behaviors in an aqueous tear deficiency model of DED in the rat. Methods. Spontaneous blinking, corneal mechanical thresholds, and eye wipe behaviors elicited by hypertonic saline (5.0 M) were examined over a period of 8 weeks following the unilateral excision of either the exorbital lacrimal gland or of the exorbital and infraorbital lacrimal glands, and in sham surgery controls. The effect of topical proparacaine on spontaneous blinking and of systemic morphine (0.5–3.0 mg/kg, subcutaneous [SC]) on spontaneous blinking and eye wipe responses were also examined. Results. Lacrimal gland excision resulted in mechanical hypersensitivity and an increase in spontaneous blinking in the ipsilateral eye over an 8-week period that was more pronounced after infra- and exorbital gland excision. The time spent eye wiping was also enhanced in response to hypertonic saline (5.0 M) at both 1- and 8-week time-points, but only in infra- and exorbital gland excised animals. Morphine attenuated spontaneous blinking, and the response to hypertonic saline in dry eye animals and topical proparacaine application reduced spontaneous blinking down to control levels. Conclusions. These results indicate that aqueous tear deficiency produces hypersensitivity in the rat cornea. In addition, the increase in spontaneous blinks and their reduction by morphine and topical anesthesia indicate the presence of persistent irritation elicited by the activation of corneal nociceptors. PMID:26024120

Neurostimulation of the Lacrimal Nerve for Enhanced Tear Production

PubMed Central

Kossler, Andrea L.; Wang, Jianhua; Feuer, William; Tse, David T.

2014-01-01

Purpose To design a proof-of-concept study to assess the effect of lacrimal nerve stimulation (LNS) with an implantable pulse generator (IPG) to increase aqueous tear production. Methods Experimental animal study design of six Dutch Belted rabbits. Ultra high-resolution optical coherence tomography (UHR-OCT) quantified tear production by measuring the baseline tear volume of each rabbit’s right and left eye. A neurostimulator was implanted adjacent to the right lacrimal nerve. After two minutes of LNS (100 μs, 1.6 mAmp, 20 Hz, 5–8 volts), the tear volumes were measured with UHR-OCT. The change in tear volume was quantified and compared to the non-stimulated left eye. Three rabbits underwent chronic LNS (100 μS, 1.6 mAmp, 10 Hz, 2 volts) and their lacrimal glands were harvested for histopathologic analysis. Results UHR-OCT imaging of the right eyes tear volume showed a 441% average increase in tear production after LNS as a percent of baseline. After stimulation, right eyes had statistically significant greater increase in tear volumes than left eyes (p=0.028, Wilcoxon test). Post-stimulation right eye tear volumes were significantly greater compared to baseline (p=0.028, Wilcoxon test). Histopathologic examination of the lacrimal glands showed no discernible tissue damage from chronic neurostimulation. Additionally, there were no gross adverse effects on the general well-beings of the animals due to chronic stimulation. Conclusions Lacrimal nerve stimulation with an implantable pulse generator appears to increase aqueous tear production. Chronic LNS showed no histopathologic lacrimal gland damage. This study suggests LNS is a promising new treatment strategy to increase aqueous tear production. PMID:25126767

A novel treatment for keratitis sicca (Dry eye): Anatomical feasibility study.

PubMed

Iwanaga, Joe; Watanabe, Koichi; Kusukawa, Jingo; Fisahn, Christian; Alonso, Fernando; Oskouian, Rod J; Tubbs, R Shane

2017-09-01

Chronic dry eye (keratitis sicca) is a significant problem that in certain populations can result in corneal desiccation and the potential for blindness. Therefore, novel treatments for such disorders might decrease patient morbidity. The present study aimed to investigate a potential treatment for chronic dry eye via a cadaveric feasibility study. On 10 cadaveric sides, the parotid gland branch of the auriculotemporal nerve (ATN) was identified and anastomosed to an anterior superficial temporal branch (STb) of this same nerve. The STb was then transposed anteriorly and sutured to the lacrimal gland. The parotid branch of the ATN was easily identified on all sides. The STb of the ATN was easily identified and mobilized on all sides. This latter nerve had adequate length to be moved to the ipsilateral lacrimal gland on all sides. Rerouting parotid gland secretomotor fibers to the superficial branch of the ATN and then moving this branch to the lacrimal gland is a feasible surgical maneuver based on our cadaveric study. Clinical studies are now necessary to show utility of this procedure in patients with chronic dry eye. Clin. Anat. 30:839-843, 2017. © 2017Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Unilateral orbital lacrimal gland abscess in a horse.

PubMed

Greenberg, Shari M; Plummer, Caryn E; Brooks, Dennis E; Porter, Michael; Farina, Lisa L; Winter, Matthew D

2011-01-01

A 20-year-old Thoroughbred gelding presented for evaluation of a periorbital dorsal swelling of the left eye that had been intermittently present for 3 months. Upon ocular examination, a firm, non-painful swelling was identified under the upper eyelid in the region of the orbital lacrimal gland, and was noted to extend anteriorly from underneath the dorsal orbital rim. Ultrasonographic examination revealed a mixed echogenic mass along the dorsal orbital rim that followed the contour of the globe. CT scan showed a moderately contrast enhancing mass that was contiguous with the eyelid. Differential diagnoses included neoplasia, inflammatory lesions such as a granuloma, foreign body or abscess. Surgical exploration and excision of the mass revealed a lobular structure with a purulent center. Histopathology identified the mass as the orbital lacrimal gland with concurrent severe dacryoadenitis. Culture of the purulent center of the mass revealed beta-hemolytic Staphylococcus aureus. The patient was maintained on supportive care and antibiotic treatment based on sensitivity postoperatively. No recurrence was reported 40 months later. This paper aims to identify bacterial dacryoadenitis as a cause for unilateral periorbital swelling in the horse. Differential diagnoses for this presentation, as well as successful surgical management are discussed. To the author's knowledge, this is the first case of bacterial dacryoadenitis and subsequent abscessation of the orbital lacrimal gland in the horse. © 2011 American College of Veterinary Ophthalmologists.

Cryopreservation and hypothermic storage of lacrimal gland: towards enabling delivery of regenerative medicine therapies for treatment of dry eye syndrome.

PubMed

Massie, I; Spaniol, K; Geerling, G; Schrader, S

2017-12-01

Severe dry eye syndrome (DES) can cause painful loss of vision and may result from lacrimal gland dysfunction. Current treatments are palliative, so a causative therapy is desirable. The ability to (cryo)preserve lacrimal gland tissue or epithelial cells would simplify this. Here, lacrimal gland tissue was cryopreserved in 10% dimethylsulphoxide in liquid nitrogen, or stored at 4 °C in culture medium for up to 7 days, and compared with fresh tissue using immunohistochemistry. Cultures were initiated from fresh and stored tissue, and cells characterised in P1 for proliferation (WST-1), colony-forming efficiency (CFE) and secretory capacity (immunocytochemistry and β-hexosaminidase activity assay). Tissue stored for > 3 days at 4 °C displayed grossly altered tissue architecture when compared with fresh tissue, decreased acinus density and increased caspase-3 activity. Cryopreserved tissue showed less obvious signs of damage without caspase-3 activation. Storage at 4 °C and cryopreservation delayed epithelial outgrowth compared with that from fresh tissue initially (p  <  0.05) but, by day 9, all explants showed comparable outgrowth (~90%), except tissue stored at 4 °C for 3 or 7 days (p  <  0.05 compared with fresh tissue). Epithelial cell yields per explant were similar from fresh and stored tissue, apart from tissue stored at 4 °C for 7 days (p  <  0.01). In P1, epithelial cells from fresh and stored tissue were largely equivalent in terms of: proliferation; CFE (~21%); Rab3D, HexA and lysozyme expression; mucin production; and β-hexosaminidase activity. These data demonstrate that cryo(preservation) of lacrimal gland tissue and cells is possible, which may enable use of autologous cells in regenerative medicine approaches to treating DES. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Managing Sjögren's Syndrome and non-Sjögren Syndrome dry eye with anti-inflammatory therapy.

PubMed

Coursey, Terry G; de Paiva, Cintia S

2014-01-01

Dry eye from Sjögren's syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti-inflammatory therapies used to control this disease.

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer

PubMed Central

Ahmadzadehfar, Hojjat; Kürpig, Stefan; Eppard, Elisabeth; Kotsikopoulos, Charalambos; Liakos, Nikolaos; Bundschuh, Ralph A.; Strunk, Holger; Essler, Markus

2017-01-01

Radioligand therapy (RLT) with Lu-177-labeled PSMA-ligands is a new therapy option for prostate cancer. Biodistribution in normal tissues is of interest for therapy planning. We evaluated if the biodistribution of Ga-68-PSMA-11 is influenced by tumor load. Results In patients with high tumor load, SUVmean was reduced to 61.5% in the lacrimal glands, to 56.6% in the parotid glands, to 63.7% in the submandibular glands, to 61.3% in the sublingual glands and to 55.4% in the kidneys (p < 0.001). Further significant differences were observed for brain, mediastinum, liver, spleen and muscle. Total tracer retention was higher in patients with high tumor load (p < 0.05). SUV in lacrimal, salivary glands and kidneys correlated negatively with PSA. Materials and Methods 135 patients were retrospectively evaluated. SUV was measured in the lacrimal and salivary glands, brain, heart, liver, spleen, kidneys, muscle and bone. SUV was correlated with visual tumor load, total tracer retention and PSA. Conclusions Patients with high tumor load show a significant reduction of tracer uptake in dose-limiting organs. As similar effects might occur when performing RLT using Lu-177-labeled PSMA-ligands, individual adaptations of therapy protocols based on diagnostic PSMA PET imaging before therapy might help to further increase efficacy and safety of RLT. PMID:28903405

Lacrimal fossa lesions: a review of 146 cases in Egypt

PubMed Central

Eldesouky, Mohammed A; Elbakary, Molham A; Sabik, Saly; Shareef, Mohamed M

2014-01-01

Purpose The incidence and clinical and imaging criteria of different pathological forms of lacrimal fossa lesions in the Delta region of Egypt were studied. Methods A retrospective study of patients with lacrimal fossa lesions for the past 10 years was conducted. A total of 146 cases were identified. Their medical records were reviewed for clinical and imaging data (computed tomography scan, magnetic resonance imaging scan, or both). A definitive diagnosis based on pathological examination of biopsies was also reviewed. Results Among the patients reviewed, 43.15% had inflammatory lacrimal gland lesions, 26.71% had lymphoproliferative lesions, and 21.92% had epithelial lesions; 8.22% had rare lesions (5.48% were dacryops and 2.74% had hemangioma). The study included 71.92% benign lesions and 28.08% malignant lesions, which were distributed between 19.18% malignant lymphoma and 8.9% malignant epithelial tumors. According to the pathological origin of the lesions, they may be classified into 78.08% nonepithelial lesions and 21.92% epithelial lesions (16.44% epithelial tumors, and 5.48% dermoid cysts). Conclusion Lacrimal fossa lesions show a wide pathological range. Inflammatory lesions are most frequent, followed by lymphoproliferative and epithelial lesions. Analysis of clinical and radiological criteria is helpful in the differential diagnosis of lacrimal gland lesions. PMID:25210428

Adenoid cystic carcinoma of the lacrimal gland.

PubMed

Sanders, Jason C; Mendenhall, William M; Werning, John W

2016-01-01

This is a retrospective analysis of the 50-year University of Florida experience treating adenoid cystic carcinoma of the lacrimal gland with radiation therapy. Between 1965 and 2015, 8 patients with adenoid cystic carcinoma of the lacrimal gland received radiation therapy with curative intent. Four patients received postoperative radiation therapy and 4 received definitive radiation therapy alone. The median follow-up was 3.3 years (range, 0.3 to 11.2 years). All 4 patients who received postoperative radiation therapy received 74.4 Gy. The 4 patients who received radiation therapy alone received a median dose of 72.3 Gy (range, 70.0 to 74.4 Gy). The overall survival rates at 5 and 10 years were 25% and 13%, respectively. The cause-specific survival rates at 5 and 10 years were 29% and 14%, respectively. The local control and freedom from metastases rates at 5 and 10 years were both 43%. Local recurrences occurred in 50% of patients, and distant metastatic disease occurred in 38% of patients. No patients experienced acute complications of treatment that warranted a treatment break. Two patients experienced bone exposure as late complications of treatment. The results of this study illustrate the propensity for adenoid cystic carcinoma of the lacrimal gland to recur both locally and with distant metastases despite aggressive local treatment measures. This study also demonstrates the relatively poor outcomes for individuals with this type of tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiologic distribution of PSMA-ligand in salivary glands and seromucous glands of the head and neck on PET/CT.

PubMed

Klein Nulent, Thomas J W; Valstar, Matthijs H; de Keizer, Bart; Willems, Stefan M; Smit, Laura A; Al-Mamgani, Abrahim; Smeele, Ludwig E; van Es, Robert J J; de Bree, Remco; Vogel, Wouter V

2018-05-01

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is used for detection and (re)staging of prostate cancer. However, healthy salivary, seromucous, and lacrimal glands also have high PSMA-ligand uptake. This study aimed to describe physiologic PSMA-ligand uptake distribution characteristics in the head and neck to aid in PSMA PET/CT interpretation and to identify possible new clinical applications for PSMA-ligand imaging. Thirty consecutive patients who underwent PSMA PET/CT for prostate cancer were evaluated. Tracer maximum standardized uptake values (SUV max ) in the salivary, seromucous, and lacrimal glands were determined visually and quantitatively. Overall and intraindividual variations were reported. All gland locations had increased tracer uptake. The mean SUV max  ± standard deviation varied: parotid 12.3 ± 3.9; submandibular 11.7 ± 3.5; sublingual 4.5 ± 1.9; soft palate 2.4 ± 0.5; pharyngeal wall 4.3 ± 1.3; nasal mucosa 3.4 ± 0.9; supraglottic larynx 2.7 ± 0.7; and lacrimal 6.2 ± 2.2. The parotid had the largest overall variation in SUV max (5.2-22.9), and the sublingual glands had the largest mean intraindividual difference (18.1%). Major and minor salivary and seromucous glands consistently have high PSMA-ligand uptake. Minor gland locations can be selectively visualized by this technique for the first time. This provides potential new applications such as quantification of present salivary gland tissues and individualization of radiotherapy for head and neck cancer or lutetium-177-PSMA radionuclide treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Managing Sjögren’s Syndrome and non-Sjögren Syndrome dry eye with anti-inflammatory therapy

PubMed Central

Coursey, Terry G; de Paiva, Cintia S

2014-01-01

Dry eye from Sjögren’s syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti–inflammatory therapies used to control this disease. PMID:25120351

Orbital adenocarcinoma of lacrimal gland origin in a dog.

PubMed

Wang, F I; Ting, C T; Liu, Y S

2001-03-01

A 13-year-old intact female mixed-breed dog was presented for a progressive enlargement of the right eye, which had been treated previously for conjunctivitis. A round, firm mass, approximately 4 cm in diameter, was protruding from the superotemporal aspect of the right orbit, displacing the eyeball anteriorly and ventromedially. The mass was encapsulated, distinct from the eyeball, and not associated with the eyelids. On cut surface, there was a pale multilobulated periphery, with a dark red, soft, and depressed core. Histologically, tumor cells formed cords and tubules, which were stained with mouse anti-human cytokeratin antibody AE1/AE3. Residual glands were serous, and the majority of tumor cells were negative for mucin. The supraorbital location, encapsulation, and residual serous glands suggest that this mass was a low-grade adenocarcinoma of the lacrimal gland.

[Lacrimal gland-associated mucins. Age related production and their role in the pathophysiology of dry eye].

PubMed

Schäfer, G; Hoffmann, W; Berry, M; Paulsen, F

2005-02-01

The secretory cells of the human lacrimal gland show a PAS-positive reaction in cytochemical staining procedures, suggesting the production of mucous substances. Recently, these substances were differentiated according to modern molecular classifications. Expression studies detected mRNA for MUC1, MUC4, MUC5AC, MUC5B, MUC6, and MUC7, whereas MUC2 transcripts were absent in all samples investigated. Immunohistochemistry revealed membrane-bound MUC1 at the apical surface of acinar cells, MUC5AC associated with goblet cells of excretory ducts, MUC5B and MUC7 in the cytoplasm of acinar cells, and MUC7 also in epithelial cells of excretory ducts. MUC2 (RT-PCR negative) and MUC6 (RT-PCR positive) were not detectable by immunohistochemistry. MUC4 mRNA was present in all samples from patients treated for dry eye but only in 6 of 30 glands from individuals who did not receive treatment with artificial tears. Dot-blot analyses clearly revealed increased amounts of MUC4, MUC5AC and MUC5B in the glands of elderly women who received treatment for dry eye as compared to the remaining samples. These results confirm that the human lacrimal gland synthesizes a spectrum of mucins, some of which might be involved in the pathophysiology of dry eye syndrome.

Effects of silk fibroin in murine dry eye

NASA Astrophysics Data System (ADS)

Kim, Chae Eun; Lee, Ji Hyun; Yeon, Yeung Kyu; Park, Chan Hum; Yang, Jaewook

2017-03-01

The study aimed to investigate the effects of silk fibroin in a mouse model of dry eye. The experimental dry eye mouse model was developed using more than twelve-weeks-old NOD.B10.H2b mice exposing them to 30-40% ambient humidity and injecting them with scopolamine hydrobromide for 10 days. Tear production and corneal irregularity score were measured by the instillation of phosphate buffered saline or silk fibroin. Corneal detachment and conjunctival goblet cell density were observed by hematoxylin and eosin or periodic acid Schiff staining in the cornea or conjunctiva. The expression of inflammatory markers was detected by immunohistochemistry in the lacrimal gland. The silk group tear production was increased, and corneal smoothness was improved. The corneal epithelial cells and conjunctival goblet cells were recovered in the silk groups. The expression of inflammatory factors was inhibited in the lacrimal gland of the silk group. These results show that silk fibroin improved the cornea, conjunctiva, and lacrimal gland in the mouse model of dry eye. These findings suggest that silk fibroin has anti-inflammatory effects in the experimental models of dry eye.

Signaling Pathways of Purinergic Receptors and Their Interactions with Cholinergic and Adrenergic Pathways in the Lacrimal Gland

PubMed Central

Hodges, Robin R.

2016-01-01

Abstract Purpose: Purinergic receptors play a key role in the function of the lacrimal gland (LG) as P1 purinergic receptors A1, A2A, and A2B, P2X1–7 receptors, and many of the P2Y receptors are expressed. Methods: This review examines the current knowledge of purinergic receptors in the LG as well as the signaling pathways activated by these receptors. Results: These receptors are expressed on the acinar, ductal, and myoepithelial cells. Considerable crosstalk exists between the pathways activated by P2X7 receptors with those activated by M3 muscarinic or α1D adrenergic receptors. The mechanism of the crosstalk between P2X7 and M3 muscarinic receptors differs from that of the crosstalk between P2X7 and α1D adrenergic receptors. Conclusions: Understanding purinergic receptors and how they modulate protein secretion could play a key role in normal and pathological responses of the LG. PMID:27463365

Oral administration of royal jelly restores tear secretion capacity in rat blink-suppressed dry eye model by modulating lacrimal gland function.

PubMed

Imada, Toshihiro; Nakamura, Shigeru; Kitamura, Naoki; Shibuya, Izumi; Tsubota, Kazuo

2014-01-01

Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG.

Lacritin and other new proteins of the lacrimal functional unit.

PubMed

McKown, Robert L; Wang, Ningning; Raab, Ronald W; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B; Laurie, Gordon W

2009-05-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as 'an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them'. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over 200 new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin's low nanomolar mitogenic activity. The lacritin-binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction.

Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland.

PubMed

Le Tourneau, Christophe; Razak, Albiruni R A; Levy, Christine; Calugaru, Valentin; Galatoire, Olivier; Dendale, Rémi; Desjardins, Laurence; Gan, Hui K

2011-11-01

Adenoid cystic carcinoma (ACC) is the most common malignant epithelial cancer of the lacrimal gland. Despite a slow rate of growth, ACCs are ultimately associated with poor clinical outcome. Given the rarity of this disease, most recommendations regarding therapy are guided by expert opinion and retrospective data rather than level 1 evidence. Surgery and postoperative radiation therapy are commonly used as initial local treatment. In patients at high risk of recurrence, concomitant platinum-based chemotherapy may be added to postoperative radiotherapy in an attempt to enhance radio-sensitivity. While encouraging responses have been reported with intra-arterial neoadjuvant chemotherapy, this strategy is associated with substantial toxicity and should be considered investigational. For patients with metastatic disease not amenable to surgery or radiotherapy, chemotherapy may have a role based on its modest efficacy in non-lacrimal ACC. Similarly, molecular targeted agents may have a role, although the agents tested to date in non-lacrimal ACC have been disappointing. A better understanding of the biology of ACC will be crucial to the future success of developing targeted agents for this disease.

Primary lymphocytic lymphoma of lacrimal gland.

PubMed

Romero-Caballero, M D; Lozano-García, I; Gómez-Molina, C; Gil-Liñán, A I; Arcas, I

2017-02-01

We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Management of the ocular surface and tear film before, during, and after laser in situ keratomileusis.

PubMed

Albietz, Julie M; Lenton, Lee M

2004-01-01

To identify evidence-based, best practice strategies for managing the ocular surface and tear film before, during, and after laser in situ keratomileusis (LASIK). After a comprehensive review of relevant published literature, evidence-based recommendations for best practice management strategies are presented. Symptoms of ocular irritation and signs of dysfunction of the integrated lacrimal gland/ocular surface functional gland unit are common before and after LASIK. The status of the ocular surface and tear film before LASIK can impact surgical outcomes in terms of potential complications during and after surgery, refractive outcome, optical quality, patient satisfaction, and the severity and duration of dry eye after LASIK. Before LASIK, the health of the ocular surface should be optimized and patients selected appropriately. Dry eye before surgery and female gender are risk factors for developing chronic dry eye after LASIK. Management of the ocular surface during LASIK can minimize ocular surface damage and the risk of adverse outcomes. Long-term management of the tear film and ocular surface after LASIK can reduce the severity and duration of dry eye symptoms and signs. Strategies to manage the integrated ocular surface/lacrimal gland functional unit before, during, and after LASIK can optimize outcomes. As problems with the ocular surface and tear film are relatively common, attention should focus on the use and improvement of evidence-based management strategies.

Diabetes-associated dry eye syndrome in a new humanized transgenic model of type 1 diabetes.

PubMed

Imam, Shahnawaz; Elagin, Raya B; Jaume, Juan Carlos

2013-01-01

Patients with Type 1 Diabetes (T1D) are at high risk of developing lacrimal gland dysfunction. We have developed a new model of human T1D using double-transgenic mice carrying HLA-DQ8 diabetes-susceptibility haplotype instead of mouse MHC-class II and expressing the human beta cell autoantigen Glutamic Acid Decarboxylase in pancreatic beta cells. We report here the development of dry eye syndrome (DES) after diabetes induction in our humanized transgenic model. Double-transgenic mice were immunized with DNA encoding human GAD65, either naked or in adenoviral vectors, to induce T1D. Mice monitored for development of diabetes developed lacrimal gland dysfunction. Animals developed lacrimal gland disease (classically associated with diabetes in Non Obese Diabetic [NOD] mice and with T1D in humans) as they developed glucose intolerance and diabetes. Animals manifested obvious clinical signs of dry eye syndrome (DES), from corneal erosions to severe keratitis. Histological studies of peri-bulbar areas revealed lymphocytic infiltration of glandular structures. Indeed, infiltrative lesions were observed in lacrimal/Harderian glands within weeks following development of glucose intolerance. Lesions ranged from focal lymphocytic infiltration to complete acinar destruction. We observed a correlation between the severity of the pancreatic infiltration and the severity of the ocular disease. Our results demonstrate development of DES in association with antigen-specific insulitis and diabetes following immunization with clinically relevant human autoantigen concomitantly expressed in pancreatic beta cells of diabetes-susceptible mice. As in the NOD mouse model and as in human T1D, our animals developed diabetes-associated DES. This specific finding stresses the relevance of our model for studying these human diseases. We believe our model will facilitate studies to prevent/treat diabetes-associated DES as well as human diabetes.

Transfrontal orbitotomy in the dog: an adaptable three-step approach to the orbit.

PubMed

Håkansson, Nils Wallin; Håkansson, Berit Wallin

2010-11-01

To describe an adaptable and extensive method for orbitotomy in the dog. An adaptable three-step technique for orbitotomy was developed and applied in nine consecutive cases. The steps are zygomatic arch resection laterally, temporalis muscle elevation medially and zygomatic process osteotomy anteriorly-dorsally. The entire orbit is accessed with excellent exposure and room for surgical manipulation. Facial nerve, lacrimal nerve and lacrimal gland function are preserved. The procedure can easily be converted into an orbital exenteration. Exposure of the orbit was excellent in all cases and anatomically correct closure was achieved. Signs of postoperative discomfort were limited, with moderate, reversible swelling in two cases and mild in seven. Wound infection or emphysema did not occur, nor did any other complication attributable to the operative procedure. Blinking ability and lacrimal function were preserved over follow-up times ranging from 1 to 4 years. Transfrontal orbitotomy in the dog offers excellent exposure and room for manipulation. Anatomically correct closure is easily accomplished, postoperative discomfort is limited and complications are mild and temporary. © 2010 American College of Veterinary Ophthalmologists.

Microporous Poly(L-Lactic Acid) Membranes Fabricated by Polyethylene Glycol Solvent-Cast/Particulate Leaching Technique

PubMed Central

Selvam, Shivaram; Chang, Wenji V.; Nakamura, Tamako; Samant, Deedar M.; Thomas, Padmaja B.; Trousdale, Melvin D.; Mircheff, Austin K.; Schechter, Joel E.

2009-01-01

With the eventual goal of developing a tissue-engineered tear secretory system, we found that primary lacrimal gland acinar cells grown on solid poly(L-lactic acid) (PLLA) supports expressed the best histiotypic morphology. However, to be able to perform vectorial transport functions, epithelia must be supported by a permeable substratum. In the present study, we describe the use of a solvent-cast/particulate leaching technique to fabricate microporous PLLA membranes (mpPLLAm) from PLLA/polyethylene glycol blends. Scanning electron microscopy revealed pores on both the air-cured (∼4 μm) and glass-cured sides (<2 μm) of the mpPLLAm. Diffusion studies were performed with mpPLLAm fabricated from 57.1% PLLA/42.9% polyethylene glycol blends to confirm the presence of channelized pores. The data reveal that glucose, L-tryptophan, and dextran (a high molecular weight glucose polymer) readily permeate mpPLLAm. Diffusion of the immunoglobulin G through the mpPLLAm decreased with time, suggesting the possible adsorption and occlusion of the pores. Cells cultured on the mpPLLAm (57.1/42.9 wt%) grew to subconfluent monolayers but retained histiotypic morphological and physiological characteristics of lacrimal acinar cells in vivo. Our results suggest that mpPLLAm fabricated using this technique may be useful as a scaffold for a bioartificial lacrimal gland device. PMID:19260769

Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye.

PubMed

Zheng, Wenjing; Ma, Mingming; Du, Ergang; Zhang, Zhengwei; Jiang, Kelimu; Gu, Qing; Ke, Bilian

2015-11-01

The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate‑buffered saline (PBS; PBS control group) or 25 µg/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain‑optical coherence tomography. Tear membrane break‑up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription‑quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultrastructure7 days after treatment. The percentages of apoptotic corneal‑ and Cj‑ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10 significantly induced the mRNA expression of Muc1 in the corneal epithelial cells, compared with the normal control group, and induced higher mRNA expression levels of Muc1 in the Cj‑ECs, compared with the PBS control group. In the present study, the rabbit dry eye model was successfully established 3 days after lacrimal gland Con A injection. FGF10 eye drops increased TMH and TMA, promoted corneal epithelial healing, reduced apoptosis of the corneal- and Cj-ECs and led to increased expression of Muc1.

Morphology and function of lacrimal gland acinar cells in primary culture.

PubMed

Hann, L E; Tatro, J B; Sullivan, D A

1989-01-01

The objectives of the current investigation were fourfold: (1) to establish an effective procedure for the isolation of acinar cells from the rat lacrimal gland; (2) to evaluate the functional capacity of freshly isolated cells; (3) to determine defined culture conditions which permit maintenance of viable, differentiated cells, as well as secretory component (SC) production, during long-term culture; and (4) to characterize the morphological features of cultured cells. Acinar cells were isolated by serial incubation of gland fragments in chelating and enzymatic solutions, followed by centrifugation through a Ficoll gradient. The yield of viable cells/gland appeared to be age-dependent: cell recovery was inversely proportional to the age of the animals. Immunofluorescence analysis of freshly isolated cells showed the presence of SC, the IgA antibody receptor, within isolated cells. In addition, experiments with a labeled analog (Nle4-D-Phe7-alpha MSH) of alpha-melanocyte-stimulating hormone (alpha-MSH) demonstrated specific binding sites on freshly isolated cells; alpha-MSH is a known modulator of acinar protein secretion. Maximum binding of the alpha-MSH analog occurred within 30 min, was dependent upon cell density and was reduced by coincubation with unlabeled alpha-MSH. To determine the culture requirements of acinar cells, cells were cultured on a variety of substrates (plastic or modified plastic [Primaria], coated with or without extracellular matrix [Matrigel]) in the presence or absence of various supplements and/or fetal calf serum (FCS) for 0.7 to 3.5 weeks. Cell attachment, function and long-term viability required an extracellular matrix. Moreover, in long term cultures (25 days), acinar cell attachment was enhanced by the inclusion of supplements to media containing 10% FCS. Replacement of serum with fibroblast growth factor, high-density lipoprotein and an increased concentration of epidermal growth factor resulted in a distinct "cobblestone" morphology characteristic of epithelial cell cultures. Electron microscopic analysis of cells cultured in supplemented serum-free media demonstrated extensive rough endoplasmic reticulum and Golgi, intermediate filaments and numerous secretory granules, as well as tight junctions and desmosomes. In addition to cell maintenance and attachment, acinar cell synthesis and/or secretion of SC was positively influenced by inclusion of supplements in the media. In summary, we have isolated lacrimal gland acinar cells, which express receptors for IgA antibodies and alpha-MSH. In addition, we have defined culture conditions which permit the long-term maintenance of SC-secreting acinar cells.

Effects of nicergoline on corneal epithelial wound healing in rat eyes.

PubMed

Kim, Su-Young; Choi, Jun-Sub; Joo, Choun-Ki

2009-02-01

To investigate the effect of nicergoline on corneal epithelial wound healing in rats. One hundred Sprague-Dawley male rats were divided into two groups, the control group and the nicergoline-treated group, for 2 weeks. Corneal wound healing was evaluated by fluorescein staining after epithelial debridement. Nerve growth factor (NGF) protein and NGF mRNA were measured in rat corneas by ELISA and RT-PCR. NGF concentration of lacrimal gland was also evaluated by means of ELISA. Immunofluorescent staining was performed in rat corneas. The corneal wound healing rate was increased in nicergoline-treated rats compared with control rats after debridement. Twenty-four hours after epithelial debridement, corneal NGF protein and NGF mRNA levels were higher in the nicergoline-treated group than in the control group. Immunofluorescent staining showed that NGF staining was stronger in nicergoline-treated corneas than in control corneas 24 hours after epithelial debridement. In addition, NGF concentrations in lacrimal glands of the nicergoline-treated group were significantly higher than in the control group 24 hours after epithelial debridement. Nicergoline accelerated wound healing in rat corneas. The promoting effect of nicergoline in corneal wound healing is likely to be related to increased NGF in corneas and lacrimal glands.

The use of botulinum toxin A in the treatment of functional epiphora.

PubMed

Whittaker, Karl W; Matthews, Bethan N; Fitt, Alan W; Sandramouli, S

2003-09-01

The purpose of this study was to investigate the hitherto undescribed effects of botulinum toxin A injected into the lacrimal gland in patients with functional epiphora. A prospective non-comparative interventional case series study was designed to include patients with functional epiphora who presented to the Oculoplastic unit at the Wolverhampton and Midland Counties Eye Infirmary. Botulinum toxin A (2.5-5 units) was injected into the palpebral lobe of the lacrimal gland on the worst affected side via a transconjunctival approach under topical anaesthesia. Patients underwent a Schirmer test and provided a subjective evaluation of their epiphora symptoms, indoors and outdoors, at baseline and at 1, 4 and 13 weeks after injection. The mean score for symptoms indoors and outdoors was calculated. Fourteen patients agreed to take part in the study. Subjective epiphora scores improved in 8 out of the 11 patients (72.7%) who completed 13 weeks of follow-up. Schirmer test results showed objective reduction in tearing from baseline but did not strongly correlate with the subjective epiphora scores. Transient mild ptosis and diplopia were experienced by two patients. The results from this small pilot study are encouraging, although larger, controlled trials are needed to assess the optimal dose of BTX-A, its long-term efficacy and safety, and the role of multiple injections.

Microarray analysis of the rat lacrimal gland following the loss of parasympathetic control of secretion

PubMed Central

Nguyen, Doan H.; Toshida, Hiroshi; Schurr, Jill; Beuerman, Roger W.

2010-01-01

Previous studies showed that loss of muscarinic parasympathetic input to the lacrimal gland (LG) leads to a dramatic reduction in tear secretion and profound changes to LG structure. In this study, we used DNA microarrays to examine the regulation of the gene expression of the genes for secretory function and organization of the LG. Long-Evans rats anesthetized with a mixture of ketamine/xylazine (80:10 mg/kg) underwent unilateral sectioning of the greater superficial petrosal nerve, the input to the pterygopalatine ganglion. After 7 days, tear secretion was measured, the animals were killed, and structural changes in the LG were examined by light microscopy. Total RNA from control and experimental LGs (n = 5) was used for DNA microarray analysis employing the U34A GeneChip. Three statistical algorithms (detection, change call, and signal log ratio) were used to determine differential gene expression using the Microarray Suite (5.0) and Data Mining Tools (3.0). Tear secretion was significantly reduced and corneal ulcers developed in all experimental eyes. Light microscopy showed breakdown of the acinar structure of the LG. DNA microarray analysis showed downregulation of genes associated with the endoplasmic reticulum and Golgi, including genes involved in protein folding and processing. Conversely, transcripts for cytoskeleton and extracellular matrix components, inflammation, and apoptosis were upregulated. The number of significantly upregulated genes (116) was substantially greater than the number of downregulated genes (49). Removal of the main secretory input to the rat LG resulted in clinical symptoms associated with severe dry eye. Components of the secretory pathway were negatively affected, and the increase in cell proliferation and inflammation may lead to loss of organization in the parasympathectomized lacrimal gland. PMID:15084711

Evaluation of Accessory Lacrimal Gland in Muller's Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease.

PubMed

Ali, Marwan; Shah, Dhara; Pasha, Zeeshan; Jassim, Sarmad H; Jassim Jaboori, Assraa; Setabutr, Pete; Aakalu, Vinay K

2017-04-01

The accessory lacrimal glands (ALGs) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential, and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics. ALG tissues obtained from Muller's muscle conjunctival resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers. Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2, and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES. Thus, we report for the first time that human ALG tissues contain precursor marker-positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES, and isolate candidate precursor cells from ALG tissue.

Cervical lymph node metastasis in adenoid cystic carcinoma of the sinonasal tract, nasopharynx, lacrimal glands and external auditory canal: a collective international review.

PubMed

2016-12-01

To review reports of adenoid cystic carcinomas arising in the head and neck area outside of the major salivary glands, in order to enhance the care of patients with these unusual neoplasms. An international team of head and neck surgeons, pathologists, oncologists and radiation oncologists was assembled to explore the published experience and their own working experience of the diagnosis and treatment of adenoid cystic carcinomas arising in the vicinity of the sinonasal tract, nasopharynx, lacrimal glands and external auditory canal. The behaviour of adenoid cystic carcinoma arising in head and neck sites exclusive of the major salivary glands parallels that of tumours with a similar histology arising in the major salivary glands - these are relentless, progressive tumours, associated with high rates of mortality. Of 774 patients reviewed, at least 41 (5.3 per cent) developed documented regional node metastases. The relatively low overall incidence of nodal metastases in adenoid cystic carcinomas arising in the head and neck region outside of the major salivary glands suggests that routine elective regional lymph node dissection might not be indicated in most patients with these tumours.

Cervical lymph node metastasis in adenoid cystic carcinoma of the sinonasal tract, nasopharynx, lacrimal glands and external auditory canal: a collective international review

PubMed Central

2017-01-01

Objective To review reports of adenoid cystic carcinomas arising in the head and neck area outside of the major salivary glands, in order to enhance the care of patients with these unusual neoplasms. Methods An international team of head and neck surgeons, pathologists, oncologists and radiation oncologists was assembled to explore the published experience and their own working experience of the diagnosis and treatment of adenoid cystic carcinomas arising in the vicinity of the sinonasal tract, nasopharynx, lacrimal glands and external auditory canal. Results The behaviour of adenoid cystic carcinoma arising in head and neck sites exclusive of the major salivary glands parallels that of tumours with a similar histology arising in the major salivary glands – these are relentless, progressive tumours, associated with high rates of mortality. Of 774 patients reviewed, at least 41 (5.3 per cent) developed documented regional node metastases. Conclusion The relatively low overall incidence of nodal metastases in adenoid cystic carcinomas arising in the head and neck region outside of the major salivary glands suggests that routine elective regional lymph node dissection might not be indicated in most patients with these tumours. PMID:27839526

Light microscopic detection of sugar residues in glycoconjugates of salivary glands and the pancreas with lectin-horseradish peroxidase conjugates. I. Mouse.

PubMed

Schulte, B A; Spicer, S S

1983-12-01

Mouse salivary glands and pancreases were stained with a battery of ten horseradish peroxidase-conjugated lectins. Lectin staining revealed striking differences in the structure of oligosaccharides of stored intracellular secretory glycoproteins and glycoconjugates associated with the surface of epithelial cells lining excretory ducts. The percentage of acinar cells containing terminal alpha-N-acetylgalactosamine residues varied greatly in submandibular glands of 30 male mice, but all submandibular acinar cells contained oligosaccharides with terminal sialic acid and penultimate beta-galactose residues. The last named dimer was abundant in secretory glycoprotein of all mucous acinar cells in murine sublingual glands and an additional 20-50% of these cells in all glands contained terminal N-acetylglucosamine residues. In contrast, terminal alpha-N-acetylgalactosamine was abundant in sublingual serous demilune secretions. Serous acinar cells in the exorbital lacrimal gland, posterior lingual gland, parotid gland and pancreas exhibited a staining pattern unique to each organ. In contrast, the apical cytoplasm and surface of striated duct epithelial cells in the submandibular, sublingual, parotid and exorbital lacrimal gland stained similarly. A comparison of staining with conjugated lectins reported biochemically to have very similar carbohydrate binding specificity has revealed some remarkable differences in their reactivity, suggesting different binding specificity for the same terminal sugars having different glycosidic linkages or with different penultimate sugar residues.

[Bilateral "crocodile tears syndrome" associated with Melkersson-Rosenthal syndrome--case report].

PubMed

Owecki, Michał K; Kapelusiak-Pielok, Magdalena; Kowal, Piotr; Kozubski, Wojciech

2006-01-01

We present a rare case of bilateral crocodile tears syndrome (CTS) in the course of Melkersson-Rosenthal syndrome. Melkersson-Rosenthal syndrome is characterised by a triad of recurrent orofacial swelling, relapsing facial paralysis, and fissured tongue. The classic triad is infrequent and oligosymptomatic variants are seen more frequently. CTS is a rare complication of facial nerve paralysis characterised by inappropriate lacrimation on the side of the palsy in response to salivary stimuli. It results from aberrant reinnervation of the lacrimal gland by salivary parasympathetic fibres. The therapeutic approach for an acute bout of Melkersson-Rosenthal syndrome consists mainly of steroid administration. CTS management is composed of anticholinergic drugs and surgical procedures. Botulin toxin injection into the lacrimal gland is the most modern therapeutic option. In the case presented CTS developed in a 50-year-old man after 5 incidents of facial palsy due to Melkersson-Rosenthal syndrome. The case deserves attention due to the rarity of the observed symptoms and signs.

Recognition of distinctive patterns of gallium-67 distribution in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sulavik, S.B.; Spencer, R.P.; Weed, D.A.

1990-12-01

Assessment of gallium-67 ({sup 67}Ga) uptake in the salivary and lacrimal glands and intrathoracic lymph nodes was made in 605 consecutive patients including 65 with sarcoidosis. A distinctive intrathoracic lymph node {sup 67}Ga uptake pattern, resembling the Greek letter lambda, was observed only in sarcoidosis (72%). Symmetrical lacrimal gland and parotid gland {sup 67}Ga uptake (panda appearance) was noted in 79% of sarcoidosis patients. A simultaneous lambda and panda pattern (62%) or a panda appearance with radiographic bilateral, symmetrical, hilar lymphadenopathy (6%) was present only in sarcoidosis patients. The presence of either of these patterns was particularly prevalent in roentgenmore » Stages I (80%) or II (74%). We conclude that simultaneous (a) lambda and panda images, or (b) a panda image with bilateral symmetrical hilar lymphadenopathy on chest X-ray represent distinctive patterns which are highly specific for sarcoidosis, and may obviate the need for invasive diagnostic procedures.« less

Lacritin and Other New Proteins of the Lacrimal Functional Unit

PubMed Central

McKown, Robert L.; Wang, Ningning; Raab, Ronald W.; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B.; Laurie, Gordon W.

2009-01-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as ‘an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them’. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over two hundred new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin’s low nanomolar mitogenic activity. The lacritin binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction. PMID:18840430

Compensatory increases in tear volume and mucin levels associated with meibomian gland dysfunction caused by stearoyl-CoA desaturase-1 deficiency.

PubMed

Inaba, Takaaki; Tanaka, Yasuhisa; Tamaki, Shusaku; Ito, Tomotaka; Ntambi, James M; Tsubota, Kazuo

2018-02-20

The stearoyl-CoA desaturase (SCD) family of enzymes catalyzes monounsaturated fatty acid synthesis by inserting a cis double bond at the Δ9 position of saturated fatty acids. Disruption of these enzymes has been reported to induce a severe dry skin phenotype. Since lipid abnormalities in the meibomian glands have been associated with dry eye, we analyzed selected eye tissues contributing to tear volume and composition in genetically SCD-1-deficient mice (SCD-1 KO), including the lacrimal glands and conjunctiva. Previous histopathological analysis had revealed atrophy and loss of meibomian glands; taken together with the increased goblet cell and MUC5AC expression in the conjunctiva reported here, these findings suggest that the tear volume and mucin levels secreted are enhanced in the absence of lipid secretion as a compensatory mechanism. The expression of lipid metabolism genes in lacrimal glands was decreased in SCD1 KO mice. Thus, these results provide new pathophysiological mechanisms to pursue with regard to meibomian gland dysfunction. In addition, lack of SCD-1 causes a compensatory increase in the tear volume and mucin levels associated with changes in expression of lipid metabolism genes. These results may be useful as a new concept for dry eye treatment strategies.

Staging and follow-up of lacrimal gland carcinomas by 18F-FDG PET/CT imaging.

PubMed

Tafti, Bashir Akhavan; Shaba, Wisam; Li, Yuxin; Yevdayev, Ella; Berenji, Gholam Reza

2012-10-01

A 74-year-old man with right eye proptosis, diplopia, and orbital discomfort for 3 to 4 months underwent biopsy, the specimen of which showed transitional cell carcinoma of the lacrimal gland. 18F-FDG PET/CT was also performed for staging purposes. Six months after orbital exenteration, a follow-up CT scan demonstrated soft tissue thickening along the nasal bridge but could not differentiate between postsurgical changes and cancer recurrence. A concurrent PET/CT scan did not show any evidence of abnormal metabolic activity, further emphasizing the higher accuracy of PET/CT in staging and restaging of head and neck cancers. An annual follow-up scan was still negative for active disease.

Lacrimal neuralgia: so far, a missing cranial neuralgia.

PubMed

Pareja, Juan A; Cuadrado, María-Luz

2013-10-01

The lacrimal nerve supplies the lacrimal gland, the lateral upper eyelid, and a small cutaneous area adjacent to the external CANTHUS . First division trigeminal neuralgia, supraorbital/supratrochlear neuralgia, and infraorbital neuralgia have been acknowledged as neuralgic causes of pain in the forehead and periorbit. However, the lacrimal nerve has never been identified as a source of facial pain. Here we report two cases of lacrimal neuralgia. A 66-year-old woman had continuous pain in the lateral aspect of her left superior eyelid and an adjacent area of the temple since age 64. A 33-year-old woman suffered from continuous pain in a small area next to the lateral CANTHUS of her left eye since age 25. In both patients the superoexternal edge of the orbit was tender. In addition, sensory dysfunction could be demonstrated within the painful area. Anaesthetic blockades of the lacrimal nerve with lidocaine 2% resulted in complete but short-lasting relief. Pregabalin provided a complete response in the first patient. The second patient was refractory to various oral and topical drugs and different radiofrequency procedures, but she eventually obtained partial relief with pregabalin. Lacrimal neuralgia should be considered among the neuralgic causes of orbital and periorbital pain.

Evaluation of Accessory Lacrimal Gland in Muller’s Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease

PubMed Central

Ali, Marwan; Shah, Dhara; Pasha, Zeeshan; Jassim, Sarmad H.; Jaboori, Assraa Jassim; Setabutr, Pete; Aakalu, Vinay K.

2017-01-01

Purpose The accessory lacrimal glands (ALG) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics. Materials and Methods ALG tissues obtained from Muller’s Muscle Conjunctival Resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers. Results Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2 and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES. Conclusions Thus, we report for the first time that human ALG tissues contain precursor marker positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES and isolate candidate precursor cells from ALG tissue. PMID:27612554

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Autoimmune Granulomatous Inflammation of Lacrimal Glands and Axonal Neuritis Following Treatment With Ipilimumab and Radiation Therapy.

PubMed

Ileana Dumbrava, Ecaterina; Smith, Veronica; Alfattal, Rasha; El-Naggar, Adel K; Penas-Prado, Marta; Tsimberidou, Apostolia M

2018-05-21

Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response. The use of immune checkpoint inhibitors exhibit an unique toxicity profile, the immune-related adverse events (irAEs). The most notable immune reactions are noted in skin (rash), gastrointestinal track (colitis, hepatitis, pancreatitis), lung (pneumonitis), heart (myocarditis), and endocrine system (thyroiditis, hypophysitis). We present a patient with metastatic adenoid cystic carcinoma of the left submandibular gland with granulomatous inflammation of the lacrimal glands and axonal neuritis of the cervical and paraspinal nerves following treatment with ipilimumab and radiation therapy.

How to promote and preserve eyelid health.

PubMed

Benitez-Del-Castillo, Jose M

2012-01-01

Disorders of the lacrimal functional unit are common in ophthalmological practice, with meibomian gland dysfunction, blepharitis, and dry eye forming a significant part of the general ophthalmologist's practice. The eyelid and its associated structures form a complex organ designed to protect the fragile corneal surface and improve visual acuity. This organ is subject to a number of disorders, including meibomian gland dysfunction, dry eye syndrome, anterior blepharitis, allergic and dermatological conditions, and disorders associated with contact lens use. Although commonly described separately, disorders of the lacrimal function unit are better considered as a group of interacting pathologies that have inflammatory mediators as a central feature. Eyelid hygiene, in the sense of routine cleansing and massage of the eyelids, is well accepted in the management of many disorders of the eyelid. However, a broader concept of eyelid health may be appropriate, in which eyelid cleansing is but a part of a more complete program of care that includes screening and risk assessment, patient education, and coaching. The ophthalmologist has an important role to play in helping patients persist with routine eyelid care that may be long-term or lifelong. A number of preparations exist to make routine eyelid care both more effective and more pleasant, and might also improve compliance. Several such preparations have been devised, and are being assessed in clinical studies, and appear to be effective and preferred by patients over traditional soap and water or baby shampoo.

In Situ Patrolling of Regulatory T Cells Is Essential for Protecting Autoimmune Exocrinopathy

PubMed Central

Ishimaru, Naozumi; Nitta, Takeshi; Arakaki, Rieko; Yamada, Akiko; Lipp, Martin; Takahama, Yousuke; Hayashi, Yoshio

2010-01-01

Background Migration of T cells, including regulatory T (Treg) cells, into the secondary lymph organs is critically controlled by chemokines and adhesion molecules. However, the mechanisms by which Treg cells regulate organ-specific autoimmunity via these molecules remain unclear. Although we previously reported autoimmune exocrinopathy resembling Sjögren's syndrome (SS) in the lacrimal and salivary glands from C-C chemokine receptor 7 (CCR7)-deficient mice, it is still unclear whether CCR7 signaling might specifically affect the dynamics and functions of Treg cells in vivo. We therefore investigated the cellular mechanism for suppressive function of Treg cells via CCR7 in autoimmunity using mouse models and human samples. Methods and Findings Patrolling Treg cells were detected in the exocrine organs such as lacrimal and salivary glands from normal mice that tend to be targets for autoimmunity while the Treg cells were almost undetectable in the exocrine glands of CCR7 −/− mice. In addition, we found the significantly increased retention of CD4+CD25+Foxp3+ Treg cells in the lymph nodes of CCR7 −/− mice with aging. Although Treg cell egress requires sphingosine 1-phosphate (S1P), chemotactic function to S1P of CCR7−/− Treg cells was impaired compared with that of WT Treg cells. Moreover, the in vivo suppression activity was remarkably diminished in CCR7 −/− Treg cells in the model where Treg cells were co-transferred with CCR7 −/− CD25-CD4+ T cells into Rag2 −/− mice. Finally, confocal analysis showed that CCR7+Treg cells were detectable in normal salivary glands while the number of CCR7+Treg cells was extremely decreased in the tissues from patients with Sjögren's syndrome. Conclusions These results indicate that CCR7 essentially governs the patrolling functions of Treg cells by controlling the traffic to the exocrine organs for protecting autoimmunity. Characterization of this cellular mechanism could have clinical implications by supporting development of new diagnosis or treatments for the organ-specific autoimmune diseases such as Sjögren's syndrome and clarifying how the local immune system regulates autoimmunity. PMID:20052419

P63 Positive Mucoepidermoid Tumor of the Lacrimal Sac with Associated Papilloma.

PubMed

Iordanous, Yiannis; Belrose, Jillian C; Cadieux, Dani C; Chakrabarti, Subrata; Farmer, James P; Allen, Larry H

2015-01-01

We report a case of a 44-year-old man who presented with a left medial canthal mass and epiphora. Imaging was suggestive of a mass continuous with the nasolacrimal sac. Subsequent surgical exploration revealed a mass adherent to bone with invasion of the lacrimal system. Histological examination revealed a squamous/transitional cell papilloma overlying a low-grade mucoepidermoid carcinoma (MEC). Complete surgical resection was completed and pathology confirmed the diagnosis. This is the first case in which a MEC has been reported concurrently with an overlying papilloma, providing support for the hypothesis that MECs arise from papillomas in the lacrimal sac. Additionally, the tissue stained positive for p63, which is congruent with MEC immunoreactivity in the salivary gland. The description of these unique histopathological findings may assist in definitive diagnosis and improve our understanding of the pathophysiology underlying lacrimal sac MEC tumors.

Ocular surface immunity: homeostatic mechanisms and their disruption in dry eye disease.

PubMed

Barabino, Stefano; Chen, Yihe; Chauhan, Sunil; Dana, Reza

2012-05-01

The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others' studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ocular Surface Immunity: Homeostatic Mechanisms and Their Disruption in Dry Eye Disease

PubMed Central

Barabino, Stefano; Chen, Yihe; Chauhan, Sunil; Dana, Reza

2012-01-01

The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others’ studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. PMID:22426080

Establishment of an appropriate animal model for lacritin studies: cloning and characterization of lacritin in monkey eyes.

PubMed

Nakajima, T; Walkup, R D; Tochigi, A; Shearer, T R; Azuma, M

2007-11-01

Lacritin is a mitogen of human salivary gland cells as well as a stimulator of human corneal epithelial cells. It is expected to be an important factor in maintaining the surrounding ocular surface. The monkey would be a relevant animal model in which to study the role of lacritin in ophthalmic physiology and pathology. However, to our knowledge, no cDNA cloning or functional analysis of monkey lacritin has been performed. Thus, the purposes of this study were: (1) to clone the monkey ortholog of lacritin; (2) to characterize lacritin in tears from several species; and (3) to determine the tissues where lacritin is produced and secreted. cDNA for lacritin from rhesus macaque contained 547 bp, with 411 bp in an open reading frame (ORF) encoding a protein of 137 amino acids. Monkey lacritin showed 89% amino acid homology with human lacritin; one amino acid was deleted in all three monkey strains. The predicted MW of mature lacritin was 12.2 kDa, and the isoelectric point was 4.99. Lacritin showed anomalous migration at approximately 21.0 kDa on SDS-PAGE, as confirmed by immunoblotting and amino acid sequencing. Similar to native lacritin in monkey tears, a 21 kDa band was also detected in human tears. In contrast, no lacritin was observed at a similar position on SDS-PAGE in rat, rabbit and dog tears. In the monkey, lacritin mRNA was expressed highly in the lacrimal gland, moderately in the conjunctiva and the meibomian gland, and weakly in corneal epithelium. In primates, lacritin was produced in the lacrimal gland and secreted into tear fluid. These results suggest that lacritin might be important for the maintenance of the ocular surface in higher animals, such as monkeys and humans.

Not All Lacrimal Epithelial Cells are Created Equal—Heterogeneity of the Rabbit Lacrimal Gland and Differential Secretion

PubMed Central

Ding, Chuanqing; Huang, Jianyan; MacVeigh-Aloni, Michelle; Lu, Michael

2013-01-01

Aims To test the hypotheses that some epithelial cells in the rabbit lacrimal gland (LG) are mucin-secreting cells that are also particularly rich in aquaporin 5 (AQP5) and sodium potassium ATPase β1 subunit (NKAβ1), LG-secreted mucins contribute to the total mucin pool in tear film, and that the rabbit LG is a heterogenic gland where proteins secreted in response to different agonists are varied. Materials and methods LGs were obtained from adult female rabbits and processed for paraffin sections for hematoxylin and eosin (HE) staining, periodic acid-Schiff (PAS), mucicarmine, and Alcian blue (pH 0.4, 1.0, and 2.5) for the detection of mucins. Serial sections were used for immunohistochemistry (IHC) and PAS. LG lysates and fluids were assayed by dot blot for detection of mucins, and by SDS-PAGE to detect differences in protein profiles of LG fluids stimulated by different agonists. Results HE staining demonstrated that the LG is a heterogeneous gland where most epithelial cells are serous, while all duct cells are mucous cells. Some acini and individual acinar cells within serous acini are also mucous or seromucous cells and these cells are particularly rich in AQP5 and NKAβ1. Dot blot assay showed the presence of mucins in the LG fluids. The protein profiles of LG fluids from pilocarpine, phenylephrine, and isoproterenol varied significantly, particularly in the mid range. Conclusions Our data indicated that the rabbit LG is a heterogeneous gland that is composed of both serous and mucin-secreting cells, and mucins produced by the LG contribute to the mucin pool in the tear film. The heterogeneity of the rabbit LG supports the notion of differential secretion, i.e. the volume and composition of the LG fluids vary depending on various circumstances in the ocular surface and the body’s needs. PMID:21999223

Gene Expression Profiling and Heterogeneity of Nonspecific Orbital Inflammation Affecting the Lacrimal Gland.

PubMed

Rosenbaum, James T; Choi, Dongseok; Harrington, Christina A; Wilson, David J; Grossniklaus, Hans E; Sibley, Cailin H; Salek, Sherveen S; Ng, John D; Dailey, Roger A; Steele, Eric A; Hayek, Brent; Craven, Caroline M; Edward, Deepak P; Maktabi, Azza M Y; Al Hussain, Hailah; White, Valerie A; Dolman, Peter J; Czyz, Craig N; Foster, Jill A; Harris, Gerald J; Bee, Youn-Shen; Tse, David T; Alabiad, Chrisfouad R; Dubovy, Sander R; Kazim, Michael; Selva, Dinesh; Yeatts, R Patrick; Korn, Bobby S; Kikkawa, Don O; Silkiss, Rona Z; Sivak-Callcott, Jennifer A; Stauffer, Patrick; Planck, Stephen R

2017-11-01

Although a variety of well-characterized diseases, such as sarcoidosis and granulomatosis with polyangiitis, affect the lacrimal gland, many patients with dacryoadenitis are diagnosed as having nonspecific orbital inflammation (NSOI) on the basis of histology and systemic disease evaluation. The ability to further classify the disease in these patients should facilitate selection of effective therapies. To test the a priori hypothesis that gene expression profiles would complement clinical and histopathologic evaluations in identifying well-characterized diseases and in subdividing NSOI into clinically relevant groups. In this cohort study, gene expression levels in biopsy specimens of inflamed and control lacrimal glands were measured with microarrays. Stained sections of the same biopsy specimens were used for evaluation of histopathology. Tissue samples of patients were obtained from oculoplastic surgeons at 7 international centers representing 4 countries (United States, Saudi Arabia, Canada, and Taiwan). Gene expression analysis was done at Oregon Health & Science University. Participants were 48 patients, including 3 with granulomatosis with polyangiitis, 28 with NSOI, 7 with sarcoidosis, 4 with thyroid eye disease, and 6 healthy controls. The study dates were March 2012 to April 2017. The primary outcome was subdivision of biopsy specimens based on gene expression of a published list of approximately 40 differentially expressed transcripts in blood, lacrimal gland, and orbital adipose tissue from patients with sarcoidosis. Stained sections were evaluated for inflammation (none, mild, moderate, or marked), granulomas, nodules, or fibrosis by 2 independent ocular pathologists masked to the clinical diagnosis. Among 48 patients (mean [SD] age, 41.6 [19.0] years; 32 [67%] female), the mclust algorithm segregated the biopsy specimens into 4 subsets, with the differences illustrated by a heat map and multidimensional scaling plots. Most of the sarcoidosis biopsy specimens were in subset 1, which had the highest granuloma score. Three NSOI biopsy specimens in subset 1 had no apparent granulomas. Thirty-two percent (9 of 28) of the NSOI biopsy specimens could not be distinguished from biopsy specimens of healthy controls in subset 4, while other examples of NSOI tended to group with gene expression resembling granulomatosis with polyangiitis or thyroid eye disease. The 4 subsets could also be partially differentiated by their fibrosis, granulomas, and inflammation pathology scores but not their lymphoid nodule scores. Gene expression profiling discloses clear heterogeneity among patients with lacrimal inflammatory disease. Comparison of the expression profiles suggests that a subset of patients with nonspecific dacryoadenitis might have a limited form of sarcoidosis, while other patients with NSOI cannot be distinguished from healthy controls.

Canine lobular orbital adenoma: a report of 15 cases with distinctive features.

PubMed

Headrick, Jason F; Bentley, Ellison; Dubielzig, Richard R

2004-01-01

To describe a unique orbital neoplasm in dogs, of lacrimal or salivary gland origin. Fifteen dogs with lesions consistent with a diagnosis of lobular adenomas involving the orbit were identified from the Comparative Ophthalmic Pathology Laboratory of Wisconsin from 1994 to 2001. The neoplasm occurred in nine females and six males. Affected dogs ranged in age from 7 to 17 years (mean = 9.7 years). Follow-up information was available for 13 of the 15 cases. The clinical presentation included swollen/hyperemic eyelids (4/15), third eyelid protrusion (3/15), conjunctival mass (6/15), exophthalmos (4/15), resistance to retropulsion (2/15), or strabismus (1/15). In 13 cases the masses were composed of nodular, friable tissue and they were solid in two cases. Histologically, the tissue was found in encapsulated lobules resembling well differentiated lacrimal or salivary glands but completely lacking ducts. Granular PAS-positive material was found within the cytoplasm. There was recurrence in 10 of the 13 cases available for follow-up. Of those cases in which enucleation or exenteration was performed (3/15), there was recurrence of disease in one case. In three cases the dogs were euthanized before recurrence at 3 months, 5 months and 3 years post surgery. None of the deaths was related to the tumor. In the 15 cases reviewed, lobular adenomas of the orbit presented clinically and histologically as a benign neoplasm of lacrimal or salivary gland origin. Recurrence was likely unless the mass was completely excised, at times requiring orbital exenteration.

Functional anatomy and immunological interactions of ocular surface and adnexa.

PubMed

Paulsen, Friedrich

2008-01-01

This chapter gives an overview about the structures and physiology of the ocular surface and its adnexa and focuses in a second part on the possible meaning of eye-associated lymphoid tissue (EALT) in a context with the development of dry eye. Sections deal with (1) anatomy of the ocular surface, lacrimal gland, eyelid and nasolacrimal ducts. (2) The meaning and importance of the lacrimal functional unit and the function of the mucosal innate immune system are briefly summarized. (3) Finally, the occurrence and the possible function of EALT is discussed with regard to tolerance induction and dry eye. The epithelial surface of the eye and its specialized glandular infoldings produce the components of the tear film, which include water, protective antimicrobials, cytokines, lipids as well as mucins and trefoil factor family (TFF) peptides. Antimicrobials, mucins and TFF peptides perform a number of essential functions which, collectively, provide protection of the ocular surface. Their production changes in cases of dry eye. The development of EALT is a common feature frequently occurring in symptomatically normal conjunctiva and nasolacrimal ducts. The production of antimicrobials, mucins and TFF peptides can be linked with cell signaling, tear film rheology, and antimicrobial defense at the ocular surface. Changes in the production of such peptides and proteins in cases of dry eye support the assumption that these peptides and proteins are involved in the pathophysiological events that occur at the ocular surface and lacrimal apparatus. Whether special types of bacteria, viruses, or other factors, e.g., immune deviation, are responsible for the development of EALT in humans requires further investigation in prospective and experimental studies.

Lacrimal gland tumor

MedlinePlus

... Abeloff's Clinical Oncology . 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 67. Yanoff M, Cameron JD. Diseases of the visual system. In: ... Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 423. Review ... Benign Tumors Read more Eye Cancer ...

The Effect of the Aqueous Extract of Bidens Pilosa L. on Androgen Deficiency Dry Eye in Rats.

PubMed

Zhang, Chuanwei; Li, Kai; Yang, Zichao; Wang, Yuliang; Si, Haipeng

2016-01-01

Bidens pilosa L. (Bp) is widely distributed in China and has been widely used as a traditional Chinese medicine. The aim of this study was to examine the effect of the extract of Bp on androgen deficiency dry eye and determine its possible mechanisms. Twenty-four rats were randomly divided into four groups: Group Con (control), Group Sal (physiological saline), Group Fin (oral finasteride), and Group Bp (oral finasteride and Bp). The dry eye model was established in group Fin and group Bp. Aqueous tear quantity was measured with phenol red-impregnated cotton threads with anesthesia. Tear film breakup time (BUT) and corneal epithelial damage were evaluated by fluorescein staining. Animals were sacrificed at 28 days, and ocular tissues (lacrimal gland and cornea) were evaluated with light microscopy; gene microarray analysis for inflammatory cytokines and Western blot were also performed. Finasteride administration effectively induced dry eye in rats by 14 days after administration. Group Fin rats had significantly higher fluorescein staining scores and lower aqueous tear quantity and BUT than the group Con rats, and notable inflammatory cell infiltrates were observed in the lacrimal gland of group Fin rats. The fluorescein staining score, aqueous tear quantity and BUT significantly improved with Bp treatment in the group Bp rats, and the structures of the lacrimal gland were well maintained without significant lymphocyte infiltration. Cytokine antibody array data identified the cytokines B7-2/Cd86, IL-1β, IL-4, IL-6, IL-10, MMP-8, FasL, TNF-α and TIMP-1 as candidates for validation by Western blot. Expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in group Fin were upregulated compared with group Con. Levels of anti-inflammatory cytokines, such as IL-4 and IL-10, in group Fin were also upregulated compared with those in group Con. Compared with group Fin, IL-1β, FasL, and TNF-α were significantly decreased in group Bp. The extract of Bp appears to be effective for the treatment of androgen deficiency dry eye in rats by improving aqueous tear quantity, maintaining tear film stability, and inhibiting the inflammation of the lacrimal gland. © 2016 The Author(s) Published by S. Karger AG, Basel.

Gross, Histologic, and Computed Tomographic Anatomy of the Lacrimal System of Snakes

PubMed Central

Souza, Nicole M.; Maggs, David J.; Park, Shin Ae; Puchalski, Sarah; Reilly, Christopher M.; Paul-Murphy, Joanne; Murphy, Christopher J.

2014-01-01

Objective To describe the lacrimal system of snakes using contrast micro-computed tomography (micro-CT) with 3-dimensional reconstruction, fluorescein passage (“Jones”) testing, histology, and gross dissection. Animals studied One Royal Python and 19 snake cadavers representing 10 species. Procedures Direct observation following injection of fluorescein into the subspectacular space, micro-CT following injection of 3 contrast agents into the subspectacular space, gross dissection following injection of latex into the subspectacular space, and histopathology. Results Injection of fluorescein confirmed patency but not course of the lacrimal duct. Barium enabled clear visualization of the lacrimal duct whereas two iodinated contrast agents proved inadequate. Collectively, micro-CT, anatomic dissections, and histology suggest tears are produced by a single, large, serous, retrobulbar gland, released into the subspectacular space via several ductules, and drained through a single punctum originating in the ventronasal subspectacular space and the lacrimal duct taking one of 3 routes of variable tortuosity before opening into the oral cavity in close association with the opening of the duct of the vomeronasal organ. Conclusions The ophidian lacrimal duct has a generally tortuous course and the details of its anatomy is species variable. The tortuous course of the duct likely predisposes snakes to duct occlusion and must be considered when planning medical and surgical interventions in snakes with pseudobuphthalmos and subspectacular abscessation. PMID:24862081

Gross anatomy and morphometric evaluation of the canine lacrimal and third eyelid glands.

PubMed

Park, Shin Ae; Taylor, Ken T; Zwingenberger, Allison L; Reilly, Christopher M; Toupadakis, Chrisoula A; Marfurt, Carl F; Good, Kathryn L; Murphy, Christopher J

2016-05-01

The lacrimal gland (LG) and the third eyelid gland (TELG) are two intraorbital glands that, in dogs, secrete the aqueous component of the tear film. Despite the central importance of these structures for maintaining ocular surface health, the gross anatomy of the glands remains understudied. We investigated the macroscopic morphometric characteristics of the LG and TELG in three different dog breeds. Twenty-six dog heads were dissected to expose the LG and TELG; the length, width, thickness, and weight of each were measured. During the dissections, the relationships between the glands and adjacent ocular structures and the blood and nerve supplies to the LG were photo-documented. The LG had a flat and irregular shape with morphological variations among dogs. The LG was located on the dorsolateral aspect of the globe underneath the orbital ligament. The average length, width, and thickness (SEM) of the LG (mm) were 16.5 ± 0.7, 12.5 ± 0.4, and 2.7 ± 0.1 and of the TELG 10.5 ± 0.6, 11.0 ± 0.3, and 3.3 ± 0.1, respectively. The mean weights (SD) of the LG and TELG (mg) were 315.7 ± 21.1 and 263.3 ± 13.2, respectively. Beagles were observed to have significantly smaller LGs compared to pit bull terriers and pointer mixed-breed dogs. The present study provides detailed normative anatomical and morphometric data for the LG and TELG. These data will aid researchers investigating alterations induced by disease states and should inform strategies for the local delivery of pharmacologic and cellular therapeutics. © 2015 American College of Veterinary Ophthalmologists.

Epithelial Markers aSMA, Krt14, and Krt19 Unveil Elements of Murine Lacrimal Gland Morphogenesis and Maturation.

PubMed

Kuony, Alison; Michon, Frederic

2017-01-01

As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labeled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14 + population, we demonstrated that LG epithelium expansion is fuelled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the inhibition of Notch signaling prevented the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion.

Epithelial Markers aSMA, Krt14, and Krt19 Unveil Elements of Murine Lacrimal Gland Morphogenesis and Maturation

PubMed Central

Kuony, Alison; Michon, Frederic

2017-01-01

As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labeled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14+ population, we demonstrated that LG epithelium expansion is fuelled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the inhibition of Notch signaling prevented the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion. PMID:29033846

Zygomatic gland adenoma in a dog: histochemical and immunohistochemical evaluation.

PubMed

Giudice, Chiara; Marco, Rondena; Mirko, Radice; Luca, Mertel; Giorgio, Cammarata

2005-01-01

Orbital epithelial tumors in dogs are rare and most frequently malignant. Distinguishing their origin from the lacrimal or zygomatic gland is often challenging and is based mostly on tumor location. A case of adenoma involving the orbit in a 13-year-old, female, standard Schnauzer is reported. Histologically, the neoplasm was characterized by nests and cords of epithelial cells mostly forming small glandular structures. The origin of the tumor from the zygomatic gland was determined by histochemical characteristics (alcian blue pH 1 positive staining) of a small remnant of normal gland included within the tumor capsule. The benign nature of our finding was confirmed by follow-up information: 2 years after complete surgical removal of the mass no tumor recurrence or metastases was recorded.

Clinical Evaluation of a Royal Jelly Supplementation for the Restoration of Dry Eye: A Prospective Randomized Double Blind Placebo Controlled Study and an Experimental Mouse Model

PubMed Central

Inoue, Sachiko; Kawashima, Motoko; Hisamura, Ryuji; Imada, Toshihiro; Izuta, Yusuke; Nakamura, Shigeru; Ito, Masataka; Tsubota, Kazuo

2017-01-01

Background Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Lacrimal gland function has been shown to decrease with aging, a known potent risk factor for dry eye. We have previously found that orally administrated royal jelly (RJ) restored tear secretion in a rat model of dry eye. Methods and Findings We examined the effects of RJ oral administration on dry eye in this prospective, randomized, double-blind, placebo-controlled study. Forty-three Japanese patients aged 20–60 years with subjective dry eye symptoms were randomized to an RJ group (1200 mg/tablet, six tablets daily) or a placebo group for 8 weeks. Keratoconjunctival epithelial damage, tear film break-up time, tear secretion volume, meibum grade, biochemical data, and subjective dry eye symptoms based on a questionnaire were investigated at baseline, and at 4 and 8 weeks after intervention. Adverse events were reported via medical interviews. In the RJ group, tear volume significantly increased after intervention (p = 0.0009). In particular, patients with a baseline Schirmer value of ≤10 mm showed a significant increase compared with baseline volume (p = 0.0005) and volume in the placebo group (p = 0.0051). No adverse events were reported. We also investigated the effect of RJ (300 mg/kg per day) administration using a mouse model of dry eye. Orally repeated administration of RJ preserved tear secretion, potentially through direct activation of the secretory function of the lacrimal glands. Conclusion Our results suggest that RJ improves tear volume in patients with dry eye. Trial Registration Registered NO. the University Hospital Medical Information Network in Japan (UMIN000014446) PMID:28060936

Clinical Evaluation of a Royal Jelly Supplementation for the Restoration of Dry Eye: A Prospective Randomized Double Blind Placebo Controlled Study and an Experimental Mouse Model.

PubMed

Inoue, Sachiko; Kawashima, Motoko; Hisamura, Ryuji; Imada, Toshihiro; Izuta, Yusuke; Nakamura, Shigeru; Ito, Masataka; Tsubota, Kazuo

2017-01-01

Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Lacrimal gland function has been shown to decrease with aging, a known potent risk factor for dry eye. We have previously found that orally administrated royal jelly (RJ) restored tear secretion in a rat model of dry eye. We examined the effects of RJ oral administration on dry eye in this prospective, randomized, double-blind, placebo-controlled study. Forty-three Japanese patients aged 20-60 years with subjective dry eye symptoms were randomized to an RJ group (1200 mg/tablet, six tablets daily) or a placebo group for 8 weeks. Keratoconjunctival epithelial damage, tear film break-up time, tear secretion volume, meibum grade, biochemical data, and subjective dry eye symptoms based on a questionnaire were investigated at baseline, and at 4 and 8 weeks after intervention. Adverse events were reported via medical interviews. In the RJ group, tear volume significantly increased after intervention (p = 0.0009). In particular, patients with a baseline Schirmer value of ≤10 mm showed a significant increase compared with baseline volume (p = 0.0005) and volume in the placebo group (p = 0.0051). No adverse events were reported. We also investigated the effect of RJ (300 mg/kg per day) administration using a mouse model of dry eye. Orally repeated administration of RJ preserved tear secretion, potentially through direct activation of the secretory function of the lacrimal glands. Our results suggest that RJ improves tear volume in patients with dry eye. Registered NO. the University Hospital Medical Information Network in Japan (UMIN000014446).

LASIK and dry eye.

PubMed

Toda, Ikuko

2007-01-01

Dry eye is one of the most common complications after laser-assisted in situ keratomileusis (LASIK). The clinical signs of post-LASIK dry eye include positive vital staining of ocular surface, decreased tear film breakup time and Schirmer test, reduced corneal sensitivity, and decreased functional visual acuity. The symptoms and signs last at least 1 month after LASIK. Although the mechanisms for developing post-LASIK dry eye are not completely understood, loss of corneal innervation by flap-making may affect the reflex loops of the corneal-lacrimal gland, corneal-blinking, and blinking-meibomian gland, and blinking-meibomian gland, resulting in decreased aqueous and lipid tear secretion and mucin expression. As LASIK enhancement by flap-lifting induces less dry eye symptoms and signs than first surgery, it is suggested that other factors rather than loss of neurotrophic effect may be involved in the mechanisms of post-LASIK dry eye. The treatments of dry eye include artificial tears, topical cyclosporine, hot compress, punctal plugs, and autologous serum eye drops. For patients with severe preoperative dry eye, a combination of punctal plugs and serum eye drops is required to be used before surgery.

Periorbital adenocarcinoma in a bearded dragon (Pogona vitticeps).

PubMed

Darrow, Brett G; Johnstone McLean, Nancy S; Russman, Shirley E; Schiller, Chris A

2013-07-01

A 4.5-year-old female bearded dragon (Pogona vitticeps) presented for periorbital swelling affecting the left eye. A well-organized, hypoechoic mass was noted ventral and medial to the globe on ocular ultrasound. The mass continued to grow despite antibiotic therapy, and an exenteration was performed. The mass was diagnosed via histopathology and immunohistochemical staining as a probable lacrimal gland carcinoma, although a Harderian gland origin could not definitively be ruled out. The tumor recurred following removal, and the lizard died 2 months postoperatively. © 2013 American College of Veterinary Ophthalmologists.

Changes in the 7th edition of the AJCC TNM classification and recommendations for pathologic analysis of lacrimal gland tumors.

PubMed

Rootman, Jack; White, Valerie A

2009-08-01

In our recent work to update the American Joint Committee on Cancer's AJCC Cancer Staging Manual, we brought the staging system in line with that of salivary gland malignancies to better describe the range of these tumors. In addition, we have suggested that information be collected on biomarkers and clinical and histologic data points. This revised staging, along with careful histologic analysis and patient follow-up, may provide information that helps develop more targeted management for these lesions.

Tadpole-shaped lateralized parietal atretic cephalocele associated with an ipsilateral lacrimal gland fistula and schizencephalic clefts.

PubMed

Murakami, Nobuya; Morioka, Takato; Suzuki, Satoshi O; Mukae, Nobutaka; Hashiguchi, Kimiaki; Iihara, Koji

2017-02-01

Parietal atretic cephalocele (AC) and its associated intracranial venous anomalies, such as vertical embryonic positioning of the straight sinus (VEP of SS), have, in previous reports, been exclusively restricted to the midline. We report a patient with lateralized parietal AC on the right side. The AC was in the shape of a tadpole, with a large head and a long tail, extending to the proximity of the right external canthus, where a lacrimal gland fistula was observed. The superior sagittal sinus and VEP of SS were also displaced to the right side, although the sagittal suture was located at the midline. Schizencephalic clefts in the right posterior cortex were also observed. The parietal AC, which was initially located in the midline, could conceivably have been displaced to the right side by other developmental processes. However, the relationship between lateralized AC and associated multiple anomalies on the ipsilateral side is difficult to explain monogenetically. Our case study indicates that AC might have a broader spectrum of clinical symptoms than was once thought to be the case.

The ocular surface and tear film and their dysfunction in dry eye disease.

PubMed

Rolando, M; Zierhut, M

2001-03-01

The ocular surface, tear film, lacrimal glands, and eyelids act as a functional unit to preserve the quality of the refractive surface of the eye and to resist injury and protect the eye against changing bodily and environmental conditions. Events that disturb the homeostasis of this functional unit can result in a vicious cycle of ocular surface disease. The tear film is the most dynamic structure of the functional unit, and its production and turnover is essential to maintaining the health of the ocular surface. Classically, the tear film is reported to be composed of three layers: the mucin, aqueous, and lipid layers. The boundaries and real thickness of such layers is still under discussion. A dysfunction of any of these layers can result in dry eye disease.

Oral Disease Profiles in Chronic Graft versus Host Disease

PubMed Central

Fassil, H.; Mays, J.W.; Edwards, D.; Baird, K.; Steinberg, S.M.; Cowen, E.W.; Naik, H.; Datiles, M.; Stratton, P.; Gress, R.E.; Pavletic, S.Z.

2015-01-01

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer’s tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials. PMID:25740857

Detection of a human intracisternal A-type retroviral particle antigenically related to HIV

NASA Technical Reports Server (NTRS)

Garry, R. F.; Fermin, C. D.; Hart, D. J.; Alexander, S. S.; Donehower, L. A.; Luo-Zhang, H.

1990-01-01

Sjogren's syndrome is an autoimmune disease that is characterized by dryness of the mouth and eyes. The loss of salivary and lacrimal gland function is accompanied by lymphocytic infiltration. Because similar symptoms and glandular pathology are observed in certain persons infected with human immunodeficiency virus (HIV), a search was initiated for a possible retroviral etiology in this syndrome. A human intracisternal A-type retroviral particle that is antigenically related to HIV was detected in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjogren's syndrome. Comparison of this retroviral particle to HIV indicates that they are distinguishable by several ultrastructural, physical, and enzymatic criteria.

Allergic- and immunologic-mediated diseases of the eye and adnexae.

PubMed

Bistner, S

1994-07-01

Significant allergic- and immunologic-mediated diseases of the eye are reviewed. Included are diseases of the lacrimal gland namely keratoconjunctivitis sicca, immune-mediated diseases of the conjunctiva, atopic blepharoconjunctivitis, and marginal blepharitis, uveitis including lens-induced uveitis, episcleritis, orbital cellulitis, and optic neuritis. Significant diagnostic features, an approach to diagnostic workup, and treatment are presented.

Epiphora associated with dacryops in a dog.

PubMed

Grahn, B H; Mason, R A

1995-01-01

A six-month-old basset hound was presented with unilateral right epiphora and medial canthal and maxillary bone swelling. Skull radiographs and dacryocystorhinography revealed a nasal cyst, right nasolacrimal duct dilatation, and obstruction. Laboratory examination of the cyst confirmed the diagnosis of dacryops, a cyst of lacrimal gland origin. The cyst was treated successfully with surgical drainage and curettage.

TFOS DEWS II pain and sensation report

PubMed Central

Belmonte, Carlos; Nichols, Jason J.; Cox, Stephanie M.; Brock, James A.; Begley, Carolyn G.; Bereiter, David A.; Dartt, Darlene A.; Galor, Anat; Hamrah, Pedram; Ivanusic, Jason J.; Jacobs, Deborah S.; McNamara, Nancy A.; Rosenblatt, Mark I.; Stapleton, Fiona; Wolffsohn, James S.

2017-01-01

Pain associated to mechanical and chemical irritation of the eye surface is mediated by trigeminal ganglia mechano- and polymodal nociceptor neurons while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of Meibonian gland secretion or mucins release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in vivo confocal microscopy. PMID:28736339

Evolving concepts of diagnosis, pathogenesis, and therapy of Sjögren's syndrome.

PubMed

Fox, R I; Törnwall, J; Maruyama, T; Stern, M

1998-09-01

Differences in diagnostic criteria for Sjögren's Syndrome (SS) have led to confusion in the research literature and in clinical practice. A particular challenge is the clinical diagnosis of the patients with sicca symptoms, fibromyalgia, chronic fatigue, vague cognitive defects, and a low titer antinuclear antibody. Until recently, many of these patients would have been classified as primary SS using the European criteria. A suggested revision of the European criteria will require inclusion of anti SS-A antibody or characteristic minor salivary gland biopsy, leading to greater agreement between European and San Diego criteria. Recent studies have emphasized that lacrimal and salivary gland flow involves an entire "functional" unit that includes the mucosal surface (the site of inflammation), efferent nerve signals sent to the midbrain (lacrimatory and salvatory nucleus), efferent neural signals from the brain, and acinal/ductal structures in the gland. Thus, symptoms of dryness or pain can result from interferences with any part of this functional unit. The initiating antigens in SS remain unknown, but immune reactivity against SS-A, SS-B, fodrin, alpha- amylase, and carbonic anhydrase have been demonstrated in patients with established disease. The inflammatory process in the gland releases metalloproteinases that alter the relationship of epithelial cells to their matrix, an interaction that is necessary for glandular function and survival. Therapies for SS remain inadequate. In SS patients with immune-mediated extraglandular manifestation (ie, lung, kidney, skin, nerve), the therapeutic approach is similar to systemic lupus erythematosus, although these therapies have relatively little effect on tear or saliva flow.

Abnormalities in the meibomian glands in patients with oral administration of anticancer combination drug-capsule TS-1(®): a case report.

PubMed

Mizoguchi, Shin; Okada, Yuka; Kokado, Masahide; Saika, Shizuya

2015-10-24

The anticancer TS-1(®) combination capsules of tegafur, gimeracil, and oteracil potassium (Taiho Pharmaceutical Co. Ltd, Japan) causes side effects, i. e., corneal epithelial disorder and dacryostenosis. However, its side effect on meibomian gland had not been reported. We observed morphological changes in the meibomian gland in patients taking TS-1(®) who exhibited punctate corneal epithelial defects to examine if dysfunction of meibomian glands is involved in the corneal epitheliopathy. Patients comprised two males and one female (age, 59-81 years). After starting oral TS-1(®) administration, patients developed subjective symptoms such as decreased visual acuity. Corneal epithelial disorder was seen in all six eyes of the three subjects exhibited, and lacrimal duct disorder was seen in one eye. Furthermore, meibomian gland loss and contraction were observed in all six eyes that exhibited meibomian gland disorder upon examination by using the MeiboPen(®). Results suggested that oral administration of TS-1(®) may cause meibomian gland disorder which potentially affect corneal epithelial homeostasis.

[High resolution functional magnetic resonance tomography with Gd-DTPA eyedrops in diagnosis of lacrimal apparatus diseases].

PubMed

Hoffmann, K T; Anders, N; Hosten, N; Holschbach, A; Walkow, T; Sörensen, R; Hartmann, C; Felix, R

1998-08-01

Both dacryocystography and dacryoscintigraphy are well established in the evaluation of stenoses of the lacrimal drainage system. They provide limited information about the ductal anatomy itself and about periductal structures. MR imaging was evaluated for its capability to directly visualize the lacrimal drainage system in detail and simultaneously provide functional characterization of dacryostenosis. Twenty-seven lacrimal drainage systems of 23 patients suffering from epiphora were examined in an MR unit before and after conjunctival and intravenous application of Gd-DTPA using a surface coil. Dacryostenosis was found in 23 of 27 lacrimal systems. Stenoses were localized to the canalicular (n = 3), saccular (n = 8), and ductal (n = 12) level, and were classified as stenosis or occlusion. MR imaging with conjunctival contrast application allows within one examination both detailed morphological and functional assessment of the lacrimal drainage system with depiction of surrounding structures. Limitations arise mainly from demands on technical and patient-related preconditions.

Use of krypton laser stimulation in the treatment of dry eye syndrome

NASA Astrophysics Data System (ADS)

Kecik, Tadeusz; Switka-Wieclawska, Iwona; Ciszewska, Joanna; Portacha, Lidia

1991-08-01

We''d like to present the use of krypton laser stimulation in the treatment of dry eye syndrom. 10 patients with dry eye syndrom were treated with irradiation of the lacrimal gland. Schirmer test and break up time were performed before and after therapy. After 10 days of treatment we observed higher value of secreted tear amount.

Beneficial effect of daidzin in dry eye rat model through the suppression of inflammation and oxidative stress in the cornea.

PubMed

Xiao, Fan; Cui, Hua; Zhong, Xiao

2018-05-01

Present investigation evaluates the effect of daidzin in dry eye rat model through the suppression of inflammation and oxidative stress in the cornea. Briefly, electron spine resonance was used for the estimation of radical scavenging activity of daidzin and COX Fluorescent Activity Assay Kit was used for the estimation of PGS activity. Dry eye rat model was developed by removing the lacrimal gland and effect of daidzin was evaluated in dry eye rat model by estimating the fluorescein score, tear volume and expressions of heme oxigenase (HO-1), TNF α, Interlukin 6 (IL-6), matrix metallopeptidase 9 (MMP-9) and PGS-2. Result of the present study suggested that daidzin possess tyrosyl radical scavenging activity and thereby decreases the oxidative stress. Activity of PGS significantly increases in dry eye which was inhibited by daidzin treatment due to competitive inhibition of PGS. It also recovers the tear volume in dry eye rat model in which lacrimal gland was removed. Thus corneal erosion was improved by daidzin in dry eye rat model. Thus present study concludes that treatment with daidzin protects the cornea in dry eye rat model by suppression inflammation and oxidative stress.

Applications of stem cell biology to oculoplastic surgery.

PubMed

Daniel, Michael G; Wu, Albert Y

2016-09-01

The review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery. The applicability of stem cell biology varies across a range of different subfields within ophthalmology and oculoplastic surgery. Resident stem cells have been identified in the lacrimal gland, corneal limbus, orbital fat, and muscles of the eye, and can potentially be applied for in-vitro cell and organ cultures with the intent of disease modeling and transplants. The discovery of adipocyte-derived stem cells offered a potentially powerful tool for a variety of oculoplastic applications, such as wound healing, skin rejuvenation, and burn therapeutics. Several groups are currently identifying new uses for stem cells in oculoplastic surgery. The need for stem cell treatment spans a wide array of subfields within ophthalmology, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. The advent of induced pluripotent stem cells opened the realm of regenerative medicine, making the modeling of patient-specific diseases a possibility. The identification and characterization of endogenous stem cell populations in the eye makes it possible to obtain specific tissues through induced pluripotent stem cells differentiation, permitting their use in transplants for oculoplastic surgery.

Applications of stem cell biology to oculoplastic surgery

PubMed Central

Daniel, Michael G.; Wu, Albert Y.

2016-01-01

Purpose of review This review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery. Recent findings The applicability of stem cell biology varies across a range of different subfields within ophthalmology and oculoplastic surgery. Resident stem cells have been identified in the lacrimal gland, corneal limbus, orbital fat, and muscles of the eye, and can potentially be applied for in vitro cell and organ cultures with the intent of disease modeling and transplants. The discovery of adipocyte derived stem cells (ADSCs) offered a potentially powerful tool for a variety of oculoplastic applications, such as wound healing, skin rejuvenation, and burn therapeutics. Several groups are currently identifying new uses for stem cells in oculoplastic surgery. Summary The need for stem cell treatment spans a wide array of subfields within ophthalmology, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. The advent of induced pluripotent stem cells (iPSCs) opened the realm of regenerative medicine, making the modeling of patient-specific diseases a possibility. The identification and characterization of endogenous stem cell populations in the eye makes it possible to obtain specific tissues through iPSC differentiation, permitting their use in transplants for oculoplastic surgery. PMID:27206262

TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model.

PubMed

Ratay, Michelle L; Balmert, Stephen C; Acharya, Abhinav P; Greene, Ashlee C; Meyyappan, Thiagarajan; Little, Steven R

2017-12-13

Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body's own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-β1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.

Autoradiographic disposition of (1-methyl-/sup 14/C)- and (2-/sup 14/C)caffeine in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lachance, M.P.; Marlowe, C.; Waddell, W.J.

1983-11-01

Male, C57B1/6J mice received either (1-methyl-14C)caffeine or (2-14C)caffeine via the tail vein at a dose of 0.7 or 11 mg/kg, respectively. At 0.1, 0.33, 1, 3, 9, and 24 hr after treatment, the mice were anesthetized with ether and frozen by immersion in dry ice/hexane. The mice were processed for whole-body autoradiography by the Ullberg technique; this procedure does not allow thawing or contact with solvents. All autoradiographs revealed some retention of radioactivity at early time intervals in the lacrimal glands, seminal vesicle fluid, nasal and olfactory epithelium, and retinal melanocytes. The remaining portion of the animal was densitometrically uniformmore » except for the lower levels noted in the CNS and adipose tissues. Excretion of radioactivity by the liver and kidneys seems to be the major routes of elimination. Localization in the liver at late time intervals was confined principally to the centrilobular region. Late sites of retention, observed only after (1-methyl-14C)caffeine administration, included the pancreas, minor and major salivary glands, splenic red pulp, thymal cortex, bone marrow, and gastrointestinal epithelium. Sites of localization present in both studies included the olfactory epithelium, lacrimal glands, hair follicles, and retinal melanocytes. Further studies are needed to determine whether the localization at these various sites is due to metabolic degradation, active transport, or possibly a specific receptor interaction.« less

Influence of Ophthalmic Solutions on Tear Components.

PubMed

Shigeyasu, Chika; Yamada, Masakazu; Akune, Yoko

2016-11-01

Tear fluids are a mixture of secretions derived from lacrimal glands, accessory lacrimal glands, conjunctiva, and meibomian glands. Compositional changes to tears occur in the normal state and during ocular surface disease, such as dry eye conditions. We have investigated compositional changes to tears after topical application of ophthalmic solutions, with regard to tear-specific proteins (secretory immunoglobulin A, lactoferrin, lipocalin-1, and lysozyme) and ocular surface mucin in normal and dry eye conditions using high-performance liquid chromatography. After application of saline solution (0.9% sodium chloride) in normal subjects, transient but significant decreases in all tear components were observed. The recovery of protein concentrations took up to 30 minutes and lasted longer when the saline solution was applied more frequently. When applying ophthalmic solutions, a balance between washout and dilutional effects should be considered in addition to the therapeutic effect. Investigation of the effect of diquafosol solution (3%) in normal subjects revealed a significant increase in sialic acid concentration, a marker of ocular mucin, at 5 minutes after application, whereas a significant decrease was observed with saline. This result indicates the accelerated secretion of mucin from ocular tissues induced by diquafosol. A clinical study to determine the efficacy of diquafosol in patients with dry eye revealed improvements in tear breakup time, keratoconjunctival staining scores, and Schirmer test score, accompanied by an increase in sialic acid concentration in tears. Investigating normal and dry eye conditions through tear analysis may clarify the pathophysiology of dry eye conditions and support the efficacy of treatments.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models.

PubMed

Dota, Atsuyoshi; Takaoka-Shichijo, Yuko; Nakamura, Masatsugu

2013-01-01

The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models. Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model. Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score. These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.

Quality of Vision in Eyes With Epiphora Undergoing Lacrimal Passage Intubation.

PubMed

Koh, Shizuka; Inoue, Yasushi; Ochi, Shintaro; Takai, Yoshihiro; Maeda, Naoyuki; Nishida, Kohji

2017-09-01

To investigate visual function and optical quality in eyes with epiphora undergoing lacrimal passage intubation. Prospective case series. Thirty-four eyes of 30 patients with lacrimal passage obstruction were enrolled. Before and 1 month after lacrimal passage intubation, functional visual acuity (FVA), higher-order aberrations (HOAs), lower tear meniscus, and tear clearance were assessed. An FVA measurement system was used to examine changes in continuous visual acuity (VA) over time, and visual function parameters such as FVA, visual maintenance ratio, and blink frequency were obtained. Sequential ocular HOAs were measured for 10 seconds after the blink using a wavefront sensor. Aberration data were analyzed in the central 4 mm for coma-like, spherical-like, and total HOAs. Fluctuation and stability indices of the total HOAs over time were calculated. Lower tear meniscus was assessed by anterior segment optical coherence tomography. After lacrimal passage intubation, visual function significantly improved, as indicated by improved FVA (P = .003) and visual maintenance ratio (P < .001). Blink frequency decreased significantly after treatment (P = .01). Optical quality significantly improved, as indicated by a decrease in coma-like aberrations (P = .003), spherical-like aberrations (P = .018), and total HOAs (P = .001). Stability index increased (P < .001) and fluctuation index decreased (P = .019), and tear meniscus dimension decreased (P < .001). Lacrimal passage intubation for eyes with epiphora significantly improved visual function and optical quality via patency of the lacrimal passage. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca.

PubMed

Song, Xiu Jun; Li, De-Quan; Farley, William; Luo, Li Hui; Heuckeroth, Robert O; Milbrandt, Jeffrey; Pflugfelder, Stephen C

2003-10-01

Neurturin has been identified as a neurotrophic factor for parasympathetic neurons. Neurturin-deficient (NRTN(-/-)) mice have defective parasympathetic innervation of their lacrimal glands. This study was conducted to evaluate tear function and ocular surface phenotype in NRTN(-/-) mice. Determined by tail genomic DNA PCR, 25 NRTN(-/-) mice and 17 neurturin-normal (NRTN(+/+)) mice aged 6 weeks to 4 months were evaluated. Aqueous tear production, tear fluorescein clearance and corneal sensation were serially measured. Corneal permeability to AlexaFluor dextran (AFD; Molecular Probes, Eugene, OR) was measured by a fluorometric assay at 485 nm excitation and 530 nm emission. Histology was evaluated in PAS-stained sections. Mucin and HLA class II (IA) antigen were assessed by immunofluorescent staining. Tear IL-1beta was measured by ELISA, and tear matrix metalloproteinase (MMP)-9 by zymography. Gene expression in the corneal epithelia was analyzed by semiquantitative RT-PCR. In comparison to that in age-matched NRTN(+/+) mice, aqueous tear production, tear fluorescein clearance, and corneal sensation were significantly reduced in NRTN(-/-) mice, whereas corneal permeability to AFD was significantly increased. Immunoreactive MUC-4 and -5AC mucin and goblet cell density (P < 0.001) in the conjunctiva of NRTN(-/-) mice were lower than in NRTN(+/+) mice. The expression of MUC-1 and -4 mRNA by the corneal epithelium was reduced in NRTN(-/-) mice. There were a significantly greater number of IA antigen-positive conjunctival epithelial cells in NRTN(-/-) mice than NRTN(+/+) mice. Tear fluid IL-1beta and MMP-9 concentrations and the expression of IL-1beta, TNF-alpha, macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), and MMP-9 mRNA by the corneal epithelia were significantly increased in NRTN(-/-) mice, compared with NRTN(+/+) mice. Neurturin-deficient mice show phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca. This model supports the importance of a functional ocular surface-central nervous system-lacrimal gland sensory-autonomic neural network in maintaining ocular surface health and homeostasis.

Interactions of Rodent Coronaviruses with Cellular Receptors

DTIC Science & Technology

2016-05-08

ocular porphyrin discharges from inflamed lacrimal glands, and sneezing caused by acute rhinitis and photophobia. other changes caused by rat...hepatitis virus which share the same appearance in negative stains, recalling a solar corona , should be included in a group which they suggested...sialodacryoadenitis virus (SDAV) (Percy et al., 1989). Because of this breakthrough and the development of solid phase corona virus receptor assays in our

Pictorial essay: Orbital tuberculosis

PubMed Central

Narula, Mahender K; Chaudhary, Vikas; Baruah, Dhiraj; Kathuria, Manoj; Anand, Rama

2010-01-01

Tuberculosis of the orbit is rare, even in places where tuberculosis is endemic. The disease may involve soft tissue, the lacrimal gland, or the periosteum or bones of the orbital wall. Intracranial extension, in the form of extradural abscess, and infratemporal fossa extension has been described. This pictorial essay illustrates the imaging findings of nine histopathologically confirmed cases of orbital tuberculosis. All these patients responded to antituberculous treatment. PMID:20351984

New diagnostic and therapeutic approach to thyroid-associated orbitopathy based on applied kinesiology and homeopathic therapy.

PubMed

Moncayo, Roy; Moncayo, Helga; Ulmer, Hanno; Kainz, Hartmann

2004-08-01

To investigate pathogenetic mechanisms related to the lacrimal and lymphatic glands in patients with thyroid-associated orbitopathy (TAO), and the potential of applied kinesiology diagnosis and homeopathic therapeutic measures. Prospective. Thyroid outpatient unit and a specialized center for complementary medicine (WOMED, Innsbruck; R.M. and H.M.). Thirty-two (32) patients with TAO, 23 with a long-standing disease, and 9 showing discrete initial changes. All patients were euthyroid at the time of the investigation. Clinical investigation was done, using applied kinesiology methods. Departing from normal reacting muscles, both target organs as well as therapeutic measures were tested. Affected organs will produce a therapy localization (TL) that turns a normal muscle tone weak. Using the same approach, specific counteracting therapies (i.e., tonsillitis nosode and lymph mobilizing agents) were tested. Change of lid swelling, of ocular movement discomfort, ocular lock, tonsil reactivity and Traditional Chinese Medicine criteria including tenderness of San Yin Jiao (SP6) and tongue diagnosis were recorded in a graded fashion. Positive TL reactions were found in the submandibular tonsillar structures, the pharyngeal tonsils, the San Yin Jiao point, the lacrimal gland, and with the functional ocular lock test. Both Lymphdiaral (Pascoe, Giessen, Germany) and the homeopathic preparation chronic tonsillitis nosode at a C3 potency (Spagyra, Grödig, Austria) counteracted these changes. Both agents were used therapeutically over 3-6 months, after which all relevant parameters showed improvement. Our study demonstrates the involvement of lymphatic structures and flow in the pathogenesis of TAO. The tenderness of the San Yin Jiao point correlates to the above mentioned changes and should be included in the clinical evaluation of these patients.

Evaluation of Decellularized Porcine Jejunum as a Matrix for Lacrimal Gland Reconstruction In Vitro for Treatment of Dry Eye Syndrome.

PubMed

Massie, Isobel; Spaniol, Kristina; Barbian, Andreas; Poschmann, Gereon; Stühler, Kai; Geerling, Gerd; Metzger, Marco; Mertsch, Sonja; Schrader, Stefan

2017-10-01

Dry eye syndrome (DES) can cause blindness in severe cases, but mainly palliative treatments exist. A tissue-engineered lacrimal gland (LG) could provide a curative treatment. We aimed to evaluate decellularized porcine jejunum (SIS-Muc) as a scaffold for porcine LG epithelial cells. To evaluate SIS-Muc as a potential scaffold, basement membrane proteins in SIS-Muc and native LG were compared (immunohistochemistry [IHC]). Porcine LG epithelial cells cultured on plastic were characterized (immunocytochemistry), and their culture supernatant was compared with porcine tears (proteomics). Epithelial cells were then seeded onto SIS-Muc in either a static (cell crown) or dynamic culture (within a perfusion chamber) and metabolic (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and secretory capacities (β-hexosaminidase assay), protein expression (IHC), and ultrastructure transmission electron microscopy (TEM) compared in each. Collagen IV and laminin were found in both native LG and SIS-Muc. When cultured on plastic, LG epithelial cells expressed pan-cytokeratin, Rab3D, HexA, and produced mucins, but lysozyme and lactoferrin expression was nearly absent. Some porcine tear proteins (lipocalin-2 and lactoferrin) were found in LG epithelial cell culture supernatants. When LG cells were cultured on SIS-Muc, metabolic and β-hexosaminidase activities were greater in dynamic cultures than static cultures (P < 0.05). In both static and dynamic cultures, cells expressed pan-cytokeratin, Rab3D, lysozyme, and lactoferrin and produced mucins, and TEM revealed cell polarization at the apical surface and cell-cell and cell-scaffold contacts. SIS-Muc is a suitable scaffold for LG cell expansion and may be useful toward reconstruction of LG tissue to provide a curative treatment for DES. Dynamic culture enhances cell metabolic and functional activities.

Oral disease profiles in chronic graft versus host disease.

PubMed

Bassim, C W; Fassil, H; Mays, J W; Edwards, D; Baird, K; Steinberg, S M; Cowen, E W; Naik, H; Datiles, M; Stratton, P; Gress, R E; Pavletic, S Z

2015-04-01

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials. © International & American Associations for Dental Research 2015.

TH17 cells mediate inflammation in a novel model of spontaneous experimental autoimmune lacrimal keratoconjunctivitis with neural damage.

PubMed

Seo, Kyoung Yul; Kitamura, Kazuya; Han, Soo Jung; Kelsall, Brian

2017-09-27

Dry eye disease (DED) affects one third of the population worldwide. In prior studies, experimental autoimmune lacrimal keratoconjunctivitis (EALK) induced by desiccating stress in mice has been used as a model of DED. This model is complicated by a requirement for exogenous epithelial cell injury and administration of anticholinergic agents with broad immunologic effects. We sought to develop a novel mouse model of EALK and to demonstrate the responsible pathogenic mechanisms. CD4 + CD45RB high naive T cells with and without CD4 + CD45RB low regulatory T cells were adoptively transferred to C57BL/10 recombination-activating gene 2 (Rag2) -/- mice. The eyes, draining lymph nodes, lacrimal glands, and surrounding tissues of mice with and without spontaneous keratoconjunctivitis were evaluated for histopathologic changes, cellular infiltration, and cytokine production in tissues and isolated cells. Furthermore, the integrity of the corneal nerves was evaluated using whole-tissue immunofluorescence imaging. Gene-deficient naive T cells or RAG2-deficient hosts were evaluated to assess the roles of IFN-γ, IL-17A, and IL-23 in disease pathogenesis. Finally, cytokine levels were determined in the tears of patients with DED. EALK developed spontaneously in C57BL/10 Rag2 -/- mice after adoptive transfer of CD4 + CD45RB high naive T cells and was characterized by infiltration of CD4 + T cells, macrophages, and neutrophils. In addition to lacrimal keratoconjunctivitis, mice had damage to the corneal nerve, which connects components of the lacrimal functional unit. Pathogenic T-cell differentiation was dependent on IL-23p40 and controlled by cotransferred CD4 + CD45RB low regulatory T cells. T H 17 rather than T H 1 CD4 + cells were primarily responsible for EALK, even though levels of both IL-17 and IFN-γ were increased in inflammatory tissues, likely because of their ability to drive expression of CXC chemokines within the cornea and the subsequent influx of myeloid cells. Consistent with the findings of this model, the tears of patients with DED had increased levels of inflammatory cytokines, including IL-17A and TNF-α. We describe a novel model of spontaneous EALK that supports a role for T H 17 cells in disease pathogenesis and that will contribute to our understanding of autoimmune lacrimal keratoconjunctivitis in many human eye diseases, including DED. Copyright © 2017. Published by Elsevier Inc.

Targeting the Ca(2+) Sensor STIM1 by Exosomal Transfer of Ebv-miR-BART13-3p is Associated with Sjögren's Syndrome.

PubMed

Gallo, Alessia; Jang, Shyh-Ing; Ong, Hwei Ling; Perez, Paola; Tandon, Mayank; Ambudkar, Indu; Illei, Gabor; Alevizos, Ilias

2016-08-01

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is associated with inflammation and dysfunction of salivary and lacrimal glands. The molecular mechanism(s) underlying this exocrinopathy is not known, although the syndrome has been associated with viruses, such as the Epstein Barr Virus (EBV). We report herein that an EBV-specific microRNA (ebv-miR-BART13-3p) is significantly elevated in salivary glands (SGs) of pSS patients and we show that it targets stromal interacting molecule 1 (STIM1), a primary regulator of the store-operated Ca(2+) entry (SOCE) pathway that is essential for SG function, leading to loss of SOCE and Ca(2+)-dependent activation of NFAT. Although EBV typically infects B cells and not salivary epithelial cells, ebv-miR-BART13-3p is present in both cell types in pSS SGs. Importantly, we further demonstrate that ebv-miR-BART13-3p can be transferred from B cells to salivary epithelial cells through exosomes and it recapitulates its functional effects on calcium signaling in a model system. Published by Elsevier B.V.

Optimization and validation of an existing, surgical and robust dry eye rat model for the evaluation of therapeutic compounds.

PubMed

Joossen, Cedric; Lanckacker, Ellen; Zakaria, Nadia; Koppen, Carina; Joossens, Jurgen; Cools, Nathalie; De Meester, Ingrid; Lambeir, Anne-Marie; Delputte, Peter; Maes, Louis; Cos, Paul

2016-05-01

The aim of this research was to optimize and validate an animal model for dry eye, adopting clinically relevant evaluation parameters. Dry eye was induced in female Wistar rats by surgical removal of the exorbital lacrimal gland. The clinical manifestations of dry eye were evaluated by tear volume measurements, corneal fluorescein staining, cytokine measurements in tear fluid, MMP-9 mRNA expression and CD3(+) cell infiltration in the conjunctiva. The animal model was validated by treatment with Restasis(®) (4 weeks) and commercial dexamethasone eye drops (2 weeks). Removal of the exorbital lacrimal gland resulted in 50% decrease in tear volume and a gradual increase in corneal fluorescein staining. Elevated levels of TNF-α and IL-1α have been registered in tear fluid together with an increase in CD3(+) cells in the palpebral conjunctiva when compared to control animals. Additionally, an increase in MMP-9 mRNA expression was recorded in conjunctival tissue. Reference treatment with Restasis(®) and dexamethasone eye drops had a positive effect on all evaluation parameters, except on tear volume. This rat dry eye model was validated extensively and judged appropriate for the evaluation of novel compounds and therapeutic preparations for dry eye disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use of Adipose-Derived Mesenchymal Stem Cells in Keratoconjunctivitis Sicca in a Canine Model

PubMed Central

Villatoro, Antonio J.; Fernández, Viviana; Rico-Llanos, Gustavo A.; Becerra, José; Andrades, José A.

2015-01-01

Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is an immune-mediated multifactorial disease, with high level of prevalence in humans and dogs. Our aim in this study was to investigate the therapeutic effects of allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) implanted around the lacrimal glands in 12 dogs (24 eyes) with KCS, which is refractory to current available treatments. Schirmer tear test (STT) and ocular surface integrity were assessed at 0 (before treatment), 3, 6, and 9 months after treatment. Average STT values and all clinical signs showed a statistically significant change (P < 0.001) during the follow-up with reduction in all ocular parameters scored: ocular discharge, conjunctival hyperaemia, and corneal changes, and there were no signs of regression or worsening. Implanted cells were well tolerated and were effective reducing clinical signs of KCS with a sustained effect during the study period. None of the animals showed systemic or local complications during the study. To our knowledge, this is the first time in literature that implantation of allogeneic Ad-MSCs around lacrimal glands has been found as an effective therapeutic alternative to treat dogs with KCS. These results could reinforce a good effective solution to be extrapolated to future studies in human. PMID:25802852

Orbital Epstein-Barr Virus-Positive Polymorphic B-Cell Lymphoproliferative Disorder in an Apparently Immunocompetent Woman.

PubMed

Abendroth, Michael D; Bayerl, Michael G; Wilkinson, Michael J; Claxton, David F; Specht, Charles S

2017-12-01

We report a rare case of Epstein-Barr virus (EBV)-positive polymorphic B-cell lymphoproliferative disorder (LPD) involving the lacrimal gland of a 28-year-old, apparently immunocompetent woman. She presented with a chief complaint of orbital swelling and tenderness and was found to have a lesion involving the right lacrimal gland and distal superior and lateral rectus muscles. Histology of the lesion revealed histiocytes with pleomorphic nuclei, reactive lymphocytes, and scattered cells that resembled the Reed-Sternberg (R-S) cells of classical Hodgkin lymphoma. The R-S-like cells were positive for PAX5 and CD30 and negative for CD15, supporting a diagnosis of polymorphic B-cell LPD. In situ hybridization for EBV-encoded RNA demonstrated the presence of EBV. Most EBV-positive polymorphic B-cell LPDs are associated with immunodeficiency. However, the patient described is HIV-negative and has no identifiable defects in immunoglobulin levels or cell-mediated immunity. This raises the question of whether she has an underlying immunodeficiency resulting from subtle changes in T-cell physiology, or whether chronic EBV infection contributed to her immune dysfunction through an unclear mechanism. The orbital mass partially regressed with chemotherapy, and the patient has done well clinically with no recurrence of this EBV-LPD for over 2 years.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

PubMed Central

Dota, Atsuyoshi; Takaoka-Shichijo, Yuko; Nakamura, Masatsugu

2013-01-01

Purpose The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models. Methods Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model. Results Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score. Conclusion These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye. PMID:23386781

Time course of ocular surface and lacrimal gland changes in a new scopolamine-induced dry eye model.

PubMed

Viau, Sabrina; Maire, Marie-Annick; Pasquis, Bruno; Grégoire, Stéphane; Fourgeux, Cynthia; Acar, Niyazi; Bretillon, Lionel; Creuzot-Garcher, Catherine P; Joffre, Corinne

2008-06-01

The aim of this study was to set up an animal model of dry eye showing disturbance in several components of the lacrimal functional unit, and to describe the time course of the appearance of clinical signs and inflammatory markers. Dry eye was induced in 6-week-old female Lewis rats by a systemic and continuous delivery of scopolamine via osmotic pumps implanted subcutaneously. We first determined the appropriate dose of scopolamine (6, 12.5, or 25 mg/day) for 28 days. In a second set of experiments, we determined markers after 1, 2, 3, 7, 10, 17, or 28 days of a 12.5-mg/day dose. Clinical signs of corneal dryness were evaluated in vivo using fluorescein staining. MHC II expression and mucin Muc5AC production were detected on the conjunctival epithelium using immunostaining. The level of IL-1beta, IL-6, TNF-alpha, and IFN-gamma mRNA was evaluated by real-time polymerase chain reaction in conjunctiva and exorbital lacrimal gland (LG). Lipids were extracted from the exorbital LG for fatty acid analysis. Daily scopolamine doses of 12.5 mg and 25 mg applied for a 28-day period induced keratitis, a decrease in Muc5AC immunostaining density in the conjunctival epithelium, and modifications in the fatty acid composition of the exorbital LG. Animals treated with a 12.5-mg/day dose of scopolamine exhibited an increase in corneal fluorescein staining after 2, 10, and 28 days. All animals exhibited unilateral or bilateral keratitis after 17 days. In the conjunctival epithelium, a significant decrease in Muc5AC immunostaining density was observed at early and late time points, and MHC II expression tended to be increased after 1, 7, 10, and 28 days, without reaching statistical significance. The levels of TNF-alpha, IL-1beta and IL-6 mRNA were increased with scopolamine treatment in both conjunctiva and exorbital LG. Arachidonic acid and the Delta5 desaturase index were significantly increased in the exorbital LG of dry eye animals at each time point. This systemic and continuous scopolamine-induced model of dry eye in the rat may represent a helpful tool to investigate moderate dry eye, and makes a contribution in the field of dry eye study.

Review of autoantigens in Sjögren's syndrome: an update.

PubMed

Tong, Louis; Koh, Vanessa; Thong, Bernard Yu-Hor

2017-01-01

Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by inflammation in exocrine glands, resulting in reduced secretion of tears and saliva, manifesting as xerophthalmia and xerostomia, respectively. It is commonly associated with Sjögren's syndrome type A (Ro) and Sjögren's syndrome type B (La) antigens. However, in most patients, the identity of the triggering antigen is not known. Factors such as genetics of histocompatibility, dysregulation of T-cells, B-cells and viral infections have been implicated. Several important studies on autoantigens in pSS have been published since a review in 2012, and the aim of this review is to provide an update on further peer-reviewed original articles in this field. Oxidative damage of Ro60 antigen may explain the epitope spreading during the immune activation in pSS. Immune-mediated destruction of the muscarinic receptor-3-expressing cells has been associated with a reduction in parasympathetic function, which could cause reduced secretory function of exocrine glands. Such a process also activates reactive oxidative species and antioxidants, which are linked to the triggering of inflammatory responses. Elevated levels of kallikrein, yet another antigen present in the lacrimal gland and other tissues, are similarly involved in triggering an autoimmune T-cell response against target glands. Studying additional antigens, the platelet-selectin and vasoactive intestinal peptides, in patients with pSS can help to elucidate the origin and process of autoimmunity, or even lead to potential biomarkers. In conclusion, the understanding of autoantigens has led to exciting major advances in the biology of pSS and may influence diagnosis and management of pSS in future.

Distinct features distinguishing IgG4-related disease from multicentric Castleman’s disease

PubMed Central

Sasaki, Takanori; Akiyama, Mitsuhiro; Kaneko, Yuko; Mori, Takehiko; Yasuoka, Hidekata; Suzuki, Katsuya; Yamaoka, Kunihiro; Okamoto, Shinichiro; Takeuchi, Tsutomu

2017-01-01

Objectives Differentiating IgG4-related disease (IgG4-RD) from multicentric Castleman’s disease (MCD) is challenging because both diseases present high serum IgG4. The objective of this study is to clarify the differences in characteristics and identify a clinically useful approach to differentiate these two diseases. Methods Forty-five consecutive patients with untreated active IgG4-RD and 33 patients with MCD were included in this study, who visited our institution from January 2000 to August 2016. The clinical and laboratory findings for the patients of the two diseases were compared. Various combinations of the distinctive findings were evaluated to identify the most efficient differentiating features between IgG4-RD and MCD. Results The levels of serum IgG4 were not different between the two diseases. Orbits, lacrimal glands, salivary glands or pancreas were involved in 88.9% of IgG4-RD cases and only in 3.0% of MCD cases. All MCD cases involved lymph nodes. Atopic history was characteristic for IgG4-RD. The levels of C reactive protein (CRP) with a cut-off of 0.80 mg/dL and IgA with a cut-off of 330 mg/dL were the most distinctive. The combination of ‘Orbits, lacrimal glands, salivary glands or pancreas involvement, atopic history, or non-involvement of lymph node’ and ‘CRP ≤ 0.8 mg/dL or IgA ≤ 330 mg/dL’ yielded the probability of 97.8% in IgG4-RD, while that of 3.0 % in patients with MCD. Conclusions Our study revealed distinct features between IgG4-RD and MCD. Differentiating between the diseases based on those distinct features, including distribution of organ involvement, atopic history, levels of IgA and CRP, was a useful approach. PMID:28959455

Characteristics of Labial Gland Mesenchymal Stem Cells of Healthy Individuals and Patients with Sjögren's Syndrome: A Preliminary Study.

PubMed

Wang, Shi-Qin; Wang, Yi-Xiang; Hua, Hong

2017-08-15

Sjögren's syndrome (SS) is a systemic autoimmune disease that is characterized by focal lymphocytic infiltration into exocrine organs such as salivary and lacrimal glands, resulting in dry mouth and eyes, and other systemic injuries. There is no curative clinical therapy for SS, and stem cell therapy has shown great potential in this area. The mesenchymal stem cells (MSCs) in the salivary glands of healthy individuals and in patients with SS have not been extensively studied. The aim of this study was to elucidate the characteristics of MSCs from the labial glands of healthy controls and of those from patients with SS to elucidate the related pathogenesis and to uncover potential avenues for novel clinical interventions. Labial glands from patients with SS and healthy subjects were obtained, and MSCs were isolated and cultured by using the tissue adherent method. The MSC characteristics of the cultured cells were confirmed by using morphology, proliferation, colony forming-unit (CFU) efficiency, and multipotentiality, including osteogenic, adipogenic, and salivary gland differentiation. The MSCs from the healthy controls and SS patients expressed characteristic MSC markers, including CD29, CD44, CD73, CD90, and CD105; they were negative for CD34, CD45, and CD106, and also negative for the salivary gland epithelium markers (CD49f and CD117). Labial gland MSCs from both groups were capable of osteogenic and adipogenic differentiation. The CFU efficiency and adipogenic differentiation potential of MSCs were significantly lower in the SS group compared with the healthy controls. Cells from both groups could also be induced into salivary gland-like cells. Real-time polymerase chain reaction and immunofluorescence staining showed that the gene and protein expression of AMY1, AQP5, and ZO-1 in cells from the SS group was lower than that in cells from the healthy group. Thus, MSCs from the labial glands in patients with SS could lack certain characteristics and functions, especially related to salivary secretion. These preliminary data provided insights that could lead to the development of novel therapeutic strategies for the treatment of SS.

[Observation on therapeutic effect of moxibustion with thunder-fire herbal moxa stick on xerophthalmia of oligodacrya].

PubMed

Chen, Lu-Quan

2008-08-01

To observe clinical therapeutic effect of moxibustion with thunder-fire herbal moxa stick on xerophthalmia of oligodacrya. Seventy cases were randomly divided into an observation group and a control group. The observation group (n=36) were treated with moxibustion with thunder-fire herbal moxa stick at Cuanzhu (BL 2), Yuyao (EX-HN 4), Tongziliao (GB 1), Taiyang (EX-HN 5), Sibai (ST 2), Jingming (BL 1), etc. and massage of acupoints and lacrimal gland around the eye. The control group (n=34) were treated with local dripping Leiran Diyanye. Changes of the main symptoms, tears secretion test, lacrimal membrane breaking time and corneal fluorescent staining before and after treatment were observed in the two groups. After treatment, sensation of dryness and foreign body sensation in the eye, asthenopia and gross symptoms significantly improved (P<0.01) in the two groups, and the observation group in the improvement of the sensation of dryness and foreign body sensation in the eye and the gross symptoms was better than the control group (P<0.05); tears secretion test significantly improved and was better in the observation group than that in the control group (P<0.05); lacrimal membrane breaking time and corneal fluorescent staining were improved in the two groups (P<0.05), and the improvement of lacrimal membrane breaking time in the observation group was more obvious than that in the control group (P<0.05). Moxibustion with thunder-fire herbal moxa stick has good therapeutic effect on xerophthalmia of oligodacrya.

Computed tomography of the lacrimal drainage system: retrospective study of 107 cases of dacryostenosis.

PubMed

Francis, I C; Kappagoda, M B; Cole, I E; Bank, L; Dunn, G D

1999-05-01

To evaluate the role of computed tomography in patients with dacryostenosis. One hundred seven cases of dacryostenosis (94 patients) were assessed by thorough clinical and lacrimal history and examination, and lacrimal region computerized tomography (CT). The lacrimal drainage system examination included the state and position of the puncta; Jones testing; lacrimal syringing; and, in the latter half of the study, telescopic nasal endoscopy. The patients were drawn from the hospital outpatients and private office of the operating lacrimal surgeon in this series (I.C.F.). Of the 107 cases, 79 either underwent dacryocystorhinostomy surgery or had this planned. In 14 of the 107 cases (12 patients), preoperative CT led to an alteration of patient management, usually referral to an otolaryngologist for further evaluation or treatment. In addition to the detection of two tumors extrinsic to the sac, conditions such as ethmoiditis, lacrimal sac mucoceles, soft tissue opacity in the nasolacrimal duct, gross nasal polyposis, fungal sinusitis, and a dacryolith were observed by CT. Similar to the role of functional endoscopic sinus surgery in otolaryngology, CT imaging will become increasingly important in the assessment of many patients with symptoms of lacrimal drainage obstruction.

External dacryocystorhinostomy for the treatment of epiphora in patients with patent but non-functioning lacrimal systems.

PubMed

Peter, Neena M; Pearson, Andrew R

2010-02-01

To assess the outcome of external dacryocystorhinostomies (DCRs) in patients with patent but non-functional lacrimal drainage systems and to identify any preoperative clinical or dacryocystography (DCG) and lacrimal scintigraphy (LS) factors associated with successful surgery. A retrospective study of 46 DCRs with silicone intubation performed for patients with epiphora associated with a clinically patent lacrimal drainage system. All patients underwent preoperative DCG and LS which were evaluated for presence, site and severity of delayed clearance. DCGs were also evaluated for reflux and anatomical abnormalities. Postoperative success was determined by subjective resolution of epiphora. Patients with persistent symptoms were offered Lester Jones Tube (LJT) insertion after establishment of a patent anastomosis to syringing and normal ostium on nasal endoscopy. Statistical analysis was performed using the chi2 and Fisher exact tests to determine whether there was any association between surgical outcome and preoperative resistance to lacrimal syringing, DCG and LS findings. 29 cases (63%) reported subjective surgical success after 11 months' average follow-up. There was a statistically significant association between increased resistance to syringing preoperatively and successful DCR (p=0.012). Of the 17 eyes that failed, all had patent anastomoses, and seven went on to have LJT insertion with complete resolution of symptoms. The majority of patients with patent but non-functional lacrimal drainage systems will be helped by DCR surgery, with greater success rates in those with significant reflux on preoperative syringing. For patients with residual epiphora, functional success can reach 100% with subsequent LJT insertion.

Evaluation of the adhesive properties of the cornea by means of optical coherence tomography in patients with meibomian gland dysfunction and lacrimal tear deficiency.

PubMed

Napoli, Pietro Emanuele; Coronella, Franco; Satta, Giovanni Maria; Galantuomo, Maria Silvana; Fossarello, Maurizio

2014-01-01

The aim was to determine the influence of meibomian gland dysfunction (MGD) and aqueous tear deficiency dry eye (ADDE) on the adhesive properties of the central cornea by means of optical coherence tomography (OCT), and to investigate the relationship between corneal adhesiveness and classical tear tests, as well as the reliability of results, in these lacrimal functional unit disorders. Prospective, case-control study. Twenty-eight patients with MGD and 27 patients with ADDE were studied. A group of 32 healthy subjects of similar age and gender distribution served as a control group. The adhesive properties of the anterior corneal surface were measured by OCT, based on the retention time of adhesion marker above it, in all participants. An excellent (≥5 minutes), borderline (within 3-5 minutes), fair (within 1-3 minutes) and poor (<1 minute) values of corneal adhesiveness were found, respectively, in 0%, 7.1%, 64.3% and 28.6% of MGD, in 0%, 7.4%, 63% and 29.6% of ADDE, and in 31.3%, 65.6%, 3.1% and 0% of healthy patients. The differences in time of corneal adhesiveness between MGD and healthy patients, as well as between ADDE and healthy patients, were found to be statistically significant (p<0.001; p<0.001; respectively). Conversely, no statistical significant differences between MGD and ADDE were found (p = 0.952). Data analysis revealed a statistically significant correlation between corneal adhesiveness and clinical tests of dry eye, as well as an excellent degree of inter-rater reliability and reproducibility for OCT measurements (p<0.001). ADDE and MGD share similar abnormalities on OCT imaging. Decreased adhesive properties of the anterior cornea were identified as a common feature of MGD and ADDE. This simple OCT approach may provide new clues into the mechanism and evaluation of dry eye syndrome.

Vision-related quality of life in patients undergoing silicone tube intubation for lacrimal passage obstructions.

PubMed

Kabata, Yoshiaki; Goto, Satoshi; Takahashi, Genichiro; Tsuneoka, Hiroshi

2011-07-01

To evaluate the changes in vision-related quality of life in patients with lacrimal passage obstructions undergoing silicone tube intubations. Prospective, consecutive, comparative, interventional case series. Forty-five patients with the chief complaint of epiphora diagnosed with complete and unilateral lacrimal passage obstructions were enrolled. Exclusion criteria included history of congenital nasolacrimal stenosis; lacrimal passage obstructions resulting from trauma, tumor, or chemotherapy; previous lacrimal passage surgery; and partial and functional nasolacrimal duct obstructions. Silicone tube intubation using a Nunchaku-style tube was performed under direct visualization with dacryoendoscope in all patients. Operations were considered as successful when the irrigating fluid could pass through the lacrimal passage and the disappearance of dye was observed in dye disappearance test and the patients' epiphora symptoms improved 3 months postoperatively. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was self-administered in all patients preoperatively and 3 months postoperatively. Patients' preoperative and 3-months-postoperative NEI VFQ-25 scores were compared. Operations were successful in 40 patients (89%). Fully completed questionnaires were received from 32 patients (80%). Silicone tube intubation using a Nunchaku-style tube was associated with a significant improvement of the NEI VFQ-25 composite score (P = .0001), ocular pain score (P < .0001), and mental health score (P = .0003). Relief of epiphora by silicone tube intubation using a Nunchaku-style tube treatment significantly improved the vision-related quality of life in patients with lacrimal passage obstructions. Copyright © 2011 Elsevier Inc. All rights reserved.

Altered Mucin and Glycoprotein Expression in Dry Eye Disease.

PubMed

Stephens, Denise N; McNamara, Nancy A

2015-09-01

Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial cells, and the lacrimal gland must work together to create a stable tear film. Although many studies have explored the mechanism(s) whereby mucins maintain and protect the ocular surface, the effects of dry eye on the structure and function of ocular mucins are unclear. Here, we summarize current findings regarding ocular mucins and how they are altered in dry eye. We performed a literature review of studies exploring the expression of mucins produced and/or associated with tissues that comprise the lacrimal functional unit and how they are altered in dry eye. We also summarize new insights on the immune-mediated effects of aqueous tear deficiency on ocular surface mucins that we discovered using a mouse model of dry eye. Although consistent decreases in MUC5AC and altered expression of membrane-bound mucins have been noted in both Sjögren and non-Sjögren dry eye, many reports of altered mucins in dry eye are contradictory. Mechanistic studies, including our own, suggest that changes in the glycosylation of mucins rather than the proteins themselves may occur as the direct result of local inflammation induced by proinflammatory mediators, such as interleukin-1. Altered expression of ocular mucins in dry eye varies considerably from study to study, likely attributed to inherent difficulties in analyzing small-volume tear samples, as well as differences in tear collection methods and disease severity in dry eye cohorts. To better define the functional role of ocular mucin glycosylation in the pathogenesis of dry eye disease, we propose genomic and proteomic studies along with biological pathway analysis to reveal novel avenues for exploration.

Ectodermal Differentiation of Wharton's Jelly Mesenchymal Stem Cells for Tissue Engineering and Regenerative Medicine Applications.

PubMed

Jadalannagari, Sushma; Aljitawi, Omar S

2015-06-01

Mesenchymal stem cells (MSCs) from Wharton's jelly (WJ) of the human umbilical cord are perinatal stem cells that have self-renewal ability, extended proliferation potential, immunosuppressive properties, and are accordingly excellent candidates for tissue engineering. These MSCs are unique, easily accessible, and a noncontroversial cell source of regeneration in medicine. Wharton's jelly mesenchymal stem cells (WJMSCs) are multipotent and capable of multilineage differentiation into cells like adipocytes, bone, cartilage, and skeletal muscle upon exposure to appropriate conditions. The ectoderm is one of the three primary germ layers found in the very early embryo that differentiates into the epidermis, nervous system (spine, peripheral nerves, brain), and exocrine glands (mammary, sweat, salivary, and lacrimal glands). Accumulating evidence shows that MSCs obtained from WJ have an ectodermal differentiation potential. The current review examines this differentiation potential of WJMSC into the hair follicle, skin, neurons, and sweat glands along with discussing the potential utilization of such differentiation in regenerative medicine.

Assessment and Management of Proximal and Incomplete Symptomatic Obstruction of the Lacrimal Drainage System

PubMed Central

Kashkouli, Mohsen Bahmani; Pakdel, Farzad; Kiavash, Victoria

2012-01-01

Epiphora is a common complaint of patients who present to an Ophthalmology Clinic. In many cases, epiphora is due to an obstruction in the lacrimal drainage system. However, a subgroup of symptomatic patients with epiphora has a patent lacrimal drainage system. Such cases are usually termed ‘functional obstruction’ and / or ‘stenosis of the lacrimal drainage system’. Various etiologies and diagnostic and therapeutic approaches have been described in literature, which implies the lack of a standardized approach. This article will review the evolving diagnostic and therapeutic approaches in literature, and in the end, propose a paradigm in approaching this group of patients. PMID:22346116

Local recurrence as immunoglobulin G4 (IgG4)-related disease 10 years after radiotherapy to ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

PubMed

Matsuo, Toshihiko; Ichimura, Kouichi; Yoshino, Tadashi

2011-01-01

In 2000, a 48-year-old woman developed a left orbital mass with lacrimal gland involvement and then, in 2003, a right orbital mass with lacrimal gland involvement, both of which were diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). She underwent 30 Gy external beam radiation to bilateral orbital lesions. The lymphoma cells in both lesions did not share the same clonality, as shown by amplification by polymerase chain reaction of the immunoglobulin heavy chain gene. Immunoglobulin light chain analysis by immunohistochemistry and messenger RNA in situ hybridization showed λ chain monotype in the left orbital lesion but κ chain monotype in the right orbital lesion. She developed recurrent left orbital mass with high uptake on fluorodeoxyglucose positron emission tomography fused with computed tomography in 2010, and excisional biopsy disclosed the formation of follicles and infiltration with immunoglobulin G4 (IgG4)-positive plasma cells mainly in interfollicular areas. The immunoglobulin light chain analysis showed the λ chain and κ chain bitype. With the immunohistopathological diagnosis of IgG4-related disease, the serum IgG4 level was found to show elevation at 376 mg/dL, and the patient chose observation. This is the first reported case of development of IgG4-related disease after bilataral orbital MALT lymphoma with external beam radiotherapy.

Establishment and characterization of a cell line from human adenoid cystic carcinoma of the lacrimal glands and a nude mouse transplantable model.

PubMed

Lin, Tingting; Zhu, Limin; Zhou, Beiqing; Xie, Lianfeng; Lv, Jianmei; Dong, Lijie; He, Yanjin

2015-06-01

Using tissue block culture techniques, we established a new human tumor cell line derived from adenoid cystic carcinoma of the lacrimal glands (LACC-1). The LACC-1 cell line was successfully subcultured for more than 100 passages during the last two years. The outgrowth of cells was observed by day 5 after seeding, and then the cells were generated slowly. The first passage proceeded by day 32, and the classical epithelioid cell colonies formed by day 69 after inoculation. After eight passages, homogeneous epithelioid tumor cells appeared when we combined continuous passage, mechanical scraping, repeated adherence, and dissociation methods to remove the fibroblast cells. LACC-1 cells appeared as a histologically solid pattern and continuous passage culture. The population doubling time was approximately 37.1 h. LACC-1 cells appeared as an epithelioid monolayer culture on the cell culture flask and presented with a cobblestone-like appearance when they reached confluency. The nucleus was large and round with many abnormal mitoses. The nucleoplasm ratio was high. Multinucleated tumor giant cells appeared. LACC-1 cells showed a tendency to have overlapping growth without contact inhibition when the cell density continued to increase. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the LACC-1 cells were malignant tumor cells that were poorly differentiated. The surface of the LACC-1 cells exhibited affluent microvilli, protuberances and filopodia under SEM. The no. 84 generation LACC-1 cell line was inoculated subcutaneously into the subaxillary of nude mice and the tumorigenic potential was evident. The formation rate of the transplanted tumors was 100% at day 7 after inoculation. This finding showed that the LACC-1 cell line was malignant with tumorigenic ability. The xenograft tumors retained the same histological characteristics of a solid pattern as the LACC-1 original tumor after inoculation for 49 days. Under TEM observation, the xenograft tumor cells had the same ultrastructure as the LACC-1 cells. Immunohistochemical examination revealed the similarity of both cytoskeletal proteins (e.g., cytokeratin, vimentin, desmin and α-SMA) and S-100 expression in the original tumor, LACC-1 cells and xenograft tumors. Immunoreactivity of these proteins was gradually decreased in these three tissues. Reverse transcription-polymerase chain reaction demonstrated that the xenograft tumors originated from the human. Based on these results, the LACC-1 cell line provides a useful model for studying the biological characteristics of human ACC of the lacrimal glands.

[The cultivation and identification of lacrimal gland adenoid cystic cancer stem cells].

PubMed

Lyu, Jianmei; He, Yanjin; Xie, Lianfeng; Liu, Xun; Zhu, Limin

2015-10-01

To isolate and cultivate the Lacrimal gland Adenoid Cystic Carcinoma cells line, study Cancer Stem Cells properties. Experimental study. Lacrimal gland adenoid cystic carcinoma cancer stem cells were cultivated in serum-free suspension culture and the morphological changes were observed. Cells were divided into two groups, the LACC-CSC experimental group and the LACC control group. The flow cytometry instrument was used to detect the expression of classical stem cell markers CD133 and ABCG2. Transwell chamber was used to detect the cancer stem cell aggressivity and differentiated into the vascular endothelial cells. The tumorigenic force in vitro xenotransplantation were applied. LACC cells can grow suspensively after vaccinated in serum free medium and form tumor microspheres after 10-12 days. Flow cytometry experiments showed that the expression ratio of stem cell markers CD133 in LACC-CSC was (35.67 ± 6.86)%, significantly different to LACC with (0.46 ± 0.48)%, (t = 8.867, P < 0.05). Similarly, the expression ratio of stem cell marker ABCG2 in LACC-CSC was (39.99 ± 4.54)%, significantly different to LACC with (6.75 ± 1.34)%, (t = -9.932, P < 0.05). In vitro experiment of Matrigel invasion, LACC-CSC went through the matrigel basement membrane averagely (32.60 ± 8.79)/HP contrary to LACC with average (10.20 ± 2.77)/HP after 24 hours, showing statistically significance (t = 5.433, P < 0.05) between the two groups. After training for 48 hours, the difference between two groups was still obvious (t = 5.779, P < 0.05) with LACC-CSC average (62.60 ± 4.83)/HP to LACC (44.00 ± 5.34)/HP. When induced by serum medium containing VEGF and bFGF, LACC-CSC grew adherent gradually and cell morphological changes occurred after continuous induction to long spindle cells. When cultured into three-dimensional matrix structure they formed vessel samples and expressed vascular endothelial marker CD31 and CD34. Transplanted tumor in vitro experiment, mice of LACC-CSC group grew tumors in 9 days with 100% tumorigenic rate, whereas LACC group 12 days with 100% tumorigenic rate. LACC-CSC can be obtained through serum-free culture method. LACC-CSC grew suspensively and expressed classical stem cell markers. LACC-CSC were identified as cancer stem cells with stronger migration and invasion. LACC-CSC have tumorigenic force and multi-directional differentiation potential with general characteristics of the stem cell.

Buccal drug delivery technologies for patient-centred treatment of radiation-induced xerostomia (dry mouth).

PubMed

Malallah, Osamah S; Garcia, Cristina M Aller; Proctor, Gordon B; Forbes, Ben; Royall, Paul G

2018-04-25

Radiotherapy is a life-saving treatment for head and neck cancers, but almost 100% of patients develop dry mouth (xerostomia) because of radiation-induced damage to their salivary glands. Patients with xerostomia suffer symptoms that severely affect their health as well as physical, social and emotional aspects of their life. The current management of xerostomia is the application of saliva substitutes or systemic delivery of saliva-stimulating cholinergic agents, including pilocarpine, cevimeline or bethanechol tablets. It is almost impossible for substitutes to replicate all the functional and sensory facets of natural saliva. Salivary stimulants are a better treatment option than saliva substitutes as the former induce the secretion of natural saliva from undamaged glands; typically, these are the minor salivary glands. However, patients taking cholinergic agents systemically experience pharmacology-related side effects including sweating, excessive lacrimation and gastrointestinal tract distresses. Local delivery direct to the buccal mucosa has the potential to provide rapid onset of drug action, i.e. activation of minor salivary glands within the buccal mucosa, while sparing systemic drug exposure and off-target effects. This critical review of the technologies for the local delivery of saliva-stimulating agents includes oral disintegrating tablets (ODTs), oral disintegrating films, medicated chewing gums and implantable drug delivery devices. Our analysis makes a strong case for the development of ODTs for the buccal delivery of cholinergic agents: these must be patient-friendly delivery platforms with variable loading capacities that release the drug rapidly in fluid volumes typical of residual saliva in xerostomia (0.05-0.1 mL). Copyright © 2018 Elsevier B.V. All rights reserved.

ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands

PubMed Central

Nelson, Joel W.; Leigh, Noel J.; Mellas, Rachel E.; McCall, Andrew D.; Aguirre, Alfredo

2013-01-01

Sjögren's syndrome (SS) is an autoimmune disorder characterized by chronic inflammation and destruction of salivary and lacrimal glands, leading to dry mouth, dry eyes, and the presence of anti-nuclear antibodies. Despite modern advances, the current therapies for SS have no permanent benefit. A potential treatment could involve the use of resolvins, which are highly potent endogenous lipid mediators that are synthesized during the resolution of inflammation to restore tissue homeostasis. Our previous studies indicate that ALX/FPR2, the receptor for RvD1, is expressed and active in the rat parotid cell line Par-C10. Specifically, activation of ALX/FPR2 with RvD1 blocked inflammatory signals caused by TNF-α and enhanced salivary epithelial integrity. The goal of this study was to investigate RvD1 receptor expression and signaling pathways in primary salivary cells. Additionally, we determined the role of the aspirin-triggered 17R analog (AT-RvD1, a more chemically stable RvD1 epimeric form) in prevention of TNF-α-mediated salivary inflammation in mouse submandibular glands (mSMG). Our results indicate that ALX/FPR2 is expressed in mSMG and is able to elicit intracellular Ca2+ responses and phosphorylation of Erk1/2, as well as Akt. Given that these signaling pathways are linked to cell survival, we investigated whether AT-RvD1 was able to prevent programmed cell death in mSMG. Specifically, we determined that AT-RvD1 prevented TNF-α-mediated caspase-3 activation. Finally, we show that ALX/FPR2 is expressed in human minor salivary glands with and without SS, indicating the potential therapeutic use of AT-RvD1 for this condition. PMID:24259417

ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands.

PubMed

Nelson, Joel W; Leigh, Noel J; Mellas, Rachel E; McCall, Andrew D; Aguirre, Alfredo; Baker, Olga J

2014-01-15

Sjögren's syndrome (SS) is an autoimmune disorder characterized by chronic inflammation and destruction of salivary and lacrimal glands, leading to dry mouth, dry eyes, and the presence of anti-nuclear antibodies. Despite modern advances, the current therapies for SS have no permanent benefit. A potential treatment could involve the use of resolvins, which are highly potent endogenous lipid mediators that are synthesized during the resolution of inflammation to restore tissue homeostasis. Our previous studies indicate that ALX/FPR2, the receptor for RvD1, is expressed and active in the rat parotid cell line Par-C10. Specifically, activation of ALX/FPR2 with RvD1 blocked inflammatory signals caused by TNF-α and enhanced salivary epithelial integrity. The goal of this study was to investigate RvD1 receptor expression and signaling pathways in primary salivary cells. Additionally, we determined the role of the aspirin-triggered 17R analog (AT-RvD1, a more chemically stable RvD1 epimeric form) in prevention of TNF-α-mediated salivary inflammation in mouse submandibular glands (mSMG). Our results indicate that ALX/FPR2 is expressed in mSMG and is able to elicit intracellular Ca2+ responses and phosphorylation of Erk1/2, as well as Akt. Given that these signaling pathways are linked to cell survival, we investigated whether AT-RvD1 was able to prevent programmed cell death in mSMG. Specifically, we determined that AT-RvD1 prevented TNF-α-mediated caspase-3 activation. Finally, we show that ALX/FPR2 is expressed in human minor salivary glands with and without SS, indicating the potential therapeutic use of AT-RvD1 for this condition.

Ocular Sarcoidosis

PubMed Central

Pasadhika, Sirichai; Rosenbaum, James T

2015-01-01

Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues, and may cause uveitis, episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Glaucoma and cataract can be complications from inflammation itself or adverse effects from therapy. Ophthalmic manifestations can be isolated, or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. Multi-disciplinary approaches are required to achieve the best treatment outcomes for both ocular and systemic manifestations. PMID:26593141

Transcription Factors Runx1 to 3 Are Expressed in the Lacrimal Gland Epithelium and Are Involved in Regulation of Gland Morphogenesis and Regeneration

PubMed Central

Voronov, Dmitry; Gromova, Anastasia; Liu, Daren; Zoukhri, Driss; Medvinsky, Alexander; Meech, Robyn; Makarenkova, Helen P.

2013-01-01

Purpose. Lacrimal gland (LG) morphogenesis and repair are regulated by a complex interplay of intrinsic factors (e.g., transcription factors) and extrinsic signals (e.g., soluble growth/signaling factors). Many of these interconnections remain poorly characterized. Runt-related (Runx) factors belong to a small family of heterodimeric transcription factors known to regulate lineage-specific proliferation and differentiation of stem cells. The purpose of this study was to define the expression pattern and the role of Runx proteins in LG development and regeneration. Methods. Expression of epithelial-restricted transcription factors in murine LG was examined using immunostaining, qRT-PCR, and RT2Profiler PCR microarrays. The role of Runx transcription factors in LG morphogenesis was studied using siRNA and ex vivo LG cultures. Expression of Runx transcription factors during LG regeneration was assessed using in vivo model of LG regeneration. Results. We found that Runx factors are expressed in the epithelial compartment of the LG; in particular, Runx1 was restricted to the epithelium with highest level of expression in ductal and centroacinar cells. Downregulation of Runx1 to 3 expression using Runx-specific siRNAs abolished LG growth and branching and our data suggest that Runx1, 2, and 3 are partially redundant in LG development. In siRNA-treated LG, reduction of branching correlated with reduction of epithelial proliferation, as well as expression of cyclin D1 and the putative epithelial progenitor cell marker cytokeratin-5. Runx1, Runx3, and cytokeratin-5 expression increased significantly in regenerating LG and there was modest increase in Runx2 expression during LG differentiation. Conclusions. Runx1 and 2 are new markers of the LG epithelial lineage and Runx factors are important for normal LG morphogenesis and regeneration. PMID:23532528

Immunization with 60 kD Ro peptide produces different stages of preclinical autoimmunity in a Sjögren's syndrome model among multiple strains of inbred mice.

PubMed

Kurien, B T; Dsouza, A; Igoe, A; Lee, Y J; Maier-Moore, J S; Gordon, T; Jackson, M; Scofield, R H

2013-07-01

Sjögren's syndrome is a chronic illness manifested characteristically by immune injury to the salivary and lacrimal glands, resulting in dry mouth/eyes. Anti-Ro [Sjögren's syndrome antigen A (SSA)] and anti-La [Sjögren's syndrome antigen B (SSB)] autoantibodies are found frequently in Sjögren's subjects as well as in individuals who will go on to develop the disease. Immunization of BALB/c mice with Ro60 peptides results in epitope spreading with anti-Ro and anti-La along with lymphocyte infiltration of salivary glands similar to human Sjögren's. In addition, these animals have poor salivary function/low saliva volume. In this study, we examined whether Ro-peptide immunization produces a Sjögren's-like illness in other strains of mice. BALB/c, DBA-2, PL/J, SJL/J and C57BL/6 mice were immunized with Ro60 peptide-274. Sera from these mice were studied by immunoblot and enzyme-linked immunosorbent assay for autoantibodies. Timed salivary flow was determined after pharmacological stimulation, and salivary glands were examined pathologically. We found that SJL/J mice had no immune response to the peptide from Ro60, while C57BL/6 mice produced antibodies that bound the peptide but had no epitope spreading. PL/J mice had epitope spreading to other structures of Ro60 as well as to La, but like C57BL/6 and SJL/J had no salivary gland lymphocytic infiltration and no decrement of salivary function. DBA-2 and BALB/c mice had infiltration but only BALB/c had decreased salivary function. The immunological processes leading to a Sjögren's-like illness after Ro-peptide immunization were interrupted in a stepwise fashion in these differing mice strains. These data suggest that this is a model of preclinical disease with genetic control for epitope spreading, lymphocytic infiltration and glandular dysfunction. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brualla, Lorenzo, E-mail: lorenzo.brualla@uni-due.de; Zaragoza, Francisco J.; Sempau, Josep

Purpose: External beam radiotherapy is the only conservative curative approach for Stage I non-Hodgkin lymphomas of the conjunctiva. The target volume is geometrically complex because it includes the eyeball and lid conjunctiva. Furthermore, the target volume is adjacent to radiosensitive structures, including the lens, lacrimal glands, cornea, retina, and papilla. The radiotherapy planning and optimization requires accurate calculation of the dose in these anatomical structures that are much smaller than the structures traditionally considered in radiotherapy. Neither conventional treatment planning systems nor dosimetric measurements can reliably determine the dose distribution in these small irradiated volumes. Methods and Materials: The Montemore » Carlo simulations of a Varian Clinac 2100 C/D and human eye were performed using the PENELOPE and PENEASYLINAC codes. Dose distributions and dose volume histograms were calculated for the bulbar conjunctiva, cornea, lens, retina, papilla, lacrimal gland, and anterior and posterior hemispheres. Results: The simulated results allow choosing the most adequate treatment setup configuration, which is an electron beam energy of 6 MeV with additional bolus and collimation by a cerrobend block with a central cylindrical hole of 3.0 cm diameter and central cylindrical rod of 1.0 cm diameter. Conclusions: Monte Carlo simulation is a useful method to calculate the minute dose distribution in ocular tissue and to optimize the electron irradiation technique in highly critical structures. Using a voxelized eye phantom based on patient computed tomography images, the dose distribution can be estimated with a standard statistical uncertainty of less than 2.4% in 3 min using a computing cluster with 30 cores, which makes this planning technique clinically relevant.« less

A new nonhuman primate model of severe dry eye.

PubMed

Qin, Yi; Tan, Xiaobo; Zhang, Yingnan; Jie, Ying; Labbe, Antoine; Pan, Zhiqiang

2014-05-01

The aim of this study was to establish a new rhesus monkey model of severe dry eye. A total of 8 rhesus monkeys were used for the study. Four monkeys had their main lacrimal gland and nictitating membrane surgically removed (group 1). Another 4 monkeys had a similar surgery with further application of 50% trichloroacetic acid on the bulbar conjunctiva (group 2). The ocular surface was evaluated before and after the surgery (1, 4, 8, 12, and 24 weeks) using Schirmer-1 test, corneal fluorescein staining, and the lissamine green test. Conjunctival impression cytology was also performed before and 24 weeks after the surgery. Finally, the cornea and the conjunctiva were evaluated using light microscopy. A significant decrease in tear secretion was observed in all operated eyes. Schirmer test data measured were ≤4 mm in all the operated eyes. Slit-lamp examination also revealed abnormal staining in all the operated eyes that remained stable until the end of the experiment. In group 2, corneal fluorescein staining and lissamine green test values were always ≥5 (max 12) and ≥4 (max 9), respectively. Impression cytology specimens of both the treated groups showed conjunctival squamous metaplasia and a decreased number of goblet cells. Under light microscopy, the corneal epithelium appeared irregular with edematous basal epithelial cells. The conjunctiva showed a decreased goblet cell density with infiltration of inflammatory cells. Complete removal of the principal lacrimal gland and nictitating membrane associated with the application of 50% trichloroacetic acid on the conjunctiva could induce severe dry eye in rhesus monkeys.

Graft versus host disease: what should the oculoplastic surgeon know?

PubMed

Tung, Cynthia I

2017-09-01

To provide a concise review of the oculoplastic manifestations of ocular graft versus host disease (GVHD), and to discuss their management. Ocular GVHD occurs as a common immune-mediated complication of hematopoietic stem cell transplantation that presents as a Stevens-Johnson-like syndrome in the acute phase or a Sjögren-like syndrome in the chronic phase. Cicatricial conjunctivitis may be underreported in ocular GVHD. The spectrum of oculoplastic manifestations includes GVHD of the skin, cicatricial entropion, nasolacrimal duct obstruction, and lacrimal gland dysfunction. Surgical treatment is indicated for patients with significant corneal complications from entropion. Surgical approach to repair of nasolacrimal duct obstruction is presented in this review, including modified approaches for treating patients at risk for keratitis sicca. Management of the ocular graft versus host patient may require a multidisciplinary approach involving collaboration from the oculoplastic surgeon, the corneal specialist, and the stem cell transplant physician. Oculoplastic manifestations of ocular GVHD typically present as cicatricial changes in the eyelid and lacrimal system. Careful oculoplastic and corneal evaluation are necessary when considering surgical management for the ocular GVHD patient.

Mastitis associated with Sjögren's syndrome: a series of nine cases.

PubMed

Goulabchand, Radjiv; Hafidi, Assia; Millet, Ingrid; Morel, Jacques; Lukas, Cédric; Humbert, Sébastien; Rivière, Sophie; Gény, Christian; Jorgensen, Christian; Le Quellec, Alain; Perrochia, Hélène; Guilpain, Philippe

2017-02-01

Sjögren's syndrome is well known to target exocrine glands, especially lacrimal and salivary glands, which share with mammary glands anatomical, histological, and immunological features. Herein, we investigated the mammary involvement in patients with Sjögren's syndrome and compared the histological findings with minor salivary gland involvement. We reviewed the charts of patients with Sjögren's syndrome (followed in Montpellier University Hospital, between January 2000 and January 2015), in whom minor salivary gland and mammary tissues were available. Two expert pathologists analysed retrospectively these tissues in order to identify inflammatory patterns. Immunohistochemical stainings were performed to precise leucocyte distribution. Sixteen Sjögren's syndrome patients with available salivary and breast tissue samples were included. All were women, with a median age of 60.1 ± 11.3 years at Sjögren's syndrome diagnosis. Mammary biopsy was conducted because of breast symptoms in 6 patients and following imaging screening strategies for breast cancer in 10 patients. Nine patients exhibited an inflammatory breast pattern (lymphocytic infiltrates or duct ectasia), close to minor salivary gland histological findings. Immunohistochemical stainings (n = 5) revealed B and T cell infiltrates within breast tissue, with a higher proportion of T CD4+ cells, but no IgG4-secreting plasma cells were found. This is the first series to describe breast inflammatory patterns in Sjögren's syndrome. Mastitis is in line with the classical involvement of exocrine glands in this disease. These findings are consistent with the literature data considering Sjögren's syndrome as an "autoimmune epithelitis".

Secretory glands and microvascular systems imaged in aqueous solution by atmospheric scanning electron microscopy (ASEM).

PubMed

Yamazawa, Toshiko; Nakamura, Naotoshi; Sato, Mari; Sato, Chikara

2016-12-01

Exocrine glands, e.g., salivary and pancreatic glands, play an important role in digestive enzyme secretion, while endocrine glands, e.g., pancreatic islets, secrete hormones that regulate blood glucose levels. The dysfunction of these secretory organs immediately leads to various diseases, such as diabetes or Sjögren's syndrome, by poorly understood mechanisms. Gland-related diseases have been studied by optical microscopy (OM), and at higher resolution by transmission electron microscopy (TEM) of Epon embedded samples, which necessitates hydrophobic sample pretreatment. Here, we report the direct observation of tissue in aqueous solution by atmospheric scanning electron microscopy (ASEM). Salivary glands, lacrimal glands, and pancreas were fixed, sectioned into slabs, stained with phosphotungstic acid (PTA), and inspected in radical scavenger d-glucose solution from below by an inverted scanning electron microscopy (SEM), guided by optical microscopy from above to target the tissue substructures. A 2- to 3-µm specimen thickness was visualized by the SEM. In secretory cells, cytoplasmic vesicles and other organelles were clearly imaged at high resolution, and the former could be classified according to the degree of PTA staining. In islets of Langerhans, the microvascular system used as an outlet by the secretory cells was also clearly observed. Microvascular system is also critically involved in the onset of diabetic complications and was clearly visible in subcutaneous tissue imaged by ASEM. The results suggest the use of in-solution ASEM for histology and to study vesicle secretion systems. Further, the high-throughput of ASEM makes it a potential tool for the diagnosis of exocrine and endocrine-related diseases. © 2016 Wiley Periodicals, Inc.

Efficacy of topical nerve growth factor treatment in dogs affected by dry eye.

PubMed

Coassin, Marco; Lambiase, Alessandro; Costa, Nicola; De Gregorio, Alessandra; Sgrulletta, Roberto; Sacchetti, Marta; Aloe, Luigi; Bonini, Stefano

2005-02-01

Preliminary data show that nerve growth factor (NGF) may improve tear production in humans. We evaluated the efficacy of topical NGF treatment in dogs who developed dry eye after the excision of the third eyelid lacrimal gland. English Bulldogs (2- to 6-year-old males and females) that had undergone the surgical removal of the prolapsed lacrimal gland of the third eyelid in both eyes at the age of 3-6 months developed chronic keratoconjunctivitis sicca associated with a decrease of Schirmer tear test I values after at least 1 year. One eye, randomly selected, of each dog was treated twice daily with 100 microl of NGF ointment for 1 month, while the fellow eye was used as control and treated with the ointment vehicle only. At baseline and after 1 month of NGF treatment the following examinations were performed: corneal evaluation by slit lamp, fluorescein staining, Schirmer tear test I, tear ferning test, corneal esthesiometry by cotton swab and conjunctival impression cytology. Topical application of NGF caused a significant improvement of all the evaluated parameters compared with baseline values. In contrast, in the control eyes there was no significant difference between the values measured before and after treatment. In particular, after NGF treatment superficial punctate keratopathy was resolved, corneal haze was reduced from stage 4 to stage 2 and Schirmer test values increased (17.2+/-1.7 mm/min vs 4.5+/-1.3 mm/min; p<0.05), as did the tear mucous component (as demonstrated by ferning test: 2.0+/-0.0 vs 4.0+/-0.0; p<0.05); conjunctival impression cytology evaluation demonstrated the presence of numerous mucous filaments and a significant increase in conjunctival goblet cell density (102.7+/-68.3 vs. 18.2+/-14.3 cell x field; p<0.05). Topical NGF treatment improved corneal sensitivity in two of three eyes. This open study suggests that topical application of NGF may enhance the production and functional characteristics in tear film, with an improvement of ocular surface signs in dogs with surgically induced dry eye. These results suggest the possibility of performing further, larger, controlled studies.

Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland

PubMed Central

Sanderson, Julie; Dartt, Darlene A.; Trinkaus-Randall, Vickery; Pintor, Jesus; Civan, Mortimer M.; Delamere, Nicholas A.; Fletcher, Erica L.; Salt, Thomas E.; Grosche, Antje; Mitchell, Claire H.

2014-01-01

This review highlights recent findings that describe how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca2+ concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in Müller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target may be a key issue in understanding how physiological signaling becomes pathological in ocular disease. PMID:25151301

Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study.

PubMed

Weber, Damien C; Bogner, Joachim; Verwey, Jorn; Georg, Dietmar; Dieckmann, Karin; Escudé, Lluis; Caro, Monica; Pötter, Richard; Goitein, Gudrun; Lomax, Antony J; Miralbell, Raymond

2005-10-01

A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. Target coverage of all simulated uveal melanomas was equally conformal with the photon and proton modalities. The median CI(95%) value was 1.74, 1.86, and 1.83 for the static, dynamic, and IMSRT plans, respectively. With proton planning, the median CI(95%) was 1.88 for OPTIS and substantially improved with IMPT in some tumor cases (median CI(95%), 1.29). The tumor dose homogeneity in the proton plans was, however, always better than with SRT photon planning (median inhomogeneity coefficient 0.1 and 0.15 vs. 0.46, 0.41, and 0.23 for the OPTIS and IMPT vs. the static, dynamic, and IMSRT plans, respectively). Compared with the photon plans, the use of protons did not lead to a substantial reduction in the homolateral OAR total integral dose in the low- to high-dose level, except for the lacrimal gland. The median maximal dose and dose at the 10% volume with the static, dynamic, and IMSRT plans was 33-30.8, 31.8-28, and 35.8-49 Gy, respectively, for the lacrimal gland, a critical organ. For protons, only the OPTIS plans were better, with a median maximal dose and dose at the 10% volume using OPTIS and IMPT of 19.2 and 8.8 and 25.6 and 23.6 CGE, respectively. The contralateral OARs were completely spared with the proton plans, but the median dose delivered to these structures was 1.2 Gy (range, 0-6.3 Gy) with the SRT photon plans. These results suggest that the use of SRT photon techniques, compared with protons, can result in similar levels of dose conformation. IMPT did not increase the degree of conformality for this small tumor. Tumor dose inhomogeneity was, however, always increased with photon planning. Except for the lacrimal gland, the use of protons, with or without intensity modulation, did not increase homolateral OAR dose sparing. The dose to all the contralateral OARs was, however, completely eliminated with proton planning.

Acinic cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

PubMed

Fukuzawa, Ryuji; Fukuzawa, Kazuhiro; Abe, Hitoshi; Nagai, Toshihiro; Kameyama, Kaori

2004-01-01

A male African pygmy hedgehog (Atelerix albiventris), estimated to be 3 years old, presented with exophthalmos and fixed abduction of the right eye. Radiographic examination revealed a retrobulbar tumor in the right orbital cavity. The mass was surgically resected but recurred 3 months later and the hedgehog died. There was no gross or microscopic evidence of salivary or lacrimal gland involvement of the tumor at surgery or at necropsy. The histopathologic, immunohistochemical, and ultrastructural findings were those of acinic cell carcinoma, the origin of which was unknown. This is the first known case of acinic cell carcinoma in an African hedgehog.

The Relation Between Light-Induced Lacrimation and the Melanopsin-Driven Postillumination Pupil Response.

PubMed

Lei, Shaobo; Goltz, Herbert C; Chen, Xingqiao; Zivcevska, Marija; Wong, Agnes M F

2017-03-01

To investigate the chromatic characteristics and intensity-response function of light-induced reflex lacrimation and its correlation with the melanopsin-driven postillumination pupil response (PIPR). Eleven visually normal participants completed the experiment. Lacrimation was measured in one eye by placing a calibrated filter paper strip in the conjunctival sac over a 1 minute-interval (Schirmer's test) during which participants received either no light stimulation (baseline trial) or one flash of blue or red light stimuli presented binocularly with a Ganzfeld stimulator, while the pupil response was recorded simultaneously from the fellow eye by using an eye tracker. Light stimulation trials were presented in alternating fashion at seven incremental intensity steps (0.1, 1, 3.16, 10, 31.6, 100, and 400 cd/m2). Postillumination pupil response was defined as the mean pupil constriction from 10 to 30 seconds post illumination. The amount of lacrimation in response to 10 to 400 cd/m2 blue light was significantly greater than baseline and increased monotonically with increasing light intensity. Red light did not induce significant reflex lacrimation until the brightest stimulation at 400 cd/m2. There was a positive linear correlation between PIPR and lacrimation in response to blue light (r = 0.74, P < 0.001) but not to red light (r = 0.13, P = 0.25). The chromatic characteristics and intensity-response of light-induced lacrimation are highly consistent with the features of melanopsin phototransduction. This finding is the first in vivo evidence in humans, supporting the hypothesis that light-induced reflex lacrimation is mediated primarily by melanopsin photoactivity, and provides new insight into the putative mechanisms of photophobia.

Identification of AQP5 in lipid rafts and its translocation to apical membranes by activation of M3 mAChRs in interlobular ducts of rat parotid gland.

PubMed

Ishikawa, Yasuko; Yuan, Zhenfang; Inoue, Noriko; Skowronski, Mariusz T; Nakae, Yoshiko; Shono, Masayuki; Cho, Gota; Yasui, Masato; Agre, Peter; Nielsen, Søren

2005-11-01

Aquaporin-5 (AQP5), an apical plasma membrane (APM) water channel in salivary glands, lacrimal glands, and airway epithelium, has an important role in fluid secretion. M(3) muscarinic acetylcholine receptor (mAChR)-induced changes in AQP5 localization in rat parotid glands were investigated with immunofluorescence or immunoelectron microscopy, detergent solubility, and gradient density floatation assays. Confocal microscopy revealed AQP5 localization in intracellular vesicles of interlobular duct cells in rat parotid glands and AQP5 trafficking to the APM 10 min after injection of the mAChR agonist cevimeline. Conversely, 60 min after injection, there was a diffuse pattern of AQP5 staining in the cell cytoplasm. The calcium ionophore A-23187 mimicked the effects of cevimeline. Immunoelectron microscopic studies confirmed that cevimeline induced AQP5 trafficking from intracellular structures to APMs in the interlobular duct cells of rat parotid glands. Lipid raft markers flotillin-2 and GM1 colocalized with AQP5 and moved with AQP5 in response to cevimeline. Under control conditions, the majority of AQP5 localized in the Triton X-100-insoluble fraction and floated to the light-density fraction on discontinuous density gradients. After 10-min incubation of parotid tissue slices with cevimeline or A-23187, AQP5 levels decreased in the Triton X-100-insoluble fraction and increased in the Triton X-100-soluble fraction. Thus AQP5 localizes in the intracellular lipid rafts, and M(3) mAChR activation induces AQP5 trafficking to the APM with lipid rafts via intracellular Ca(2+) signaling and induces AQP5 dissociation from lipid rafts to nonrafts on the APM in the interlobular duct cells of rat parotid glands.

Activation of Dll4/Notch Signaling and Hypoxia-Inducible Factor-1 Alpha Facilitates Lymphangiogenesis in Lacrimal Glands in Dry Eye.

PubMed

Min, Ji Hwan; Lee, Chul Hee; Ji, Yong Woo; Yeo, Areum; Noh, Hyemi; Song, Insil; Kim, Eung Kweon; Lee, Hyung Keun

2016-01-01

By using hypoxia-inducible factor-1 alpha conditional knockout (HIF-1α CKO) mice and a dry eye (DE) mouse model, we aimed to determine the role played by delta-like ligand 4 (Dll4)/Notch signaling and HIF-1α in the lymphangiogenesis of lacrimal glands (LGs). C57BL/6 mice were housed in a controlled-environment chamber for DE induction. During DE induction, the expression level of Dll4/Notch signaling and lymphangiogenesis in LGs was measured by quantitative RT-PCR, immunoblot, and immunofluorescence staining. Next, lymphangiogenesis was measured after Dll4/Notch signal inhibition by anti-Dll4 antibody or γ-secretase inhibitor. Using HIF-1α CKO mice, the expression of Dll4/Notch signaling and lymphangiogenesis in LGs of DE-induced HIF-1α CKO mice were assessed. Additionally, the infiltration of CD45+ cells in LGs was assessed by immunohistochemical (IHC) staining and flow cytometry for each condition. DE significantly upregulated Dll4/Notch and lymphangiogenesis in LGs. Inhibition of Dll4/Notch significantly suppressed lymphangiogenesis in LGs. Compared to wild-type (WT) mice, DE induced HIF-1α CKO mice showed markedly low levels of Dll4/Notch and lymphangiogenesis. Inhibition of lymphangiogenesis by Dll4/Notch suppression resulted in increased CD45+ cell infiltration in LGs. Likewise, CD45+ cells infiltrated more in the LGs of HIF-1α CKO DE mice than in non-DE HIF-1α CKO mice. Dll4/Notch signaling and HIF-1α are closely related to lymphangiogenesis in DE-induced LGs. Lymphangiogenesis stimulated by Dll4/Notch and HIF-1α may play a role in protecting LGs from DE-induced inflammation by aiding the clearance of immune cells from LGs.

Mucosal tolerance disruption favors disease progression in an extraorbital lacrimal gland excision model of murine dry eye.

PubMed

Guzmán, Mauricio; Keitelman, Irene; Sabbione, Florencia; Trevani, Analía S; Giordano, Mirta N; Galletti, Jeremías G

2016-10-01

Dry eye is a highly prevalent immune disorder characterized by a dysfunctional tear film and a Th1/Th17 T cell response at the ocular surface. The specificity of these pathogenic effector T cells remains to be determined, but auto-reactivity is considered likely. However, we have previously shown that ocular mucosal tolerance to an exogenous antigen is disrupted in a scopolamine-induced murine dry eye model and that it is actually responsible for disease progression. Here we report comparable findings in an entirely different murine model of dry eye that involves resection of the extraorbital lacrimal glands but no systemic muscarinic receptor blockade. Upon ocular instillation of ovalbumin, a delayed breakdown in mucosal tolerance to this antigen was observed in excised but not in sham-operated mice, which was mediated by interferon γ- and interleukin 17-producing antigen-specific T cells. Consistently, antigen-specific regulatory T cells were detectable in sham-operated but not in excised mice. As for other models of ocular surface disorders, epithelial activation of the NF-κB pathway by desiccating stress was determinant in the mucosal immune outcome. Underscoring the role of mucosal tolerance disruption in dry eye pathogenesis, its prevention by a topical NF-κB inhibitor led to reduced corneal damage in excised mice. Altogether these results show that surgically originated desiccating stress also initiates an abnormal Th1/Th17 T cell response to harmless exogenous antigens that reach the ocular surface. This event might actually contribute to corneal damage and challenges the conception of dry eye as a strictly autoimmune disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy of retinol palmitate eye drops for dry eye in rabbits with lacrimal gland resection

PubMed Central

Odaka, Akito; Toshida, Hiroshi; Ohta, Toshihiko; Tabuchi, Nobuhito; Koike, Daisuke; Suto, Chikako; Murakami, Akira

2012-01-01

Purpose We examined the efficacy of retinol palmitate (VApal) for dry eyes using dry eye model rabbits whose lacrimal glands were resected. Materials and methods After alkaline injury on keratoconjunctival epithelium, VApal eye drops were administered 6 times a day for 7 days. The efficacy of VApal was also compared with that of 0.1% hyaluronic acid eye drops. Results The fluorescein staining and rose bengal scores showed a significant decrease compared with the score in the vehicle group at 7 days (P < 0.05) in the 1000 IU/mL VApal group and at both 3 days (P < 0.05) and 7 days (P < 0.01) in the 1500 IU/mL VApal group. Histological examination revealed recovery of the corneal epithelium, and PAS staining disclosed the recovery of mucin-producing lower palpebral conjunctival goblet cells after 7 days in the 1500 IU/mL VApal group compared with the vehicle group. Results from impression cytology showed a significant increase in density of conjunctival goblet cells compared with that in the vehicle group after 7 days in the 1000 IU/mL VApal group and after 3 and 7 days in the 1500 IU/mL VApal group. There were no significant changes in tear flow in either group. Topical application of VApal at 1500 IU/mL showed greater improvement than 0.1% hyaluronic acid in both fluorescein and rose bengal score and in the density of conjunctival goblet cells. Conclusion It is suggested that VApal is effective for the improvement of keratoconjunctival epithelial damage associated with tear abnormalities, such as dry eyes. PMID:23055683

Multiple Natural and Experimental Inflammatory Rabbit Lacrimal Gland Phenotypes

PubMed Central

Mircheff, Austin K.; Wang, Yanru; Schechter, Joel E.; Li, Meng; Tong, Warren; Attar, Mayssa; Chengalvala, Murty; Harmuth, Joe; Prusakiewicz, Jeffery J.

2016-01-01

Purpose To investigate lacrimal gland (LG) immunophysiological and immune-mediated inflammatory process (IMIP) phenotype diversity. Methods Ex vivo matured dendritic cells (mDC) were loaded with acinar cell microparticles (MP). Peripheral blood lymphocytes (PBL) were activated in mixed cell reactions with mDC and injected directly into autologous, unilateral LG (1° ATD-LG) of two rabbit cohorts, one naïve, one immunized with a LG lysate membrane fraction (Pi). Autoimmune IgG titers were assayed by ELISA, MCR PBL stimulation indices (SI) by [3H]-thymidine incorporation. Schirmer tests without and with topical anesthetic (STT-I, STT-IA) and rose Bengal (RB) staining tests were performed. H&E and immunohistochemically stained sections were examined. RNA yields and selected transcript abundances were measured. Immune cell number and transcript abundance data were submitted to Principal Component Analysis (PCA). Results Immunizing Pi dose influenced SI but not IgG titers. STT scores were decreased, and rose Bengal scores increased, by day 118 after immunization. Previous immunization exacerbated scores in 1° ATD-eyes and exacerbated 1° ATD-LG atrophy. IMIP were evident in 2° ATD-LG as well as 1° ATD-LG. PCA described diverse immunophysiological phenotypes in control LG and diverse IMIP phenotypes in ATD-LG. IgG titers and SI pre-adoptive transfer were significantly associated with certain post-adoptive transfer IMIP phenotype features, and certain LG IMIP features were significantly associated with RB and STT IA scores. Conclusions The underlying variability of normal states may contribute to the diversity of experimental IMIP phenotypes. The ability to generate and characterize diverse phenotypes may lead to phenotype-specific diagnostic and therapeutic paradigms. PMID:27423911

Primary Sjögren's syndrome accompanied by pleural effusion: a case report and literature review.

PubMed

Ma, Dedong; Lu, Hongxiu; Qu, Yiqing; Wang, Shanshan; Ying, Yangyang; Xiao, Wei

2015-01-01

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by the infiltration of lymphocytes in exocrine glands, specifically the salivary and lacrimal glands, resulting in the typical symptoms of xerophthalmia and xerostomia. SS may be accompanied by pleural effusion when the lung is involved, but this occurrence has been reported in only 10 cases in the literature. We report the case of a 42 year-old woman with severe bilateral pleural effusion for eight years. Primary Sjögren's Syndrome was finally diagnosed based on the presence of xerophthalmia and xerostomia, biopsy of the minor salivary glands, and positive anti-SS-A antibody in the serum and pleural effusion. Biopsy of the parietal pleura through video-assisted thoracoscopy revealed infiltration of lymphocytes. The patient had a long history of pleural effusion without clear etiology. Malignant disease was first suspected because of abnormal density lesion on the left lung and malignant cells found on cytology, but PET-CT revealed no malignant lesion. Examinations did not support infection, malignant tumor, pulmonary sarcoidosis, or other connective tissue diseases. This data could be useful for the future study of pleural effusion in SS.

Contributions of ocular surface components to matrix-metalloproteinases (MMP)-2 and MMP-9 in feline tears following corneal epithelial wounding.

PubMed

Petznick, Andrea; Madigan, Michele C; Garrett, Qian; Sweeney, Deborah F; Evans, Margaret D M

2013-01-01

This study investigated ocular surface components that contribute to matrix-metalloproteinase (MMP)-2 and MMP-9 found in tears following corneal epithelial wounding. Laboratory short-haired cats underwent corneal epithelial debridement in one randomly chosen eye (n = 18). Eye-flush tears were collected at baseline and during various healing stages. Procedural control eyes (identical experimental protocol as wounded eyes except for wounding, n = 5) served as controls for tear analysis. MMP activity was analyzed in tears using gelatin zymography. MMP staining patterns were evaluated in ocular tissues using immunohistochemistry and used to determine MMP expression sites responsible for tear-derived MMPs. The proMMP-2 and proMMP-9 activity in tears was highest in wounded and procedural control eyes during epithelial migration (8 to 36 hours post-wounding). Wounded eyes showed significantly higher proMMP-9 in tears only during and after epithelial restratification (day 3 to 4 and day 7 to 28 post-wounding, respectively) as compared to procedural controls (p<0.05). Tears from wounded and procedural control eyes showed no statistical differences for pro-MMP-2 and MMP-9 (p>0.05). Immunohistochemistry showed increased MMP-2 and MMP-9 expression in the cornea during epithelial migration and wound closure. The conjunctival epithelium exhibited highest levels of both MMPs during wound closure, while MMP-9 expression was reduced in conjunctival goblet cells during corneal epithelial migration followed by complete absence of the cells during wound closure. The immunostaining for both MMPs was elevated in the lacrimal gland during corneal healing, with little/no change in the meibomian glands. Conjunctival-associated lymphoid tissue (CALT) showed weak MMP-2 and intense MMP-9 staining. Following wounding, migrating corneal epithelium contributed little to the observed MMP levels in tears. The major sources assessed in the present study for tear-derived MMP-2 and MMP-9 following corneal wounding are the lacrimal gland and CALT. Other sources included stromal keratocytes and conjunctiva with goblet cells.

Impact of Eye Cosmetics on the Eye, Adnexa, and Ocular Surface.

PubMed

Ng, Alison; Evans, Katharine; North, Rachel V; Jones, Lyndon; Purslow, Christine

2016-07-01

Despite the fact that cosmetic products undergo rigorous testing to ensure they are safe for human use, some users report mild discomfort following their application. The cutaneous changes, such as allergic dermatitis, are well reported, but the ocular changes associated with eye cosmetic use are less so. Some pigmented cosmetic products may accumulate within the lacrimal system and conjunctivae over many years of use, but immediate reports of eye discomfort after application are most common. Changes to the tear film and its stability may occur shortly after application, and contact lens wearers can also be affected by lens spoliation from cosmetic products. Additionally, creams used in the prevention of skin aging are often applied around the eyes, and retinoids present in these formulations can have negative effects on meibomian gland function and may be a contributing factor to dry eye disease. The aim of this review is to summarize current knowledge regarding the impact of cosmetic products on the eye, ocular surface, and tear film.

[Anti-M3 muscarinic acetylcholine receptor antibodies and Sjögren's syndrome].

PubMed

Tsuboi, Hiroto; Iizuka, Mana; Asashima, Hiromitsu; Sumida, Takayuki

2013-01-01

Sjögren's syndrome (SS) is an autoimmune disease that affects exocrine glands including salivary and lacrimal glands. It is characterized by lymphocytic infiltration into exocrine glands, leading to dry mouth and eyes. A number of auto-antibodies are detected in patients with SS. However, no SS-specific pathologic auto-antibodies have yet been found in this condition. M3 muscarinic acetylcholine receptor (M3R) plays a crucial role in the secretion of saliva. It is reported that some patients with SS carried inhibitory auto-antibodies against M3R. To clarify the epitopes and function of anti-M3R antibodies in SS, we examined antibodies to the extracellular domains (N terminal region, the first, second, and third extracellular loop) of M3R by ELISA using synthesized peptide antigens encoding these domains in 42 SS and 42 healthy controls (HC). Titers and positivity of anti-M3R antibodies to every extracellular domain of M3R were significantly higher in SS than in HC. Our results indicated the presence of several B cell epitopes on M3R in SS. Moreover, we analyzed the functions of anti-M3R antibodies by Ca(2+)-influx assays using a human salivary gland (HSG) cell line. The functional analysis indicated that the influence of such anti-M3R antibodies on Ca(2+)-influx in HSG cells might differ based on the epitopes to which they bind. Interestingly, both IgG from anti-M3R antibodies to the second extracellular loop positive SS and anti-M3R monoclonal antibodies against the second extracellular loop of M3R, which we generated, suppressed Ca(2+)-influx in the HSG cells induced by cevimeline stimulation. These observations suggested that auto-antibodies against the second extracellular loop of M3R could be involved in salivary dysfunction in patients with SS. These results indicated the presence of several B cell epitopes on M3R in SS and the influence of anti-M3R antibodies on salivary secretion might differ based on these epitopes. Thus, anti-M3R antibodies could be not only potential pathologic auto-antibodies, but also new diagnostic makers and therapeutic targets for SS.

Recovery of radiation-induced dry eye and corneal damage by pretreatment with adenoviral vector-mediated transfer of erythropoietin to the salivary glands in mice.

PubMed

Rocha, Eduardo M; Cotrim, Ana P; Zheng, Changyu; Riveros, Paola Perez; Baum, Bruce J; Chiorini, John A

2013-04-01

Therapeutic doses of radiation (RTx) causes dry eye syndrome (DES), dry mouth, and as in other sicca syndromes, they are incurable. The aims of this work are as follows: (a) to evaluate a mouse model of DES induced by clinically relevant doses of radiation, and (b) to evaluate the protective effect of erythropoietin (Epo) in preventing DES. C3H female mice were subjected to five sessions of RTx, with or without pre-RTx retroductal administration of the AdLTR2EF1a-hEPO (AdEpo) vector in the salivary glands (SG), and compared with naïve controls at Day 10 (10d) (8 Gy fractions) and 56 days (56d) (6 Gy fractions) after RTx treatment. Mice were tested for changes in lacrimal glands (LG), tear secretion (phenol red thread), weight, hematocrit (Hct), and markers of inflammation, as well as microvessels and oxidative damage. Tear secretion was reduced in both RTx groups, compared to controls, by 10d. This was also seen at 56d in RTx but not AdEpo+RTx group. Hct was significantly higher in all AdEpo+RTx mice at 10d and 56d. Corneal epithelium was significantly thinner at 10d in the RTx group compared with AdEpo+RTx or the control mice. There was a significant reduction at 10d in vascular endothelial growth factor (VEGF)-R2 in LG in the RTx group that was prevented in the AdEpo+RTx group. In conclusion, RTx is able to induce DES in mice. AdEpo administration protected corneal epithelia and resulted in some recovery of LG function, supporting the value of further studies using gene therapy for extraglandular diseases.

DEBS - a unification theory for dry eye and blepharitis.

PubMed

Rynerson, James M; Perry, Henry D

2016-01-01

For many years, blepharitis and dry eye disease have been thought to be two distinct diseases, and evaporative dry eye distinct from aqueous insufficiency. In this treatise, we propose a new way of looking at dry eye, both evaporative and insufficiency, as the natural sequelae of decades of chronic blepharitis. Dry eye is simply the late form and late manifestation of one disease, blepharitis. We suggest the use of a new term in describing this one chronic disease, namely dry eye blepharitis syndrome (DEBS). Bacteria colonize the lid margin within a structure known as a biofilm. The biofilm allows for population densities that initiate quorum-sensing gene activation. These newly activated gene products consist of inflammatory virulence factors, such as exotoxins, cytolytic toxins, and super-antigens, which are then present for the rest of the patient's life. The biofilm never goes away; it only thickens with age, producing increasing quantities of bacterial virulence factors, and thus, increasing inflammation. These virulence factors are likely the culprits that first cause follicular inflammation, then meibomian gland dysfunction, aqueous insufficiency, and finally, after many decades, lid destruction. We suggest that there are four stages of DEBS which correlate with the clinical manifestations of folliculitis, meibomitis, lacrimalitis, and finally lid structure damage evidenced by entropion, ectropion, and floppy eyelid syndrome. When one fully understands the structure and location of the glands within the lid, it becomes easy to understand this staged disease process. The longer a gland can resist the relentless encroachment of the invading biofilm, the longer it can maintain normal function. The stages depend purely on anatomy and years of biofilm presence. Dry eye now becomes a very easy disease to understand. We feel that dry eye should be treated and prevented by early and routine biofilm removal through electromechanical lid margin debridement.

Expression and purification of mouse peptide ESP4 in Escherichia coli.

PubMed

Hirakane, Makoto; Taniguchi, Masahiro; Yoshinaga, Sosuke; Misumi, Shogo; Terasawa, Hiroaki

2014-04-01

Pheromones are species-specific chemical signals that regulate a wide range of social and sexual behaviors in many animals. In mice, the male-specific peptide ESP1 (exocrine gland-secreting peptide 1) is secreted into tear fluids and enhances female sexual receptive behavior. ESP1 belongs to the ESP family, a multigene family with 38 genes in mice. ESP1 shares the highest homology with ESP4. ESP1 is expressed in the extraorbital lacrimal gland, whereas ESP4 is expressed in some exocrine glands. Thus, ESP4 is expected to have a function that has not been elucidated yet. Large amounts of the purified ESP4 protein are required for structural and biochemical studies. Here we present an expression and purification scheme for the recombinant ESP4 protein. The N-terminally histidine-tagged ESP4 fusion protein was expressed in Escherichia coli as inclusion bodies, which were solubilized and purified by nickel affinity chromatography. The histidine tag was cleaved with thrombin and removed by a second nickel affinity chromatography step. The ESP4 protein was isolated with high purity by reversed-phase chromatography. For NMR analyses, we prepared a stable isotope-labeled ESP4 protein. Three repeated freeze-drying steps after the reversed-phase chromatography were required, to remove a volatile contaminating compound and to obtain an NMR spectrum with a homogeneous line shape. AMS-modification and far-UV CD spectroscopic analyses suggested that ESP4 has an intramolecular disulfide bridge and a helical structure, respectively. The present study provides a powerful tool for structural and biochemical studies of ESP4, leading toward the elucidation of the roles of the ESP family members. Copyright © 2014 Elsevier Inc. All rights reserved.

Epstein-Barr virus in the enlarged salivary tissues of patients with IgG4-related disease.

PubMed

Furukawa, Takatoshi; Shimotai, Yoshitaka; Ohta, Nobuo; Ishida, Akihiro; Kurakami, Kazuya; Suzuki, Hitoshi; Yamakawa, Mitsunori; Hongo, Seiji; Kakehata, Seiji

2015-09-01

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease entity characterized by high-serum IgG4 concentration and IgG4-producing plasma cell production with fibrotic or sclerotic changes in affected organs. We aimed to clarify the roles of Epstein-Barr virus (EBV) in patients with IgG4-RDs. A retrospective clinical study at the Yamagata University School of Medicine, Yamagata, Japan. The patient group consisted of four males and four females with an average age of 62 years (range: 48-73). Expression of IgG4, latent member protein 1, EBV nuclear antigens-2, and EBV-encoded RNA in affected salivary glands from patients with IgG4-RD was examined by using immunohistochemistry and in situ hybridization. The copy number of EBV DNA in the salivary glands was also investigated by real-time polymerase chain reaction. All patients had hard masses in the salivary or lacrimal glands, or both, bilaterally. Serum concentrations of IgG4 were elevated in all cases (mean 589.1, range 129-1750), and IgG4-positive plasmacytes were observed in the involved salivary glands. Four patients developed potentially life-threatening systemic involvement after initial salivary gland swelling. EBV-associated molecules (EBNA and EBER) were overexpressed in the affected salivary glands. The copy number of EBV DNA was significantly higher in patients with potentially life-threatening systemic involvement than in patients without systemic involvement (P < 0.05). These results suggest that the copy number of EBV DNA could be useful as diagnostic findings in IgG4-RD to predict potentially life-threatening systemic involvement. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

[Psychosomatic aspects of dry eye syndrome].

PubMed

Nepp, J

2016-02-01

Patients with dry eye syndrome are known to suffer from anxiety and depression. Analysis of psychological disorders in therapy-resistant dry eye syndrome. A retrospective analysis of the training for interactive psychiatric screening (TRIPS) questionnaire from 110 patients with therapy-resistant dry eye syndrome was carried out. The results of the questionnaire allow the diagnosis of psychological disorders and vegetative disorders. Patients were divided into groups with anxiety, depression, mixed diagnoses, vegetative disorders and no diagnosis. A sicca score was used for assessment of dryness comprising the Schirmer test, measurement of tear meniscus, break up time, lipid layer thickness, the use of fluorescein and rose bengal staining tests and the subjective visual analogue scale. The diagnosis of dry eye syndrome was compared with the psychological disorders of anxiety and depression. Of the patients 52.7 % had psychological disorders with anxiety in 21.8 %, depression in 15.3 %, mixed diagnoses in 14.5 %, dystonia in 25.4 % and in 22.7 % no psychological disorders were diagnosed. General anxiety was frequent and panic disorders were often associated with other kinds of anxiety. Severe depression, such as bipolar disorder was rare. Dry eye scores were highest in the mixed group (0.59), and lowest in the group with mild anxiety (0.38). No single sicca phase disorder could be correlated with any of the psychological diagnoses. Patients with therapy-resistant dry eye syndrome often suffer from anxiety and depression. The psychological stress acts on the nervous system to suppress lacrimal gland function. Further investigation of the correlation between the lacrimal tear film phase and psychological disorders is recommended. Knowledge of personality disorders may allow psychological support that would improve the treatment options for dry eye syndrome.

Unusual intraconal localization of orbital giant cell angiofibroma.

PubMed

Ekin, Meryem Altin; Ugurlu, Seyda Karadeniz; Cakalagaoglu, Fulya

2018-01-01

Giant cell angiofibroma (GCA) is a recently reported rare soft-tissue tumor that can develop in various sites including orbit. Orbital GCAs were mainly located in the eyelid or extraconal regions such as lacrimal gland and conjunctiva. We report an atypical case of a GCA arising in the intraconal area of the orbit in a 65-year-old male patient. The tumor was excised in total by lateral orbitotomy. Histological and immunohistochemical features were consistent with the diagnosis of GCA. No recurrence was observed during the follow-up of over 2 years. GCA is a rare tumor that should be considered in the differential diagnosis of intraconal orbital tumors. Complete surgical removal is the current optimal treatment option.

[Raise awareness of IgG4 relative ocular disease].

PubMed

Wei, Shihui; Li, Hongyang

2015-12-01

Purpose IgG4-related ocular disease is a chronic systemic disease with lymphocyte abnormal. The lacrimal glands, extraocular muscles and infraorbital nerve were often involved which was often the first symptom of systemic disease. While ophthalmologists did not know this disease well. They usually misdiagnosed it as idiopathic inflammatory pseudotumor, thyroid-associated ophthalmopathy etc, which resulted in delayed treatments. Here pathogenesis, clinical features and treatment methods of IgG4-relative ocular disease were described in order to improve awareness of this ocular disease, reduce clinical misdiagnosis, improve disease prognosis and standardized treatment. As the incidence of this disease increased in recent years, it is very necessary to improve awareness of the disease for ophthalmologists.

Acquired fistula of the lacrimal sac and laisser-faire approach. Description of the natural history of acquired fistulas between the lacrimal sac and the skin occurring before planned endonasal dacryocystorhinostomy (DCR) and without any treatment of the fistula.

PubMed

Pison, A; Fau, J-L; Racy, E; Fayet, B

2016-10-01

The formation of a fistula between the lacrimal sac and the skin is a classic outcome of resistant lacrimal sac abscesses. There is currently no consensus about treatment in such cases. The goal of this study was to describe the natural history of acquired fistulas between the lacrimal sac and the skin, occurring before planned endonasal dacryocystorhinostomy (DCR) and without any treatment of the fistula. This prospective study was only descriptive and included patients between 1999 and 2012. The patients included were adults with a nasolacrimal duct (NLD) obstruction that was planned to be treated with endonasal DCR. A resistant lacrimal sac abscess appeared a few days before the planned surgery, and fistulized spontaneously despite medical treatment. The surgery was not delayed. The DCR was endoscopic. Nothing was done for the fistula. Its healing was spontaneous. The exclusion criteria were the following: congenital fistulas, post-traumatic and/or iatrogenic fistulas, fistulas which had regressed by the day of the surgery, postoperative follow-up less than 5 months, post-traumatic and/or iatrogenic fistulas, any history of previous DCR or any other lacrimal surgery, children. Twenty adults (25 cases) were included in the analysis. Mean age was 79 years old (from 41 to 90). The mean follow-up was 41 months (from 5 to 108 months). The fistula spontaneously disappeared in all cases, less than one month after it had appeared and in a permanent fashion. No unsightly scar developed. Spontaneously acquired fistulas between the lacrimal sac and the skin may occur in the natural course of abscessed acute dacryocystitis. Our study showed spontaneous healing of the fistula post-endoscopic DCR. Fistula excision in fistulous acute dacryocystitis does not seem essential to its healing. The laisser-faire approach appears adequate for aesthetic outcomes as well as for functional outcomes of DCR. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Movement of the lacrimal canalicular wall under intracanalicular pressure changes observed with dacryoendoscopy.

PubMed

Kakizaki, Hirohiko; Takahashi, Yasuhiro; Mito, Hidenori; Nakamura, Yasuhisa

2015-01-01

Movement of the lacrimal canalicular wall has been speculated to occur during blinking. Movement of the common internal ostium has been observed under nasal endoscopy, and pressure changes in the lacrimal canalicular cavity have been observed with a pressure sensor; however, lacrimal canalicular wall movement under pressure changes has not been observed. To examine movement of the lacrimal canalicular wall under intracanalicular pressure changes using dacryoendoscopy. The authors examined 20 obstruction-free lacrimal canaliculi in 10 patients. A dacryoendoscope was inserted, and water was poured into the intracanalicular cavity via the dacryoendoscope's water channel. The water was then poured or suctioned to cause positive or negative pressure changes in the intracanalicular cavity, and movement of the lacrimal canalicular wall was examined. The lacrimal canalicular wall moved flexibly with pressure changes. Under positive pressure, the intracanalicular cavity was dilated; however, it narrowed under negative pressure. The extent of movement was more dramatic in the common canalicular portion than the proximal canalicular portion. Intracanalicular pressure changes cause movement of the lacrimal canalicular wall. There was a consistent relationship between intracanalicular cavity changes and pressure changes, possibly contributing to lacrimal drainage of the canaliculus.

Inaccuracy of diagnosis in a cohort of patients on the waiting list for dacryocystorhinostomy when the diagnosis was made by only syringing the lacrimal system.

PubMed

Beigi, B; Uddin, J M; McMullan, T F W; Linardos, E

2007-01-01

Accurate identification of the factors contributing to epiphora is essential in directing appropriate management and treatment strategies. The authors applied a methodical strategy of assessment for epiphora to patients who were already on the waiting list for dacryocystorhinostomy (DCR). The findings were compared to the original findings. Forty-four eyes of 35 patients listed for DCR were re-examined. All canaliculi were examined using four tests: dye disappearance, Jones 1 (dye retrieval), probing using Bowman probes, and syringing of the nasolacrimal duct (NLD) under local anesthesia. Some patients were examined using an endocanalicular mini-endoscope. Patients with NLD obstruction underwent DCR and those with canalicular and NLD stenosis underwent intubation of the lacrimal system-canaliculus, lacrimal sac, and nasolacrimal duct-using silicone stents. The authors refer to this as canaliculodacryocystoplasty (CDCP). The patients were assessed for symptoms of epiphora at 12 months. Forty-four eyes had been listed for DCR. They had been originally diagnosed, by means of lacrimal syringing, as NLD obstruction (24 eyes) or stenosis (12 eyes), and functional blocks (8 eyes). Four out of the original 44 planned DCR surgeries were performed after re-evaluation. After re-examination, 28 lacrimal systems were found to have canalicular stenosis, 4 NLD stenosis, 4 NLD obstruction, 4 punctal phimosis, 3 ocular surface disease, and 1 patient was asymptomatic. Twenty-eight lacrimal systems underwent CDCP, 4 underwent DCR, 4 had punctoplasty, and 4 had probing alone. Three had treatment for ocular surface disease and one patient required no treatment. After a follow-up of 12 months, 41 (93%) systems had improvement or were free of their Syringing of the lacrimal apparatus may result in a high false positive diagnosis of NLD obstruction. Canalicular pathology is not uncommon in this cohort of patients and may be underdiagnosed.

Topical administration of lacritin is a novel therapy for aqueous-deficient dry eye disease.

PubMed

Vijmasi, Trinka; Chen, Feeling Y T; Balasubbu, Suganthalakshmi; Gallup, Marianne; McKown, Robert L; Laurie, Gordon W; McNamara, Nancy A

2014-07-17

Lacritin is a tear glycoprotein with prosecretory, prosurvival, and mitogenic properties. We examined lacritin levels in the tears of Sjögren's syndrome (SS) patients and explored the therapeutic potential of topical lacritin for the treatment of keratoconjunctivitis sicca. Tears from healthy controls (n = 14) and SS patients (n = 15) were assayed for lacritin using a C-terminal antibody. In a paired-eye study, autoimmune regulator (Aire) knockout (KO) mice (n = 7) were treated three times daily for 21 days with 10 μL of 4 μM lacritin (left eye) or vehicle (PBS) control (right eye). Tear secretion and ocular surface integrity were assessed at baseline and after treatment. Immunohistochemical staining of CD4+ T cells, cytokeratin-10 (K10), and cytokeratin-12 (K12) expression in the cornea and CD4+ T cell infiltration in the lacrimal glands were assessed. Lacritin monomer (421.8 ± 65.3 ng [SS] vs. 655.8 ± 118.9 ng [controls]; P = 0.05) and C-terminal fragment protein (125 ± 34.1 ng [SS] vs. 399.5 ± 84.3 ng [controls]; P = 0.008) per 100 μL of tear eluate were significantly lower in SS patients. In Aire KO mice treated with lacritin, tear secretion increased by 46% (13.0 ± 3.5 mm vs. 8.9 ± 2.9 mm; P = 0.01) and lissamine green staining score significantly decreased relative to baseline (-0.417 ± 0.06 vs. 0.125 ± 0.07; P = 0.02). Expression of K10 but not K12 in the cornea was significantly decreased in lacritin-treated eyes. Focal CD4+ T cell infiltration of the lacrimal glands was significantly reduced on the lacritin-treated side versus the untreated side. Lacritin is significantly reduced in the tears of SS patients. Topically administered lacritin has therapeutic potential for the treatment of aqueous-deficient dry eye disease. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

[Angiolymphoid hyperplasia with eosinophilia with bilateral involvement of the lacrimal glands].

PubMed

Baráková, Drahomíra; Sâch, Josef; Kuchynka, Pavel; Rêdinová, Magdalena; Kocur, Ivo

2002-05-01

Angiolymphoid hyperplasia with eosinophilia (ALHE) and Kimura's disease are two rarely occurring disorders very similar to each other; however, they are individual nosological entities. For a long time they were considered as a single disease due to the frequency of similar characteristics. The majority of authors have recently considered these diseases as two individual entities with some reciprocal specifications, both clinical as well as morphological. We report on the case of a 76-year old male white European who had suffered for more than six years from subcutaneous tumour formations in different parts of the body. Eyelid oedema on the right side with palpable resistance under the upper temporal edge of the orbit initially occurred five years after the first symptoms of the disease. A similar finding occurred on the left side after eight months. The tumours on both sides were surgically removed and sent for histological analysis. A unilateral recurrence of the finding appeared after one year, followed by surgical intervention and histological examination. Tumour infiltrate in the first two orbita excisions was topically related to lacrimal gland structures; these structures were not found in the third excision. The case was histologically diagnosed as ALHE despite some similar characteristics with Kimura's disease. The diagnosis of ALHE was histologically supported, especially by the absence of lymphatic follicle formations and fibrotisation in the infiltrate, and the identification of the appearance of epitheloid up to histiocytoid of proliferating endothelium, which forms small lumens. The diagnosis of ALHE was additionally supported by the fact that the incidence of Kimura's disease in white Europeans is very rare. According to our findings, both entities overlap one another, even in some characteristics considered to be distinguishing. The question arises, therefore, whether the strict separation of these nosological entities can indeed be determined with one hundred percent accuracy.

Oral involvement in patients with primary Sjögren's syndrome. Multidisciplinary care by dentists and rheumatologists.

PubMed

López-Pintor, Rosa María; Fernández Castro, Mónica; Hernández, Gonzalo

2015-01-01

Primary Sjögren's syndrome is a chronic systemic autoimmune disease that causes destruction of lacrimal and salivary glands. The most common and earliest symptoms are oral and ocular dryness. Dry mouth makes talking difficult, tasting and chewing properly, impairing quality of life of these patients. The most common oral signs and symptoms are hyposialia with or without xerostomia, tooth decay, fungal infections, traumatic oral lesions, dysphagia, dysgeusia, and inflammation of salivary glands. There are different therapeutic strategies, depending on the severity of each case, and the increase in the amount of saliva, to reduce the number of cavities and oral infections. It is particularly important to establish a close relationship between the dentist and the rheumatologist in order to make an early and correct diagnosis, promoting appropriate dietary and hygiene measures, as well as to treat and prevent potential oral complications. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Surgical treatment of dry eye syndrome: conjunctival graft of the minor salivary gland.

PubMed

Güerrissi, Jorge Orlando; Belmonte, Javier

2004-01-01

Despite the availability of efficient tear substitutes, many patients with dry eye syndrome experience severe corneal injuries and a subsequent loss of vision. Surgical techniques using mayor salivary glands to provide a substitute for tears have been reported; with this technique the drainage of saliva goes into the conjunctival fornix, permitting corneal and conjunctival humidification. The authors describe a new surgical approach in which minor salivary glands are autotransplanted into the conjunctival fornix by means of a graft of the intraoral mucosa-transporting salivary glands. This approach was used in a 56-year-old woman with a 2-year history of refractory and pharmacologically untreatable dry eye syndrome caused by Sjögren's syndrome. The right eye had more severe corneal and conjunctival lesions than did the contralateral one, so the treatment was planned in the right eye only. A weekly follow-up during the first 6 months confirmed the significant improvement of dry eye symptoms in the surgically treated eye. Three months after surgery, a biopsy was performed in the minor salivary gland graft, and the histologic findings revealed the presence of glandular acinus, duct with mucin content, and lymphocyte infiltration. The significant improvement obtained in this patient suggests that the secretion from the grafted salivary minor glands was better in promoting homeostasis of the ocular surface than are artificial tears. This may be explained by: (1) The lacrimal and salivary secretions contain biologically active constituents that may protect from infection and promote normal growth epithelium; (2) The secreted mucin is thought to coat the epithelial surface, reducing the high surface tension of the eye wetted by aqueous tears; (3) The thick secretions of the minor gland might act in reducing the evaporation of the underlying tear layer and form a hydrophobic barrier along the lid margin that can retain the lid margin tear string and prevent its flow onto the skin. Minor gland salivary autotransplant is a new surgical technique with effectiveness demonstrated in one patient, but the scientific explanation is not clear; additional experience with more cases could confirm the initial success.

Unusual intraconal localization of orbital giant cell angiofibroma

PubMed Central

Ekin, Meryem Altin; Ugurlu, Seyda Karadeniz; Cakalagaoglu, Fulya

2018-01-01

Giant cell angiofibroma (GCA) is a recently reported rare soft-tissue tumor that can develop in various sites including orbit. Orbital GCAs were mainly located in the eyelid or extraconal regions such as lacrimal gland and conjunctiva. We report an atypical case of a GCA arising in the intraconal area of the orbit in a 65-year-old male patient. The tumor was excised in total by lateral orbitotomy. Histological and immunohistochemical features were consistent with the diagnosis of GCA. No recurrence was observed during the follow-up of over 2 years. GCA is a rare tumor that should be considered in the differential diagnosis of intraconal orbital tumors. Complete surgical removal is the current optimal treatment option. PMID:29283151

Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging.

PubMed

Demirci, Emre; Sahin, Onur Erdem; Ocak, Meltem; Akovali, Burak; Nematyazar, Jamal; Kabasakal, Levent

2016-11-01

Ga-PSMA-11 is a novel PET tracer suggested to be used for imaging of advanced prostate cancer. In this study, we aimed to present a detailed biodistribution of Ga-PSMA-11, including physiological and benign variants of prostate-specific membrane antigen (PSMA) imaging. We carried out a retrospective analysis of 40 patients who underwent PSMA PET/computed tomography (CT) imaging and who had no evidence of residual or metastatic disease on the scans. In addition, 16 patients who underwent PSMA PET/CT imaging with any indication other than prostate cancer were included in the study to evaluate physiological uptake in the normal prostate gland. The median, minimum-maximum, and mean standardized uptake value (SUV) values were calculated for visceral organs, bone marrow and lymph nodes, and mucosal areas. Any physiological variants or benign lesions with Ga-PSMA-11 were also noted. Ga-PSMA-11 uptake was noted in the kidneys, parotid and submandibular glands, duodenum, small intestines, spleen, liver, and lacrimal glands, and mucosal uptake in the nasopharynx, vocal cords, pancreas, stomach, mediastinal blood pool, thyroid gland, adrenal gland, rectum, vertebral bone marrow, and testes. Celiac ganglia showed slight Ga-PSMA-11 uptake in 24 of 40 patients without the presence of any other pathologic lymph nodes in abdominal and pelvic areas. Variable uptake of Ga-PSMA-11 was observed in calcified choroid plexus, a thyroid nodule, an adrenal nodule, axillary lymph nodes and celiac ganglia, occasional osteophytes, and gallbladder. The patient group with PSMA PET/CT for indications other than prostate cancer (n=16) showed a slight radiotracer uptake in normal prostate gland (SUVmax: 5.5±1.6, range: 3.5-8.3). This study shows normal distribution pattern, range of SUVs, and physiological variants of Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.

Morphogenesis of the human excretory lacrimal system

PubMed Central

de la Cuadra-Blanco, C; Peces-Peña, M D; Jáñez-Escalada, L; Mérida-Velasco, J R

2006-01-01

The aim of this study was to determine the principal developmental stages in the formation of the excretory lacrimal system in humans and to establish its morphogenetic period. The study was performed using light microscopy on serial sections of 51 human specimens: 33 embryos and 18 fetuses ranging from 8 to 137 mm crown–rump length (CR; 5–16 weeks of development). Three stages were identified in the morphogenesis of the excretory lacrimal system: (1) the formative stage of the lacrimal lamina (Carnegie stages 16–18); (2) the formative stage of the lacrimal cord (Carnegie stages 19–23); and (3) the maturative stage of the excretory lacrimal system, from the 9th week of development onward. A three-dimensional reconstruction of the excretory lacrimal system was performed from serial sections of an embryo at the end of the embryonic period (27 mm CR). PMID:16879594

Measurement of Lacrimal Sac Fossa Using Orbital Computed Tomography.

PubMed

Kang, Dongwan; Park, Jinhwan; Na, Jaehoon; Lee, Hwa; Baek, Sehyun

2017-01-01

To evaluate the clinical usefulness of measuring the lacrimal sac fossa length using orbital computed tomography in normal Koreans. The authors retrospectively evaluated 140 patients (70 males and 70 females) who underwent orbital computed tomography at Guro Hospital and who had no history of orbital disease or orbital trauma. Computed tomography scans of the right orbit, including the proportion of the lacrimal bone and maxillary bone that comprise the lacrimal sac fossa, were evaluated at 3 different axial planes (lower, middle, and upper levels). Additionally, the mid-point thickness and maximum thickness of the maxillary bone were measured. Finally, the authors also evaluated the relationship between nasal bone height and maxillary bone thickness in the lacrimal sac fossa. Maxillary bone thickness in the lacrimal sac fossa was thicker in males than in females at mid-point thickness and maximum thickness (P < 0.05). However, there was no significant difference in the size of the lacrimal sac fossa and the proportion of the maxillary bone between males and females.In comparisons between maxillary cross-sections, bone thickness was greater toward the upper level of the lacrimal sac fossa (P = 0.008), and the proportion of the maxillary bone was also greater (P = 0.006).Aging had a significant positive correlation with maxillary bone thickness at all 3 axial planes (P < 0.05), but there was no relationship between age and maxillary bone proportion. Nasal bone height and maxillary bone thickness were also not significantly related. In comprising the lacrimal sac fossa, the maxillary bone accounted for a bigger proportion than the lacrimal bone. Male maxillary bone thickness was greater than female thickness. The authors also observed that maxillary bone thickness increased toward the upper areas of the lacrimal sac fossa and with increasing subject age. Understanding the form and variation of a normal lacrimal sac fossa is helpful for preparing for a successful osteotomy with endoscopic dacryocystorhinostomy.

Efficacy of a new topical cationic emulsion of cyclosporine A on dry eye clinical signs in an experimental mouse model of dry eye.

PubMed

Daull, Philippe; Feraille, Laurence; Barabino, Stefano; Cimbolini, Nicolas; Antonelli, Sophie; Mauro, Virgine; Garrigue, Jean-Sébastien

2016-12-01

Dry eye disease (DED) is a complex, multifactorial pathology characterized by corneal epithelium lesions and inflammation. The aim of the present study was to evaluate the efficacy of a cationic emulsion of cyclosporine A (CsA) in a mouse model that mimics severe dry eye. Eight to 12-week-old female C57BL/6N mice with tail patches of scopolamine were housed in controlled environment chambers to induce dry eye. At day three, following dry eye confirmation by corneal fluorescein staining (CFS, score 0-15) and phenol red thread (PRT) lacrimation test, the mice (n = 10/gp) were either treated 3 times a day in both eyes with drug-free cationic emulsion, a 0.1% CsA cationic emulsion, or 1% methylprednisolone (positive control), or non-treated. Aqueous tear production and CFS scores were evaluated at baseline and throughout the treatment period. The lacrimation test confirmed the scopolamine-induced decrease in aqueous production by the lacrimal gland. A reduction of 59% in induced-CFS was observed following topical treatment with 0.1% CsA. The beneficial effect of the cationic emulsion vehicle itself on keratitis was also clearly evidenced by its better performance over 1% methylprednisolone, -36%, vs. -28% on the CFS scores, respectively. This study indicates that the cationic emulsion of CsA (0.1%) was a very effective formulation for the management of corneal epithelium lesions in a severe DED mouse model. In addition, it performed better than a potent glucocorticosteroid (1% methylprednisolone). This cationic emulsion of CsA (0.1%), combining CsA and a tear film oriented therapy (TFOT), i.e. with vehicle properties that mechanically stabilize the tear film, represents a promising new treatment strategy for the management of the signs of dry eye. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

DEBS – a unification theory for dry eye and blepharitis

PubMed Central

Rynerson, James M; Perry, Henry D

2016-01-01

For many years, blepharitis and dry eye disease have been thought to be two distinct diseases, and evaporative dry eye distinct from aqueous insufficiency. In this treatise, we propose a new way of looking at dry eye, both evaporative and insufficiency, as the natural sequelae of decades of chronic blepharitis. Dry eye is simply the late form and late manifestation of one disease, blepharitis. We suggest the use of a new term in describing this one chronic disease, namely dry eye blepharitis syndrome (DEBS). Bacteria colonize the lid margin within a structure known as a biofilm. The biofilm allows for population densities that initiate quorum-sensing gene activation. These newly activated gene products consist of inflammatory virulence factors, such as exotoxins, cytolytic toxins, and super-antigens, which are then present for the rest of the patient’s life. The biofilm never goes away; it only thickens with age, producing increasing quantities of bacterial virulence factors, and thus, increasing inflammation. These virulence factors are likely the culprits that first cause follicular inflammation, then meibomian gland dysfunction, aqueous insufficiency, and finally, after many decades, lid destruction. We suggest that there are four stages of DEBS which correlate with the clinical manifestations of folliculitis, meibomitis, lacrimalitis, and finally lid structure damage evidenced by entropion, ectropion, and floppy eyelid syndrome. When one fully understands the structure and location of the glands within the lid, it becomes easy to understand this staged disease process. The longer a gland can resist the relentless encroachment of the invading biofilm, the longer it can maintain normal function. The stages depend purely on anatomy and years of biofilm presence. Dry eye now becomes a very easy disease to understand. We feel that dry eye should be treated and prevented by early and routine biofilm removal through electromechanical lid margin debridement. PMID:28003734

Making the diagnosis of Sjögren's syndrome in patients with dry eye.

PubMed

Beckman, Kenneth A; Luchs, Jodi; Milner, Mark S

2016-01-01

Sjögren's syndrome (SS) is a chronic and progressive systemic autoimmune disease that often presents initially with symptoms of dry eye and dry mouth. Symptoms are often nonspecific and develop gradually, making diagnosis difficult. Patients with dry eye complaints warrant a step-wise evaluation for possible SS. Initial evaluation requires establishment of a dry eye diagnosis using a combination of patient questionnaires and objective ocular tests, including inflammatory biomarker testing. Additional work-up using the Schirmer test and tear film break-up time can differentiate between aqueous-deficient dry eye (ADDE) and evaporative dry eye. The presence of ADDE should trigger further work-up to differentiate between SS-ADDE and non-SS-ADDE. There are numerous non-ocular manifestations of SS, and monitoring for SS-related comorbid findings can aid in diagnosis, ideally in collaboration with a rheumatologist. The clinical work-up of SS can involve a variety of tests, including tear function tests, serological tests for autoantibody biomarkers, minor salivary gland and lacrimal gland biopsies. Examination of classic SS biomarkers (SS-A/Ro, SS-B/La, antinuclear antibody, and rheumatoid factor) is a convenient and non-invasive way of evaluating patients for the presence of SS, even years prior to confirmed diagnosis, although not all SS patients will test positive, particularly those with early disease. Recently, newer biomarkers have been identified, including autoantibodies to salivary gland protein-1, parotid secretory protein, and carbonic anhydrase VI, and may allow for earlier diagnosis of SS. A diagnostic test kit is commercially available (Sjö(®)), incorporating these new biomarkers along with the classic autoantibodies. This advanced test has been shown to identify SS patients who previously tested negative against traditional biomarkers only. All patients with clinically significant ADDE should be considered for serological assessment for SS, given the availability of new serological diagnostic tests and the potentially serious consequences of missing the diagnosis.

Making the diagnosis of Sjögren’s syndrome in patients with dry eye

PubMed Central

Beckman, Kenneth A; Luchs, Jodi; Milner, Mark S

2016-01-01

Sjögren’s syndrome (SS) is a chronic and progressive systemic autoimmune disease that often presents initially with symptoms of dry eye and dry mouth. Symptoms are often nonspecific and develop gradually, making diagnosis difficult. Patients with dry eye complaints warrant a step-wise evaluation for possible SS. Initial evaluation requires establishment of a dry eye diagnosis using a combination of patient questionnaires and objective ocular tests, including inflammatory biomarker testing. Additional work-up using the Schirmer test and tear film break-up time can differentiate between aqueous-deficient dry eye (ADDE) and evaporative dry eye. The presence of ADDE should trigger further work-up to differentiate between SS-ADDE and non-SS-ADDE. There are numerous non-ocular manifestations of SS, and monitoring for SS-related comorbid findings can aid in diagnosis, ideally in collaboration with a rheumatologist. The clinical work-up of SS can involve a variety of tests, including tear function tests, serological tests for autoantibody biomarkers, minor salivary gland and lacrimal gland biopsies. Examination of classic SS biomarkers (SS-A/Ro, SS-B/La, antinuclear antibody, and rheumatoid factor) is a convenient and non-invasive way of evaluating patients for the presence of SS, even years prior to confirmed diagnosis, although not all SS patients will test positive, particularly those with early disease. Recently, newer biomarkers have been identified, including autoantibodies to salivary gland protein-1, parotid secretory protein, and carbonic anhydrase VI, and may allow for earlier diagnosis of SS. A diagnostic test kit is commercially available (Sjö®), incorporating these new biomarkers along with the classic autoantibodies. This advanced test has been shown to identify SS patients who previously tested negative against traditional biomarkers only. All patients with clinically significant ADDE should be considered for serological assessment for SS, given the availability of new serological diagnostic tests and the potentially serious consequences of missing the diagnosis. PMID:26766898

Minimally invasive medial maxillectomy and the position of nasolacrimal duct: the CT study.

PubMed

Sieskiewicz, Andrzej; Buczko, Krzysztof; Janica, Jacek; Lukasiewicz, Adam; Lebkowska, Urszula; Piszczatowski, Bartosz; Olszewska, Ewa

2017-03-01

Several minimally invasive modifications of endoscopic medial maxillectomy have been proposed recently, with the least traumatic techniques utilizing the lacrimal recess as a route to enter the sinus. The aim of the study was to analyze the anatomy of medial maxillary wall in the region of nasolacrimal canal and, thus, to determine the capability of performing minimally invasive approach to the maxillary sinus leading through the lacrimal recess. The course of nasolacrimal canal and the distance between the anterior maxillary wall and the nasolacrimal canal (the width of lacrimal recess) were evaluated in 125 randomly selected computed tomography (CT) head examinations. The proportion of cases with unfavorable anatomical conditions (lacrimal recess too narrow to accept a 4 mm optic) to perform minimally invasive middle maxillectomy was assessed. The width of lacrimal recess, measured at the level of the inferior turbinate attachment, varied between 0 and 15.2 mm and was related to slanted course of nasolacrimal canal. The more perpendicular the axis of the canal to the nasal flor, the narrower the lacrimal recess. In about 16% of cases, lacrimal recess width was less than 4 mm and in 14.4% it was missing. The endoscopic approach to maxillary sinus leading through lacrimal recess is possible in about 70% of patients. In the remaining group of patients when the lacrimal recess is too narrow, this type of approach may be difficult to perform without damaging the piriform aperture rim or bony framework of nasolacrimal duct, or it may be impracticable when lacrimal recess is missing.

Advances in the treatment of ocular dryness associated with Sjögren׳s syndrome.

PubMed

Ciurtin, Coziana; Ostas, Anca; Cojocaru, Viorica M; Walsh, Stephen B; Isenberg, David A

2015-12-01

Sjögren´s syndrome (SS) is an autoimmune rheumatic disease that is characterised by decreased exocrine gland function and frequent ocular symptoms associated with eye dryness. Significantly, dry eyes can lead to corneal abrasions, infection, ulceration, chronic scarring and, in severe cases, perforation. The available conventional therapies have limited efficacy and there are no biologic therapies licensed for use in SS patients. A literature search of PubMed (MEDLINE) and EMBASE electronic data bases was performed covering the period from January 1994 to September 2014. Evidence was graded in categories I-IV and a treatment algorithm, comprising first line, second line and rescue therapies for ocular dryness associated with SS was proposed. It is based on the current evidence of efficacy of different therapies and explores their link with the pathogenesis of ocular dryness associated with SS. Recent developments in the understanding of the pathogenesis of SS provided evidence that the ocular dryness is associated with pathologic infiltration and dysfunction of the lacrimal glands and changes in the tear composition, together with abnormalities involving the neurosecreting circuits. There is good evidence for the efficacy of topical artificial tears, antiinflammatories and Cyclosporine, and oral Pilocarpine and Cevimeline in controlling the symptoms of ocular dryness associated with SS. Conventional DMARDs are not particularly effective in addressing the symptoms of ocular dryness associated with SS, despite being commonly prescribed for other SS manifestations. Emerging evidence suggests that B cell and co-stimulatory targeted therapy may play a role in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

On the Lipid Composition of Human Meibum and Tears: Comparative Analysis of Nonpolar Lipids

PubMed Central

Butovich, Igor A.

2009-01-01

PURPOSE To qualitatively compare the nonpolar lipids present in meibomian gland (MG) secretions (samples T1) with aqueous tears (AT) collected from the lower tear menisci of healthy, non-dry eye volunteers using either glass microcapillaries (samples T2) or Schirmer test strips (samples T3). METHODS Samples T1 to T3 were analyzed with the use of high-pressure liquid chromatography/positive ion mode atmospheric pressure chemical ionization mass spectrometry. Where possible, the unknown lipids were compared with known standards. RESULTS Samples T1 had the simplest lipid composition among all the tested specimens. Samples T2 and T3 were similar to each other but were noticeably different from samples T1. In addition to all the compounds detected in samples T1, lower molecular weight wax esters and other compounds were found in samples T2 and T3. No appreciable amounts of fatty acid amides (e.g., oleamide), ceramides, or monoacyl glycerols were routinely detected. The occasionally observed minor signals of oleamide (m/z 282) in samples T3 were attributed to the contamination of the samples with common plasticizers routinely found in plastic ware extractives and organic solvents. CONCLUSIONS The MG is a prominent source of lipids for the tear film. However, it would have been a mistake to exclude from consideration other likely sources of lipids such as conjunctiva, cornea, and tears produced by the lacrimal glands. These data showed that lipids in AT are more complex than MG secretions, which necessitates more cautious interpretation of the functions of the latter in the tear film. PMID:18487374

On the lipid composition of human meibum and tears: comparative analysis of nonpolar lipids.

PubMed

Butovich, Igor A

2008-09-01

To qualitatively compare the nonpolar lipids present in meibomian gland (MG) secretions (samples T1) with aqueous tears (AT) collected from the lower tear menisci of healthy, non-dry eye volunteers using either glass microcapillaries (samples T2) or Schirmer test strips (samples T3). Samples T1 to T3 were analyzed with the use of high-pressure liquid chromatography/positive ion mode atmospheric pressure chemical ionization mass spectrometry. Where possible, the unknown lipids were compared with known standards. Samples T1 had the simplest lipid composition among all the tested specimens. Samples T2 and T3 were similar to each other but were noticeably different from samples T1. In addition to all the compounds detected in samples T1, lower molecular weight wax esters and other compounds were found in samples T2 and T3. No appreciable amounts of fatty acid amides (e.g., oleamide), ceramides, or monoacyl glycerols were routinely detected. The occasionally observed minor signals of oleamide (m/z 282) in samples T3 were attributed to the contamination of the samples with common plasticizers routinely found in plastic ware extractives and organic solvents. The MG is a prominent source of lipids for the tear film. However, it would have been a mistake to exclude from consideration other likely sources of lipids such as conjunctiva, cornea, and tears produced by the lacrimal glands. These data showed that lipids in AT are more complex than MG secretions, which necessitates more cautious interpretation of the functions of the latter in the tear film.

Ultrasound parameters of normal lacrimal sac and chronic dacryocystitis.

PubMed

Machado, Marco Antonio de Campos; Silva, João Amaro Ferrari; Garcia, Eduardo Alonso; Allemann, Norma

2017-06-01

To compared the ultrasound findings of the lacrimal sac between subjects with normal lacrimal systems those with chronic dacryocystitis. A retrospective study of 10 subjects with a normal lacrimal system (Group 1) and 10 with chronic dacryocystitis (Group 2) diagnosed according to B-mode ultrasound with a 10-MHz transducer and the direct-contact technique (AVISO, Quantel Medical) for lacrimal sac assessment. We analyzed the dimensions, features, and content of the sacs. Characteristics of the population: female: 6, Group 1; 8, Group 2; mean age 48.4 years (SD=19.9; range, 22-80 years), Group 1; 50.5 years (SD=15.5; range, 25-75 years), Group 2. The dimensions of the lacrimal sac were as follows: anteroposterior 1.86 and 10.99 mm in Groups 1 and 2, respectively, p<0.0001; vertical 9.79 and 14.13 mm in Groups 1 and 2, respectively, p=0.049. Qualitative evaluation of the lacrimal sac contents showed hypoechogenic content in Group 1 (10, 100%) and hyperechogenic punctiform content in Group 2 (10, 100%) with partial filling in seven cases (70%). Ultrasonography can differentiate normal lacrimal sacs from sacs compromised by chronic dacryocystitis, thus being useful as an adjunct to clinical examination and surgical planning.

miR-24-3p Suppresses Malignant Behavior of Lacrimal Adenoid Cystic Carcinoma by Targeting PRKCH to Regulate p53/p21 Pathway.

PubMed

Zhang, Ming-Xue; Zhang, Jie; Zhang, Hong; Tang, Hua

2016-01-01

MicroRNA (miRNA) may function as an oncogene or a tumor suppressor in tumorigenesis. However, the mechanism of miRNAs in adenoid cystic carcinoma (ACC) is unclear. Here, we provide evidence that miR-24-3p was downreglated and functions as a tumor suppressor in human lacrimal adenoid cystic carcinoma by suppressing proliferation and migration/invasion while promoting apoptosis. miR-24-3p down-regulated protein kinase C eta (PRKCH) by binding to its untranslated region (3'UTR). PRKCH increased the of the cell growth and migration/invasion in ACC cells and suppressed the expression of p53 and p21 in both mRNA and protein level. The overexpression of miR-24-3p decreased its malignant phenotype. Ectopic expression of PRKCH counteracted the suppression of malignancy induced by miR-24-3p, as well as ectopic expression of miR-24-3p rescued the suppression of PRKCH in the p53/p21 pathway. These results suggest that miR-24-3p promotes the p53/p21 pathway by down-regulating PRKCH expression in lacrimal adenoid cystic carcinoma cells.

Effects of Quercetin in a Mouse Model of Experimental Dry Eye.

PubMed

Oh, Ha Na; Kim, Chae Eun; Lee, Ji Hyun; Yang, Jae Wook

2015-09-01

To evaluate the effect of treatment with quercetin in a mouse model of dry eye. 0.5% quercetin eye drops were prepared and an experimental dry eye model was induced in NOD.B10.H2(b) mice through desiccation stress. The mice were divided into 3 groups according to the treatment regimen: the DS 10D group (desiccation stress for 10 days), the phosphate buffered saline (PBS) group, and the quercetin group. Tear volumes and corneal irregularity scores were measured at 3, 5, 7, and 10 days after treatment. Hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemistry were performed at the end of the experiment. The quercetin group had increased tear volumes (0.2 ± 0.03 μm, P < 0.05) and decreased corneal irregularity scores (0.7 ± 0.6, P < 0.05) compared with those of the PBS group. On histological examination, the quercetin group exhibited restored smooth corneal surfaces without detaching corneal epithelial cells and had significantly increased goblet cell density (13.8 ± 0.8 cells/0.1 mm², P < 0.05) compared with the PBS group. The quercetin group also exhibited significant declines of MMP-2 (5.1-fold of control, P < 0.01), MMP-9 (2.5-fold of control, P < 0.01), ICAM-1 (2.2-fold of control, P < 0.01), and VCAM-1 (2.3-fold of control, P < 0.01) levels in the lacrimal gland than did the PBS group. Topical application of quercetin can help to improve ocular surface disorders of dry eye not only by decreasing the corneal surface irregularity but also by increasing the tear volume and goblet cell density. Moreover, quercetin has the potential for use in eye drops as a treatment for dry eye disease with antiinflammatory effects on the lacrimal functional unit.

Endoscopic endonasal dacryocystorhinostomy combined with canaliculus repair for the management of dacryocystitis with canalicular obstruction.

PubMed

Tu, Yunhai; Qian, Zhenbin; Zhang, Jiao; Wu, Wencan; Xiao, Tianlin

2015-01-01

Purpose. The aim of this study is to propose a simple and efficient combination surgery for the management of dacryocystitis with canalicular obstruction. Methods. A retrospective noncomparative case series of dacryocystitis with canalicular obstruction has been studied. Twelve patients with dacryocystitis and canalicular obstruction underwent a conventional endoscopic endonasal dacryocystorhinostomy (EE-DCR) combined with a modified canalicular repair. Postoperative observations included slit lamp, fluorescein dye disappearance test, lacrimal syringing, lacrimal endoscopy, and nasal endoscopy. Results. After 6-18 months of postoperative follow-up, the symptoms of epiphora and mucopurulent discharge disappeared completely in 10 patients, and occasional or intermittent epiphora remained in 2 patients. All of the twelve patients showed an opened intranasal ostium and normal fluorescein dye disappearance test. Patent bicanalicular irrigation was achieved in 9 patients. One patient had a partial and the other two had a complete reobstruction by lacrimal irrigation to their repaired lower canaliculus; however, all of them had a patent lacrimal irrigation to upper canaliculus. The functional success rate for the combination surgery is 83% (10/12), and anatomical success rate is 75% (9/12). Conclusion. EE-DCR combined with modified canalicular repair is a simple and efficient method for the management of dacryocystitis with canalicular obstruction.

Membrane interactions between secretion granules and plasmalemma in three exocrine glands

PubMed Central

Tanaka, Y; De Camilli, P; Meldolesi, J

1980-01-01

Three types of membrane interactions were studied in three exocrine systems (the acinar cells of the rat parotid, rat lacrimal gland, and guinea pig pancrease) by freeze- fracture and thin-section electron microscopy: exocytosis, induced in vivo by specific pharmacological stimulations; the mutual apposition of secretory granule membranes in the intact cell; membrane appositions induced in vitro by centrifugation of the isolated granules. In all three glandular cells, the distribution of intramembrane particles (IMP) on the fracture faces of the luminal plasmagranule membrane particles (IMP) on the fracture faces of the lumenal plasmalemma appeared random before stimulation. However, after injection of secretagogues, IMP were rapidly clearly from the areas of granule- plasmalemma apposition in the parotid cells and, especially, in lacrimocytes. In the latter, the cleared areas appeared as large bulges toward the lumen, whereas in the parotid they were less pronounced. Exocytotic openings were usually large and the fracture faces of their rims were covered with IMP. In contrast, in stimulated pancreatic acinar cells, the IMP distribution remained apparently random after stimulation. Exocytoses were established through the formation of narrown necks, and no images which might correspond to early stages of membrane fusion were revealed. Within the cytoplasm of parotid and lacrimal cells (but not in the pancreas), both at rest and after stimulation, secretion granules were often closely apposed by means of flat, circular areas, also devoid of IMP. In thin sections, the images corresponding to IMP-free areas were close granule-granule and granule-plasmalemma appositions, sometimes with focal merging of the membrane outer layers to yield pentalaminar structures. Isolated secretion granules were forced together in vitro by centrifugation. Under these conditions, increasing the centrifugal force from 1,600 to 50,000 g for 10 min resulted in a progressive, statistically significant increase of the frequency of IMP-free flat appositions between parotid granules. In contrast, no such areas were seen between freeze-fractured pancreatic granules, although some focal pentalaminar appositions appeared in section after centrifugation at 50 and 100,000 g for 10 min. On the basis of the observation that, in secretory cells, IMP clearing always develops in deformed membrane areas (bulges, depressions, flat areas), it is suggested that it might result from the forced mechanical apposition of the interacting membranes. This might be a preliminary process not sufficient to initiate fusion. In the pancreas, IMP clearing could occur over surface areas too small to be detected. In stimulated parotid and lacrimal glands they were exceptional. These structures were either attached at the sites of continuity between granule and plasma membranes, or free in the acinar lumen, with a preferential location within exocytotic pockets or in their proximity. Experiments designed to investigate the nature of these blisters and vesicles revealed that they probably arise artifactually during glutaraldehyde fixation. In fact, (a) they were large and numerous in poorly fixed samples but were never observed in thin sections of specimens fixed in one step with glutaraldehyde and OsO(4); and (b) no increase in concentration of phospholipids was observed in the parotid saliva and pancreatic juice after stimulation of protein discharge, as was to be expected if release of membrane material were occurring after exocytosis. PMID:7380885

[Papilloma of the lacrimal sac].

PubMed

Burduk, Paweł K; Seredyka-Burduk, Małgorzata; Kaźmierczak, Wojciech; Dalke, Krzysztof; Marszałek, Andrzej

2013-01-01

The benign lesions of the lacrimal sac are very rare. The most typical epithelial tumor is squamous papilloma. This tumors often present with symptoms of dacryostenosis and dacriocystitis. Human papillomavirus (HPV) infection is known to be causative agent in the development of epithelial tumor. Lacrimal sac tumors could transform to malignant neoplasms, especially if they are developed of coexisting HPV infection. We present a patient with a squamous papilloma of the lacrimal sac and discussed the method of treatment. The patient was suffered from epiphora and recurrent dacriocystitis. An endoscopic surgery with dacriocystorhinostomy and local resection of the tumor could be an effective method of choice. The usage of a shaver for wide removal of the lacrimal sac wall is recommended to prevent local recurrence. The histopathology examination showed squamous papilloma. The patient is free of the disease over 8 months of follow up. Primary lacrimal sac papilloma require long term follow up for recurrence or malignant transformation. HPV infection could be associated with the development of lacrimal sac papillomas. Copyright © 2012 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Potential for daily supplementation of n-3 fatty acids to reverse symptoms of dry eye in mice.

PubMed

Harauma, Akiko; Saito, Junpei; Watanabe, Yoshitake; Moriguchi, Toru

2014-06-01

The purpose of this study was to determine the change in tear volume, as a predominant symptom of dry eye syndrome, in dietary n-3 fatty acid deficient mice compared with n-3 fatty acid adequate mice. The tear volume in n-3 fatty acid deficient mice was significantly lower than that in n-3 fatty acid adequate mice. In addition, the concentration of n-3 fatty acid in the lacrimal and meibomian glands, which affects the production of tears, was markedly decreased compared with n-3 fatty acid adequate mice. However, the tear volume recovered almost completely after one week of continuous administration of fish oil containing EPA and DHA in n-3 fatty acid deficient mice. Also, the concentration of DHA in the meibomian gland of n-3 fatty acid deficient group recovered to approximately 80% more than that of n-3 fatty acid adequate group. These results suggested that dietary n-3 fatty acids deficiency showed reversible dry eye syndrome, and that n-3 fatty acids have an important role in the production of tears. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Endonasal Dacryocystorhinostomy (DCR) with Transcanalicular Endoillumination (TCE) of the Saccus Lacrimalis].

PubMed

Hefner, J; Klask, J; Gerding, H

2016-04-01

Endonasal dacryocystorhinostomy (DCR) has been established as a standard procedure of lacrimal surgery, since it causes much less tissue damage than ab externo procedures. Diffiulties in visualization of the target area has been a limitation to the transnasal approach. An improvement of the classical endonasal DCR was achieved by the introduction of a transcanalicular endoillumination (TCE) of the lacrimal sac using a 23-Gauge vitreoretinal light probe, which can easily be intubated into the cannaliculi and advanced into the the lacrimal sac. Illumination of the lacrimal sac guides the endonasal approach and facilitates the creation of a lacrimal bypass. In our standard procedure a bicanalicular silicone intubation through the osteotomy is finally placed. Due to the introduction of TCE of the lacrimal sac, the surgical procedure of endonasal DCR became less traumatic and needed a significantly reduced operating time. Georg Thieme Verlag KG Stuttgart · New York.

Studies of an Androgen-Binding Protein Knockout Corroborate a Role for Salivary ABP in Mouse Communication

PubMed Central

Chung, Amanda G.; Belone, Phillip M.; Bímová, Barbora Vošlajerová; Karn, Robert C.; Laukaitis, Christina M.

2017-01-01

The house mouse Androgen-binding protein (Abp) gene family is comprised of 64 paralogs, 30 Abpa and 34 Abpbg, encoding the alpha (ABPA) and beta-gamma (ABPBG) protein subunits that are disulfide-bridged to form dimers in secretions. Only 14 Abp genes are expressed in distinct patterns in the lacrimal (11) and submandibular glands (3). We created a knockout mouse line lacking two of the three genes expressed in submandibular glands, Abpa27 and Abpbg27, by replacing them with the neomycin resistance gene. The knockout genotype (−/−) showed no Abpa27 or Abpbg27 transcripts in submandibular gland complementary DNA (cDNA) libraries and there was a concomitant lack of protein expression of ABPA27 and ABPBG27 in the −/− genotype saliva, shown by elimination of these two proteins from the saliva proteome and the loss of cross-reactive material in the acinar cells of the submandibular glands. We also observed a decrease in BG26 protein in the −/− animals, suggesting monomer instability. Overall, we observed no major phenotypic changes in the −/− genotype, compared with their +/+ and +/− siblings raised in a laboratory setting, including normal growth curves, tissue histology, fecundity, and longevity. The only difference is that male and female C57BL/6 mice preferred saliva of the opposite sex containing ABP statistically significantly more than saliva of the opposite sex without ABP in a Y-maze test. These results show for the first time that mice can sense the presence of ABP between saliva targets with and without ABPs, and that they spend more time investigating the target containing ABP. PMID:28159752

Studies of an Androgen-Binding Protein Knockout Corroborate a Role for Salivary ABP in Mouse Communication.

PubMed

Chung, Amanda G; Belone, Phillip M; Bímová, Barbora Vošlajerová; Karn, Robert C; Laukaitis, Christina M

2017-04-01

The house mouse Androgen-binding protein ( Abp ) gene family is comprised of 64 paralogs, 30 Abpa and 34 Abpbg , encoding the alpha (ABPA) and beta-gamma (ABPBG) protein subunits that are disulfide-bridged to form dimers in secretions. Only 14 Abp genes are expressed in distinct patterns in the lacrimal (11) and submandibular glands (3). We created a knockout mouse line lacking two of the three genes expressed in submandibular glands, Abpa27 and Abpbg27 , by replacing them with the neomycin resistance gene. The knockout genotype (-/-) showed no Abpa27 or Abpbg27 transcripts in submandibular gland complementary DNA (cDNA) libraries and there was a concomitant lack of protein expression of ABPA27 and ABPBG27 in the -/- genotype saliva, shown by elimination of these two proteins from the saliva proteome and the loss of cross-reactive material in the acinar cells of the submandibular glands. We also observed a decrease in BG26 protein in the -/- animals, suggesting monomer instability. Overall, we observed no major phenotypic changes in the -/- genotype, compared with their +/+ and +/- siblings raised in a laboratory setting, including normal growth curves, tissue histology, fecundity, and longevity. The only difference is that male and female C57BL/6 mice preferred saliva of the opposite sex containing ABP statistically significantly more than saliva of the opposite sex without ABP in a Y-maze test. These results show for the first time that mice can sense the presence of ABP between saliva targets with and without ABPs, and that they spend more time investigating the target containing ABP. Copyright © 2017 by the Genetics Society of America.

Bilateral congenital lacrimal fistulas in an adult as part of ectrodactyly-ectodermal dysplasia-clefting syndrome: A rare anomaly.

PubMed

Ghosh, Debangshu; Saha, Somnath; Basu, Sumit Kumar

2015-10-01

Ectrodactyly-ectodermal dysplasia and clefting syndrome or "Lobster claw" deformity is a rare congenital anomaly that affects tissues of ectodermal and mesodermal origin. Nasolacrimal duct (NLD) obstruction with or without atresia of lacrimal passage is a common finding of such a syndrome. The authors report here even a rarer presentation of the syndrome which manifested as bilateral NLD obstruction and lacrimal fistula along with cleft lip and palate, syndactyly affecting all four limbs, mild mental retardation, otitis media, and sinusitis. Lacrimal duct obstruction and fistula were managed successfully with endoscopic dacryocystorhinostomy (DCR) which is a good alternative to lacrimal probing or open DCR in such a case.

Penetrating maxillary sinus injury caused by a construction nail passing through the orbital cavity.

PubMed

Simsek, Tekin; Demir, Bulent; Yosma, Engin; Keles, Musa K; Abdullayev, Asef

2014-03-01

Because of its anatomic position, the orbit is frequently subject to trauma, leading to functional and cosmetic problems. After blunt trauma, orbital fractures can cause functional problems by trapping the periocular tissues without affecting the anatomic integrity of the globe. In comparison, high-energy penetrating injuries can cause serious consequences such as disrupting the lacrimal drainage system and causing loss of vision. In rare cases, however, penetration of the orbit by a foreign body can result in a treatable injury that causes no functional or cosmetic problems.This article presents a patient in whom a nail penetrated the orbit from the inferomedial margin and reached the maxillary sinus without damaging the globe, extraocular muscles, or lacrimal duct system. Reports of similar injuries are reviewed, focusing on the anatomic structures that might be traumatized, to guide the readers in considering the diagnosis and treatment of such injuries.

[Ocular surface system integrity].

PubMed

Safonova, T N; Pateyuk, L S

2015-01-01

The interplay of different structures belonging to either the anterior segment of the eye or its accessory visual apparatus, which all share common embryological, anatomical, functional, and physiological features, is discussed. Explanation of such terms, as ocular surface, lacrimal functional unit, and ocular surface system, is provided.

Nanocarriers in ocular drug delivery: an update review.

PubMed

Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani Rai; Vyas, S P

2009-01-01

Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.

Feline dry eye syndrome of presumed neurogenic origin: a case report.

PubMed

Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J

2018-01-01

A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. The final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs.

Analysis of novel Sjogren's syndrome autoantibodies in patients with dry eyes.

PubMed

Everett, Sandra; Vishwanath, Sahana; Cavero, Vanessa; Shen, Long; Suresh, Lakshmanan; Malyavantham, Kishore; Lincoff-Cohen, Norah; Ambrus, Julian L

2017-03-07

Dry eye is a common problem in Ophthalmology and may occur for many reasons including Sjogren's syndrome (SS). Recent studies have identified autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6) and anti-parotid secretory protein (PSP), which occur early in the course of SS. The current studies were designed to evaluate how many patients with idiopathic dry eye and no evidence of systemic diseases from a dry eye practice have these autoantibodies. Patients from a dry eye clinic and normal controls were assessed by Schirmer's test for tear flow. Sera were assessed for autoantibodies using ELISA assays. Statistics was performed with Prism 7 software and student's unpaired t test. In this study 60% of the dry eye patients expressed one of these autoantibodies. Only 30% expressed one of the autoantibodies associated with long-standing SS, which are included in the diagnostic criteria for SS, anti-Ro and anti-La. Patients with disease for less than 2 years and mild dry eyes did not express anti-Ro or anti-La, while 25% expressed anti-SP1. Similar observations, with smaller numbers, were made when patients had not only dry eye but also dry mouth. Antibodies to SP1, CA6 and PSP occur in some patients with idiopathic dry eyes. Further studies will be needed to determine how many of these patients go on to develop systemic manifestations of SS. Testing for these autoantibodies may allow early recognition of patients with SS. This will lead to improved management of the patients and the development of new strategies to maintain normal lacrimal and salivary gland function in patients with SS.

Verification of the new grading scale for ocular chronic graft-versus-host disease developed by the German-Austrian-Swiss consensus conference on chronic GVHD.

PubMed

Blecha, Christiane; Wolff, Daniel; Holler, Barbara; Holler, Ernst; Weber, Daniela; Vogt, Regine; Helbig, Horst; Dietrich-Ntoukas, Tina

2016-02-01

The purpose of the study was to validate a recently proposed new grading system for ocular manifestations of chronic graft-versus-host disease (cGVHD). Diagnosis of cGVHD was based on the NIH consensus criteria. In addition, a grading scale was applied, which has been developed by the German-Austrian-Swiss Consensus Conference on Clinical Practice in cGVHD. Sixty-six patients (male n = 46, female n = 20, mean age 48 years) with ocular cGVHD were included. Application of the proposed Consensus Conference grading revealed inflammatory activity in all patients with mild (33 %), moderate (44 %), or severe inflammation (23 %). Clinical scoring by the NIH scoring system showed that 6 % of patients had mild symptoms; 59 % of patients had moderate dry eye symptoms partially affecting activities of daily living, without vision impairment; and 35 % of patients had severe dry eye symptoms significantly affecting daily activities. Clinical characterization and grading by the Consensus Conference grading scale revealed that ocular cGVHD (1) frequently leads to severe ocular surface disease based on impaired function of the lacrimal glands and involvement of cornea, conjunctiva, and lids; (2) is mostly associated with ongoing inflammatory activity; (3) often leads to functional impairment and reduced quality of life; and (4) is associated with an increased risk for severe, sight-threatening complications.

[Traumatic Lacrimal Duct Stenosis: Demographics and Success Rate of Surgical Procedures for Secondary Treatment].

PubMed

Alnawaiseh, M; Böhm, M R R; Rosentreter, A; Wieneke, A C; Wirths, G; Merté, R L; Eter, N; Zumhagen, L

2016-06-01

Traumatic lacrimal duct stenosis can be the result of sharp trauma of the eyelid, indirect trauma or surgery in the nasoorbital region, as well as burns, chemotherapy and radiation of the facial region. The aim of the study is to present the demographics, patient satisfaction, and course of different surgical procedures for secondary treatment of traumatic lacrimal duct stenosis. We retrospectively reviewed the medical records of 50 patients who required surgery for traumatic lacrimal duct stenosis from 2009 to 2011 at the University Eye Hospital in Muenster. The evaluation included the following criteria: age, sex, duration of symptoms, complication rate and the rate of recurrence. We systematically evaluated the medical data and asked the patients about the recent symptoms via telephone questionnaire. 60 eyes of 50 patients were included (18 women; 32 men; age: 51.8 ± 17.1 years); 34 eyes (56.7 %) had already had operations of the lacrimal system. The success rate was 58.1 %. The mean postoperative follow-up was 52.3 ± 10.7 months. In 11 cases (18.3 %), a dakryocystorhinostomy (DCR) was necessary. Traumatic lacrimal stenosis is more common in men, and has a poorer prognosis than lacrimal duct stenosis from other causes. Georg Thieme Verlag KG Stuttgart · New York.

Analysis of orbital malignancies presenting in a tertiary care hospital in Pakistan

PubMed Central

Khan, Asad Aslam; Sarwar, Suhail; Sadiq, Mohammad Ali A; Ahmad, Imran; Tariq, Nayab; Sibghat-ul-Noor

2017-01-01

Objective: To determine the frequencies of various orbital malignancies amongst orbital lesions in patients presenting in a tertiary care hospital in Pakistan. Methods: A retrospective analysis of 666 orbital cases with an established histopathological diagnosis of malignant tumors treated in Mayo Hospital Lahore from 1996 to 2015 (20 years). Results: About 66% of the malignant tumors were primary, 25% secondary, 8% haematopoietic and 1% metastatic. Almost 50% of the cases were children. Retinoblastoma is the commonest tumor (43% overall and 87% among children). Squamous cell carcinoma is the second commonest (15.6% overall and 31% among adults). These are then followed by Adenoid cystic carcinoma of Lacrimal Gland (9%), Lymphoma/Leukaemia (8%) and Rhabdomyosarcoma (6.3%). Conclusion: Frequencies of various orbital malignancies show geographical variation in both paediatric and adult population. PMID:28367175

Primary Mucoepidermoid Carcinoma of the Lacrimal Sac -  a Case Report and Literature Review.

PubMed

Janakiram, T N; Sagar, S; Sharma, S B; Subramaniam, V

Lacrimal sac tumors are very rare and are often missed because patients present with features consistent with chronic dacryocystitis. Squamous cell carcinoma is the common-est lacrimal sac malignancy. Although primary mucoepidermoid carcinomas of the lacrimal sac are rare, they are locally aggressive. Furthermore, their proximity to vital structures and the skull base makes them potentially life-threatening. Multidisciplinary management is required, and wide excision followed by chemoradiation is the recommended treatment. Here, we report a 65-year-old male who presented with watering eyes and a mass in the region of the medial canthus. A dia-gnosis of primary mucoepidermoid carcinoma of the lacrimal sac was made, and the case was managed successfully with radical surgery and reconstruction. The tumor was resected using the extended Lynch-Howarth incision and the resulting defect was reconstructed using a forehead flap. Histopathological examination of the excised specimen revealed mucoepidermoid carcinoma. Immunohistochemical analysis revealed that the speci-men was positive for epithelial growth factor receptor and Ki-67 protein. The patient was referred for post-operative chemoradiation. The literature is reviewed and pathological features, including immunohistochemistry are discussed. Primary mucoepidermoid carcinoma of the lacrimal sac is a rare, locally aggressive tumor that is often mistaken for dacryocystitis. The treatment of choice is radical surgery followed by chemoradiation. lacrimal sac -  mucoepidermoid carcinoma -  epithelial growth factor receptor -  Ki-67 protein.

4A syndrome: ocular surface investigation in an Italian young patient.

PubMed

Aragona, Pasquale; Rania, Laura; Roszkowska, Anna Maria; Puzzolo, Domenico; Micali, Antonio; Pisani, Antonina; Salzano, Giuseppina; Messina, Maria Francesca

2014-12-08

Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal. The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.

In Vivo Test for Chemical Induction of Micronucleated Polychromatic Erythrocytes in Mouse Bone Marrow Cells. Test Article: Dimethylamine-2-2ethyl azide (DMAZ)

DTIC Science & Technology

2008-06-25

Hunched Back Unusual Body Secretions - Nasal Discharge - Lacrimation - Salivation - Bloody Stool - Dianhea Abnormal Behavior - Convulsions...WetGroin - Hunched Back Unusual Body Secretions - Nasal Discharge - Lacrimation - Salivation - Bloody Stool - Diarrhea Abnormal Behavior...Ataxia - Piloerection - WetGrain - Hunched Back Unusual Body Secretions - Nasal Discharge - Lacrimation - Salivation - Bloody Stool

A silastic sheet found during endoscopic transnasal dacryocystorhinostomy for acute dacryocystitis.

PubMed

Choi, Jin Seok; Lee, Jong Hyeok; Paik, Hae Jung

2006-03-01

To report the case of a silastic sheet that was found during an endoscopic transnasal dacryocystorhinostomy for treatment of acute dacryocystitis with necrosis of the lacrimal sac. A thirty-two year old male presented with painful swelling on the nasal side of his left lower lid two weeks prior to visiting this clinic. Fourteen years ago, the patient was involved in a traffic accident and underwent surgery to reconstruct the ethmoidal sinus. Lacrimal sac massage showed a regurgitation of a purulent discharge from the left lower punctum. Therefore, the patient was diagnosed with acute dacryocystitis and an endoscopic transnasal dacryocystostomy was performed the next day. The surgical finding showed severe necrosis around the lacrimal sac and a 20 x 15-mm sized silastic sheet was found crumpled within the purulent discharge. The sheet was removed, the lacrimal sac was irrigated with an antibiotic solution, and a silicone tube was intubated into the lacrimal pathway. After surgery, the painful swelling on the nasal side of left lower lid resolved gradually, and there were no symptomatic complications three months later. We report the first case where a silastic sheet applied during a facial reconstruction had migrated adjacent to the lacrimal sac resulting in severe inflammation.

Diagnostic imaging of the nasolacrimal drainage system. Part I. Radiological anatomy of lacrimal pathways. Physiology of tear secretion and tear outflow.

PubMed

Maliborski, Artur; Różycki, Radosław

2014-04-17

Excessive watering of the eye is a common condition in ophthalmological practice. It may be the result of excessive production of tear fluid or obstruction and insufficiency of efferent tear pathways. The differentiation between obstruction and insufficiency of the lacrimal pathways is still clinically questionable. In the diagnostic process it is necessary to perform clinical tests and additional diagnostic imaging is often needed. Dacryocystography, with or without the extension of the dynamic phase or subtraction option, still remains the criterion standard for diagnostic imaging of the lacrimal obstruction. It may help to clarify the cause and exact place of the obstruction and provide information for further management, especially surgical treatment. Increasingly, new techniques are used in diagnostic imaging of the lacrimal tract, such as computed tomography, magnetic resonance, and isotopic methods. Adequate knowledge of the anatomy and physiology of the lacrimal system and the secretion and outflow of tears is the basis for proper diagnostic imaging. The purpose of this paper is to present the exact anatomy of the lacrimal system, with particular emphasis on the radiological anatomy and the current state of knowledge about the physiology of tear secretion and drainage.

Feline dry eye syndrome of presumed neurogenic origin: a case report

PubMed Central

Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J

2018-01-01

Case summary A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. Relevance and novel information The final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs. PMID:29318025

Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cameron, R.S.; Cameron, P.L.; Castle, J.D.

1986-10-01

A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pImore » and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion.« less

Sjogren's syndrome from the perspective of ophthalmology.

PubMed

Kuklinski, Eric; Asbell, Penny A

2017-09-01

Sjogren's syndrome (SS) is an autoimmune disease affecting the lacrimal glands resulting in dry eye disease (DED). Ophthalmologists may be the first line of detection of Sjogren's syndrome given the frequency of DED in SS and that dry eye is often the presenting symptom. Numerous symptom questionnaires and tests have been developed to help diagnose DED, but as of yet, there is no "gold standard." Minimally invasive objective metrics are needed for a reliable diagnosis of DED. Currently there is no single test to diagnose SS-associated DED. Although there are several approaches to treatment, none are specific for DED in SS, and, generally, several methods need to be tried to find what works best for a specific patient. Treatment for DED continues to be an unmet medical need, especially given that DED in SS is typically on the severe end of the spectrum. Copyright © 2017 Elsevier Inc. All rights reserved.

Thelazia callipaeda infestation in Bangladesh: a case report.

PubMed

Akhanda, A H; Akonjee, A R; Hossain, M M; Rahman, M A; Mishu, F A; Hasan, M F; Akhanda, T H

2013-07-01

A 5 years old girl was admitted to Ophthalmology department of Mymensingh Medical College Hospital, Mymensingh with excessive watering, redness and movement of something in her right eye for last 2 months. She had unaided visual acuity- 6/6, matted eye lashes and mucoid discharge in right eye. Follicles were present on the fornices and lower palpebral conjunctiva of the same eye. On eversion of the right upper lid there were silicon tube like coiled moving structures seen at the lateral part of the upper fornics. Six nematodes were seen in the upper fornics around the duct of lacrimal glands. After removing the nematodes, one specimen was sent to parasitology department of Bangladesh Agriculture University for species identification. They reported that sending specimen is an adult "Thelazia Callipaeda". By the present study, the presence of human ocular T. callipaeda infestation is second reported case in Bangladesh. Ophthalmologists should be aware about parasitic infestation of conjunctiva.

Local and Regional Spread of Primary Conjunctival Squamous Cell Carcinoma.

PubMed

Desai, Shilpa J; Pruzan, Noelle L; Geske, Michael J; Jeng, Bennie H; Bloomer, Michele M; Vagefi, M Reza

2016-04-06

Two cases of biopsy-proven conjunctival squamous cell carcinoma (SCC) that developed local and regional spread are described. The cases involved a 65-year-old woman and a 79-year-old man who were initially treated at outside institutions for SCC of the conjunctiva. The patients did not have a history of immune compromise. The female patient presented with direct extension into the lacrimal gland but deferred recommended exenteration. Despite eventual exenteration, she developed metastasis to a neck node 6 months later, which was treated with radiotherapy. The male patient presented with local recurrence and a parotid node metastasis treated with exenteration, parotidectomy, selective neck dissection, and postoperative radiotherapy. Review of the outside pathology of both cases revealed positive tumor margins at the time of original resection. Local control of conjunctival SCC is of critical importance to reduce the risk of orbital extension and regional spread.

Ocular sarcoidosis masked by positive IgM for toxoplasmosis.

PubMed

Peres, Murilo Bertazzo; Sousa, Jacqueline Martins de; Nascimento, Heloisa

2017-01-01

We report a case of ocular sarcoidosis with positive immunoglobulin (Ig) M and IgG serology for toxoplasmosis. The patient was a young female with red painful eyes, bilateral eyelid edema, and panuveitis with periphlebitis. In laboratory testing, she was IgM and IgG positive for toxoplasmosis and anergic in the tuberculin test. Topical treatment for anterior uveitis and oral antibiotics for toxoplasmosis were started, without improvement. Orbit tomography showed increased lacrimal glands bilaterally, and chest X-ray radiographic findings were consistent with pulmonary sarcoidosis, which supported the presumed ocular sarcoidosis diagnosis. The patient was treated with oral prednisone and methotrexate without antibiotics. She showed clinical and vision improvement without recurrences during the 1-year follow-up. Ocular sarcoidosis is an important differential diagnosis requiring careful anamnesis and ophthalmological examinations. Ancillary tests, such as X-ray radiography, tomography, and clinical and laboratory evaluations may help rule out other causes. Treatment mainly consists of corticosteroids and immunosuppression.

Orbital complications of sinusitis in the aspirin triad syndrome.

PubMed

McFadden, E A; Woodson, B T; Massaro, B M; Toohill, R J

1996-09-01

Orbital complications are uncommon in adult sinusitis. In contrast, the sinusitis of the aspirin triad syndrome is often fulminate, expansive, and recurrent, and complications may be more frequent. Of 81 patients with aspirin triad who were treated surgically, 7 patients (8.6%) had orbital complications, including sinus mucoceles in 3 patients, lacrimal gland extension in 2 patients, inflammatory orbital mass in 1 patient, and proptosis from expansile sinonasal polyposis in 1 patient. All complications manifested within 2 years of prior surgery. Two patients suffered blindness. In a group of 120 consecutively treated sinus surgery patients without aspirin triad syndrome (51 of whom were followed for more than 2 years), no patient manifested nonoperative orbital complications. The results of this study suggest that aspirin triad patients are at significant risk for orbital complications and therefore should have long-term follow-up with aggressive treatment of persistent disease.

Corneal confocal microscopy alterations in Sjögren's syndrome dry eye.

PubMed

Lanza, Michele; Iaccarino, Stefania; Varricchi, Gilda; D'Errico, Tito; Gironi Carnevale, Ugo Antonello; Bifani, Mario

2017-08-01

To evaluate light backscattering (LB) in corneal layers in patients with primary Sjögren's syndrome dry eye (SSDE) utilizing in vivo corneal confocal microscopy (IVCM) and to determine the eventual association with the lacrimal functional test values. A complete ophthalmic evaluation, Schirmer test with and without stimulation, break-up time (BUT) and IVCM were performed on 55 patients affected by SSDE and in an age- and sex-matched cohort of healthy participants (HP). Light backscattering, measures as light reflectivity unit (LRU), detected by IVCM at Bowman's membrane (BM) at 50 μm, at 100 μm and at 200 μm deeper than BM was compared in the two groups. The correlations between LB values and lacrimal function results were evaluated. In patients affected by SSDE, LB was significantly higher (p < 0.001) in each corneal layer examined (+14 ± 6.33 LRU at BM), compared with HP. A good reverse correlation between the light reflectivity measures at BM with Schirmer test with (r = -0.91) and without (r = -0.90) stimulation and BUT (r = -0.88) was found. Correlations were lower in the deeper corneal layers. Even if our results should be confirmed in further studies with a larger population, these findings show that IVCM is a device able to detect alterations in corneal layers in SSDE patients related to the lacrimal function. Light backscattering (LB) could be very useful for clinical diagnosis and management of SSDE. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

A Silastic Sheet found during Endoscopic Transnasal Dacryocystorhinostomy for Acute Dacryocystitis

PubMed Central

Choi, Jin Seok; Paik, Hae Jung

2006-01-01

Purpose To report the case of a silastic sheet that was found during an endoscopic transnasal dacryocystorhinostomy for treatment of acute dacryocystitis with necrosis of the lacrimal sac. Methods A thirty-two year old male presented with painful swelling on the nasal side of his left lower lid two weeks prior to visiting this clinic. Fourteen years ago, the patient was involved in a traffic accident and underwent surgery to reconstruct the ethmoidal sinus. Lacrimal sac massage showed a regurgitation of a purulent discharge from the left lower punctum. Therefore, the patient was diagnosed with acute dacryocystitis and an endoscopic transnasal dacryocystostomy was performed the next day. Results The surgical finding showed severe necrosis around the lacrimal sac and a 20 × 15-mm sized silastic sheet was found crumpled within the purulent discharge. The sheet was removed, the lacrimal sac was irrigated with an antibiotic solution, and a silicone tube was intubated into the lacrimal pathway. After surgery, the painful swelling on the nasal side of left lower lid resolved gradually, and there were no symptomatic complications three months later. Conclusions We report the first case where a silastic sheet applied during a facial reconstruction had migrated adjacent to the lacrimal sac resulting in severe inflammation. PMID:16768193

Interaction of corneal nociceptive stimulation and lacrimal secretion.

PubMed

Situ, Ping; Simpson, Trefford L

2010-11-01

To investigate the interaction between corneal stimuli at different positions and tear secretion and to establish relationships between nociceptive stimuli detection thresholds and stimulated tearing. Using a computerized Belmonte-esthesiometer, mechanical and chemical stimuli, from 0% to 200% of the threshold in 50% steps, were delivered (in random order) to the central and peripheral (approximately 2-mm inside the limbus) cornea during four separate sessions to 15 subjects. Immediately after each stimulus, tear meniscus height (TMH) was measured using optical coherence tomography to quantify the amount of lacrimal secretion, and subjects reported whether they felt tears starting to accumulate in their eyes. Thresholds (50% detection) for detection of tearing were estimated. TMH increased with increasing stimulus intensity (P < 0.05), and the overall increase was higher with central stimulation than with peripheral stimulation (P < 0.05). The changes in TMH with threshold-scaled stimulus intensity depended on test location (P < 0.05) and stimulus modality (P < 0.05). The maximum intensity of mechanical stimulation of the central cornea induced the greatest TMH (all P < 0.05). For chemical stimulation, the stimulus intensity required to induce detectable tearing was higher than that required to detect a stimulus and higher in the periphery than at the center (all P < 0.05). Noxious mechanical and chemical stimuli evoked measurable tear secretion, with central corneal mechanical stimulation evoking the strongest lacrimation reflex. Central mechanical corneal stimulation is the most effective stimulus-position pairing and appears to be the major sensory driving force for reflex tear secretion by the lacrimal functional unit.

Postoperative long-term morbidity of extended endoscopic maxillectomy for inverted papilloma.

PubMed

Bertazzoni, G; Accorona, R; Schreiber, A; Pietrobon, G; Karligkiotis, A; Fazio, E; Castelnuovo, P; Nicolai, P

2017-12-01

Extended endoscopic maxillectomy (Sturmann-Canfield procedure) allows full visualization of the maxillary sinus by sectioning the lacrimal duct and removing the medial part of the anterior maxillary wall. The aim of this study is to evaluate the morbidity of Sturmann-Canfield procedure in patients treated for inverted papilloma. The clinical records of all patients treated with a Sturmann-Canfield procedure for inverted papilloma from October 2000 to September 2015 at two teaching hospitals were reviewed. All patients were evaluated by nasal endoscopy and lacrimal system patency was assessed. Pre-maxillary cutaneous sensitivity was tested with a Semmes-Weinstein aesthesiometer and thermic stimulation. The SNOT-22 questionnaire was administered. Patients were also asked to report any other post-surgical complaints. Fifty-nine patients were identified. Mean follow-up after surgery was 66.3 months. Mean SNOT-22 score was 5.94 (range 0-20); the majority of patients (86%) had a SNOT-22 symptom score of 3 or lower. Mucocoele occurred in 3 (5%) cases. Lacrimal pathway obstruction was observed in 7 (12%) patients. Fourteen (24%) patients complained of paraesthesia in the malar area; hypoesthesia was present in only 5 (8%) cases. Hypoesthesia in the region innervated by the anterior superior alveolar nerve was detected in 17 (29%) patients. One patient reported a slight depression of paralateronasal soft tissues. Although nasal function outcomes and the results from SNOT-22 questionnaires were favourable, a high rate of neurologic and lacrimal complications was observed. Potential morbidity of the intervention, including the possibility of negative aesthetic sequelae, should be discussed during preoperative counselling.

Transcription, Translation, and Function of Lubricin, a Boundary Lubricant, at the Ocular Surface

PubMed Central

Schmidt, Tannin A.; Sullivan, David A.; Knop, Erich; Richards, Stephen M.; Knop, Nadja; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Morrison, Sheila; Kam, Wendy R.; Sullivan, Benjamin D.

2013-01-01

Importance Lubricin may be an important barrier to the development of corneal and conjunctival epitheliopathies that may occur in dry eye disease and contact lens wear. Objective To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink and that lubricin deficiency increases shear stress on the ocular surface and promotes corneal damage. Design, Setting, and Participants Human, porcine, and mouse tissues and cells were processed for molecular biological, immunohistochemical, and tribological studies, and wild-type and PRG4 knockout mice were evaluated for corneal damage. Results Our findings demonstrate that lubricin is transcribed and translated by corneal and conjunctival epithelial cells. Lubricin messenger RNA is also present in lacrimal and meibomian glands, as well as in a number of other tissues. Absence of lubricin in PRG4 knockout mice is associated with a significant increase in corneal fluorescein staining. Our studies also show that lubricin functions as an effective friction-lowering boundary lubricant at the human cornea-eyelid interface. This effect is specific and cannot be duplicated by the use of hyaluronate or bovine serum albumin solutions. Conclusions and Relevance Our results show that lubricin is transcribed, translated, and expressed by ocular surface epithelia. Moreover, our findings demonstrate that lubricin presence significantly reduces friction between the cornea and conjunctiva and that lubricin deficiency may play a role in promoting corneal damage. PMID:23599181

Transcription, translation, and function of lubricin, a boundary lubricant, at the ocular surface.

PubMed

Schmidt, Tannin A; Sullivan, David A; Knop, Erich; Richards, Stephen M; Knop, Nadja; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Morrison, Sheila; Kam, Wendy R; Sullivan, Benjamin D

2013-06-01

Lubricin may be an important barrier to the development of corneal and conjunctival epitheliopathies that may occur in dry eye disease and contact lens wear. To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4 ]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink and that lubricin deficiency increases shear stress on the ocular surface and promotes corneal damage. Human, porcine, and mouse tissues and cells were processed for molecular biological, immunohistochemical, and tribological studies, and wild-type and PRG4 knockout mice were evaluated for corneal damage. Our findings demonstrate that lubricin is transcribed and translated by corneal and conjunctival epithelial cells. Lubricin messenger RNA is also present in lacrimal and meibomian glands, as well as in a number of other tissues. Absence of lubricin in PRG4 knockout mice is associated with a significant increase in corneal fluorescein staining. Our studies also show that lubricin functions as an effective friction-lowering boundary lubricant at the human cornea-eyelid interface. This effect is specific and cannot be duplicated by the use of hyaluronate or bovine serum albumin solutions. Our results show that lubricin is transcribed, translated, and expressed by ocular surface epithelia. Moreover, our findings demonstrate that lubricin presence significantly reduces friction between the cornea and conjunctiva and that lubricin deficiency may play a role in promoting corneal damage.

Management of functional epiphora in patients with an anatomically patent dacryocystorhinostomy.

PubMed

Shams, Pari N; Chen, Philip G; Wormald, Peter J; Sloan, Brian; Wilcsek, Geoff; McNab, Alan; Selva, Dinesh

2014-09-01

Approximately 5% to 10% of patients continue to experience persistent epiphora following an anatomically successful dacryocystorhinostomy (DCR) for nasolacrimal duct obstruction or stenosis. To investigate the management and success rate of so-called "functional failure" of DCR for nasolacrimal duct obstruction by experienced lacrimal surgeons. Multicenter retrospective case series including 5 Australian and New Zealand centers. Participants included 61 patients (71% women [n = 46]; mean age, 66 years) with functional epiphora after 65 DCRs (69% transnasal) who were recruited over a mean of 7.6 years. Inclusion criteria included confirmed preoperative diagnosis of nasolacrimal duct obstruction or stenosis, age greater than 18 years, recurrent or persistent epiphora after DCR, an anatomically successful DCR, and follow-up longer than 6 months. Exclusion criteria included evidence of lacrimal hypersecretion, eyelid malposition, and punctal or canalicular abnormalities. The number, type, timing, and success of all clinical interventions performed for the management of functional epiphora after DCR. Epiphora recurred a mean of 8.9 months after primary DCR; 89% of the cases (n = 58) had evidence of a patent ostium and 100% were patent on lacrimal irrigation. Intubation with a lacrimal stent was performed in 82% of the cases at the time of surgery, and all stents were removed a mean of 8 weeks postoperatively. Epiphora was reported immediately following DCR in 32% (n = 21) of the cases and within 6 weeks after removal of the stent in 31% (n = 20); late recurrence (>12 months after DCR) developed in 37% (n = 24) of the cases. In a total of 15% of the cases, participants declined any treatment following DCR. The remainder underwent a mean of 1.3 interventions (range, 1-3) during a mean of 23 to 41 months after primary DCR, following which 72% (n = 47) of the cases had a successful outcome; 12% (n = 8) failed to achieve improvement, and the patients declined further intervention. Thirty-nine interventions (60%) were intubation with a silicone stent with a 54% success rate. Almost half of those undergoing intubation elected to keep the stent permanently; 34% (n = 22) had an eyelid-tightening procedure with 50% success, and 15% (n = 10) required a Lester-Jones tube despite patent canaliculi, with a success rate of 90%. Functional epiphora after DCR among patients with preoperative nasolacrimal duct obstruction or stenosis appears to be uncommon. Benefits can be achieved in most patients with intubation (transient or permanent) or eyelid tightening. More than one procedure is often required.

[Effects of nootropic agents on visual functions and lacrimal antioxidative activity in patients with primary open-angle glaucoma].

PubMed

Davydova, N G; Kuznetsova, T P; Borisova, S A; Abdulkadyrova, M Zh

2006-01-01

The paper presents the results of an investigation of the effect of the nootropic agents pantogam and nooclerine on visual functions in patients with primary open-angle glaucoma. These agents have been found to have a beneficial effect on the functional activity of the retina and optic nerve, light sensitivity, hemo- and hydrodynamics of the eye.

SU-E-I-30: Image Analysis in Ultrasonography for Diagnosis of Sjoegren's Syndrome Using Dual-Tree Complex Wavelet Transform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsui, T; Ohki, M; Nakamura, T

Purpose: Sjoegren's syndrome (SS) is an autoimmune disease invading mainly salivary and lacrimal glands. Ultrasonography is used for an initial and non-invasive examination of this disease. However, the ultrasonography diagnosis tends to lack in objectivity and depends on the operator's skills. The purpose of this study is to propose a computer-aided diagnosis (CAD) system for SS based on a dual-tree complex wavelet transform (DT-CWT) and machine learning. Methods: The subjects of this study were 174 patients suspected of having SS at Nagasaki University Hospital and examined with ultrasonography of the parotid glands. Out of these patients, 77 patients were diagnosedmore » with SS by sialography. A region of interest (ROI) of 128 × 128 pixels was set within the parotid gland that was indicated by a dental radiologist. The DT-CWT was applied to the images in the ROI and every image was decomposed into 72 sub-images of the real and imaginary components in six different resolution levels and six orientations. The statistical features of the sub-image were calculated and used as data input for the support vector machine (SVM) classifier for the detection of SS. A ten-fold cross-validation was employed to verify the Resultof SVM. The accuracy of diagnosis was compared by a CAD system with a human observer performance. Results: The sensitivity, specificity, and accuracy in the detection of SS were 95%, 86%, and 91% through our CAD system respectively, while those by a human observer were 84%, 81%, and 83% respectively. Conclusion: The proposed computer-aided diagnosis system for Sjoegren's syndrome in ultrasonography based on dual-tree complex wavelet transform had a better performance than a human observer.« less

Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis.

PubMed

Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

2017-07-12

Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 10 4 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3-4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.

Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis

PubMed Central

Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

2017-01-01

Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal–oral or oral–oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 104 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3–4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission. PMID:28698666

[Evidence of lacrimal plugs via high resolution ultrasound].

PubMed

Tost, Frank H W; Darman, Jacques

2003-07-01

The practical value of high-frequency ultrasound (transducer frequency of 20 MHz) for studying lacrimal plugs positioned into canaliculi was proved. Twelve patients with twenty intracanalicular plugs and two punctum plugs were examined via high-frequency B-scan ultrasonography using 20 MHz transducer (model I3 Sacramento, USA). Detection and localisation of the intracanalicular plugs was made by a 20 MHz sector scanner. The ultrasound examinations were performed 1 - 24 month after the placement of lacrimal plugs. After patient's head positioning, the high-frequency ultrasound investigation was done via immersion fluid (2 % methylcellulose). All patients with dry eye treated by lacrimal plug implant showed echographic structure in the lacrimal canaliculus. In transversal echograms it was possible to image both canaliculi together when the lids were half-closed. Contrary to the normal state, it was not necessary to inject viscous fluid into the canaliculus. High-resolution ultrasound was able to differentiate the normal canaliculus from the findings after plug placement. The echograms can vary from one plug type to another. Highly reflective structures were found after the placement of silicone intracanalicular plugs, e. g. HERRICK-Plug. In contrast, the ultrasonic image taken through acrylic polymer intracanalicular plugs showed homogeneous small reflective inner structure, e. g. SMART-Plug. However, smooth and flat acoustic interface between acrylic polymer plug and the lacrimal canaliculus produced strong echoes. 20 MHz ultrasound seems to be well suited for the detection and localisation of intracanalicular plugs. By use of 20 MHz ultrasound scans it is possible to get high-quality images of the intracanalicular plug and around lacrimal canaliculus. Compared with UBM, the depth of penetration is much higher with negligible resolution. On the whole, we believe that 20 MHz ultrasound can become a useful tool for evaluating the placement of intracanalicular plugs after insertion.

A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies.

PubMed

Besch-Williford, Cynthia; Pesavento, Patricia; Hamilton, Shari; Bauer, Beth; Kapusinszky, Beatrix; Phan, Tung; Delwart, Eric; Livingston, Robert; Cushing, Susan; Watanabe, Rie; Levin, Stephen; Berger, Diana; Myles, Matthew

2017-07-01

We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland. Unbiased viral metagenomic sequencing of lesioned tissues identified a novel polyomavirus, provisionally named Rattus norvegicus polyomavirus 2 (RatPyV2), which clustered with Washington University (WU) polyomavirus in the Wuki clade of the Betapolyomavirus genus. In situ hybridization analyses and quantitative polymerase chain reaction (PCR) results demonstrated viral nucleic acids in epithelium of respiratory, glandular, and reproductive tissues. Polyomaviral disease was reproduced in Foxn1 rnu nude rats cohoused with infected rats or experimentally inoculated with virus. After development of RatPyV2-specific diagnostic assays, a survey of immune-competent rats from North American research institutions revealed detection of RatPyV2 in 7 of 1,000 fecal samples by PCR and anti-RatPyV2 antibodies in 480 of 1,500 serum samples. These findings suggest widespread infection in laboratory rat populations, which may have profound implications for established models of respiratory injury. Additionally, RatPyV2 infection studies may provide an important system to investigate the pathogenesis of WU polyomavirus diseases of man.

Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjögren's Syndrome

PubMed Central

Meng, Zhen; Edman, Maria C.; Hsueh, Pang-Yu; Chen, Chiao-Yu; Klinngam, Wannita; Tolmachova, Tanya; Okamoto, Curtis T.

2016-01-01

The mechanism responsible for the altered spectrum of tear proteins secreted by lacrimal gland acinar cells (LGAC) in patients with Sjögren's Syndrome (SS) remains unknown. We have previously identified increased cathepsin S (CTSS) activity as a unique characteristic of tears of patients with SS. Here, we investigated the role of Rab3D, Rab27a, and Rab27b proteins in the enhanced release of CTSS from LGAC. Similar to patients with SS and to the male nonobese diabetic (NOD) mouse model of SS, CTSS activity was elevated in tears of mice lacking Rab3D. Findings of lower gene expression and altered localization of Rab3D in NOD LGAC reinforce a role for Rab3D in suppressing excess CTSS release under physiological conditions. However, CTSS activity was significantly reduced in tears of mice lacking Rab27 isoforms. The reliance of CTSS secretion on Rab27 activity was supported by in vitro findings that newly synthesized CTSS was detected in and secreted from Rab27-enriched secretory vesicles and that expression of dominant negative Rab27b reduced carbachol-stimulated secretion of CTSS in cultured LGAC. High-resolution 3D-structured illumination microscopy revealed microdomains of Rab3D and Rab27 isoforms on the same secretory vesicles but present in different proportions on different vesicles, suggesting that changes in their relative association with secretory vesicles may tailor the vesicle contents. We propose that a loss of Rab3D from secretory vesicles, leading to disproportionate Rab27-to-Rab3D activity, may contribute to the enhanced release of CTSS in tears of patients with SS. PMID:27076615

Endoscopic Dacrocystorhinostomy in Lacrimal Canalicular Trauma

PubMed Central

Khan, Humayun A; Bayat, Aredeshir; De Carpentier, JP

2007-01-01

A case is presented where the common insertion of the upper and lower canaliculus of the lacrimal sac was repaired using endoscopic dacrocystorhinostomy (DCR) techniques, with silicone stenting and securing of stents intranasally. PMID:17316509

Is salivary gland function altered in noninsulin-dependent diabetes mellitus and obesity-insulin resistance?

PubMed

Ittichaicharoen, Jitjiroj; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2016-04-01

Salivary gland dysfunction in several systemic diseases has been shown to decrease the quality of life in patients. In non-insulin dependent diabetes mellitus (NIDDM), inadequate salivary gland function has been evidenced to closely associate with this abnormal glycemic control condition. Although several studies demonstrated that NIDDM has a positive correlation with impaired salivary gland function, including decreased salivary flow rate, some studies demonstrated contradictory findings. Moreover, the changes of the salivary gland function in pre-diabetic stage known as insulin resistance are still unclear. The aim of this review is to comprehensively summarize the current evidence from in vitro, in vivo and clinical studies regarding the relationship between NIDDM and salivary gland function, as well as the correlation between obesity and salivary gland function. Consistent findings as well as controversial reports and the mechanistic insights regarding the effect of NIDDM and obesity-insulin resistance on salivary gland function are also presented and discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid.

PubMed

Kimura, Yuki; Mori, Daisuke; Imada, Toshihiro; Izuta, Yusuke; Shibuya, Michiko; Sakaguchi, Hisayo; Oonishi, Erina; Okada, Naoko; Matsumoto, Kenji; Tsubota, Kazuo

2017-04-05

Sea buckthorn ( Hippophae rhamnoides ) -derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid

PubMed Central

Nakamura, Shigeru; Kimura, Yuki; Mori, Daisuke; Imada, Toshihiro; Izuta, Yusuke; Shibuya, Michiko; Sakaguchi, Hisayo; Oonishi, Erina; Okada, Naoko; Matsumoto, Kenji; Tsubota, Kazuo

2017-01-01

Sea buckthorn (Hippophae rhamnoides)–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye. PMID:28379171

Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.

PubMed

Miner, Jonathan J; Sene, Abdoulaye; Richner, Justin M; Smith, Amber M; Santeford, Andrea; Ban, Norimitsu; Weger-Lucarelli, James; Manzella, Francesca; Rückert, Claudia; Govero, Jennifer; Noguchi, Kevin K; Ebel, Gregory D; Diamond, Michael S; Apte, Rajendra S

2016-09-20

Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

[Orbital inflammation].

PubMed

Mouriaux, F; Coffin-Pichonnet, S; Robert, P-Y; Abad, S; Martin-Silva, N

2014-12-01

Orbital inflammation is a generic term encompassing inflammatory pathologies affecting all structures within the orbit : anterior (involvement up to the posterior aspect of the globe), diffuse (involvement of intra- and/or extraconal fat), apical (involvement of the posterior orbit), myositis (involvement of only the extraocular muscles), dacryoadenitis (involvement of the lacrimal gland). We distinguish between specific inflammation and non-specific inflammation, commonly referred to as idiopathic inflammation. Specific orbital inflammation corresponds to a secondary localization of a "generalized" disease (systemic or auto-immune). Idiopathic orbital inflammation corresponds to uniquely orbital inflammation without generalized disease, and thus an unknown etiology. At the top of the differential diagnosis for specific or idiopathic orbital inflammation are malignant tumors, represented most commonly in the adult by lympho-proliferative syndromes and metastases. Treatment of specific orbital inflammation begins with treatment of the underlying disease. For idiopathic orbital inflammation, treatment (most often corticosteroids) is indicated above all in cases of visual loss due to optic neuropathy, in the presence of pain or oculomotor palsy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Normative dimensions and symmetry of the lacrimal drainage system on dacryocystography: statistical analysis of morphometric characteristics.

PubMed

Horsburgh, A; Massoud, T F

2013-05-01

Asymmetric lacrimal flow occurs in females more than males. We hypothesised that the normal lacrimal drainage system (LDS) may show subtle left-right asymmetry in morphometry when imaged on dacryocystography (DCG). We retrospectively reviewed 60 normal bilateral LDSs.Images were analysed for 7 parameters: (1) combined length of either the superior or inferior canaliculus plus common canaliculus, (2) angle of insertion of common canaliculus into lacrimal sac (LS), (3, 4) length and width of the LS, (5) length of the naso lacrimal duct (NLD), and (6, 7) width of proximal and distal NLD. We tested the effect of independent variables (age, gender, and side) on each dependent variable (length, width, or angle) using regression analysis. We used a Studentt-test for independent samples to statistically compare bilateral LDSs. Patient median age was 62 years, and male:female ratio was 27:73. Mean dimensions and angles for all LDSs were: (1) 14.5 mm, (2) 57°,(3) 11.6 mm, (4) 2.1 mm, (5) 20.7 mm, (6) 1.4 mm, and (7) 1.8 mm. No independent variable affected variation in length, width, or angle. No significant difference emerged between dimensions of right and left LDSs in both sexes. A degree of affective lateralisation in the brain is known to result in lacrimal flow asymmetry after mood manipulation. We show that this is not reflected in LDS anatomy. Moreover, our detailed morphometric data can aid in therapeutic planning of LDS luminal procedures, especially when DCG images of one LDS are used as a road map for contralateral interventions.

A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system.

PubMed

Ferrero, David M; Moeller, Lisa M; Osakada, Takuya; Horio, Nao; Li, Qian; Roy, Dheeraj S; Cichy, Annika; Spehr, Marc; Touhara, Kazushige; Liberles, Stephen D

2013-10-17

Animals display a repertoire of different social behaviours. Appropriate behavioural responses depend on sensory input received during social interactions. In mice, social behaviour is driven by pheromones, chemical signals that encode information related to age, sex and physiological state. However, although mice show different social behaviours towards adults, juveniles and neonates, sensory cues that enable specific recognition of juvenile mice are unknown. Here we describe a juvenile pheromone produced by young mice before puberty, termed exocrine-gland secreting peptide 22 (ESP22). ESP22 is secreted from the lacrimal gland and released into tears of 2- to 3-week-old mice. Upon detection, ESP22 activates high-affinity sensory neurons in the vomeronasal organ, and downstream limbic neurons in the medial amygdala. Recombinant ESP22, painted on mice, exerts a powerful inhibitory effect on adult male mating behaviour, which is abolished in knockout mice lacking TRPC2, a key signalling component of the vomeronasal organ. Furthermore, knockout of TRPC2 or loss of ESP22 production results in increased sexual behaviour of adult males towards juveniles, and sexual responses towards ESP22-deficient juveniles are suppressed by ESP22 painting. Thus, we describe a pheromone of sexually immature mice that controls an innate social behaviour, a response pathway through the accessory olfactory system and a new role for vomeronasal organ signalling in inhibiting sexual behaviour towards young. These findings provide a molecular framework for understanding how a sensory system can regulate behaviour.

Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations.

PubMed

Elmaleh-Bergès, M; Baumann, C; Noël-Pétroff, N; Sekkal, A; Couloigner, V; Devriendt, K; Wilson, M; Marlin, S; Sebag, G; Pingault, V

2013-01-01

Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.

Pharmacological Activation of the EDA/EDAR Signaling Pathway Restores Salivary Gland Function following Radiation-Induced Damage

PubMed Central

Hill, Grace; Headon, Denis; Harris, Zoey I.; Huttner, Kenneth; Limesand, Kirsten H.

2014-01-01

Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage. PMID:25409170

A novel technique for ventral orbital stabilization: the masseter muscle flap.

PubMed

Sivagurunathan, Amilan; Boy, Sonja C; Steenkamp, Gerhard

2014-01-01

Loss of the caudal maxilla and ventral orbit after tumor resections can have negative functional and esthetic influences on the eye involved. This article reports on a case of a caudal maxillary acanthomatous ameloblastoma involving the ventral orbit that was resected and stabilized with a masseter muscle flap. The masseter muscle flap was generated from the superficial belly of the masseter muscle in order to close a defect in the orbital rim, created by a caudal maxillectomy. None of the published complications such as enophthalmos, excessive lacrimation, globe deviation, or strabismus were noted, 8 months following the procedure. The only clinical sign present at the time of re-evaluation was mild lacrimation. The authors propose the use of a masseter muscle flap as a viable technique in stabilizing the ventral orbit after caudal maxillectomy and ventral orbitectomy, preventing the complications associated with this surgery. © 2013 American College of Veterinary Ophthalmologists.

An alternative method of closed silicone intubation of the lacrimal system.

PubMed

Henderson, P N; McNab, A A

1996-05-01

An alternative method of closed lacrimal intubation is described, the basis of which is to place the end of a piece of silicone tubing over the end of a small-diameter metal introducer, stretch the silicone tubing back along the introducer, and then pass the introducer together with the tubing through the lacrimal system into the nasal cavity. The tubing is visualized in the inferior meatus, from where it is retrieved, and then the introducer is withdrawn. The other end of the tubing is passed in a similar fashion. The technique is easily mastered, inexpensive, and less traumatic than other described techniques.

The pineal gland from development to function.

PubMed

Sapède, Dora; Cau, Elise

2013-01-01

The pineal gland is a small neuroendocrine organ whose main and most conserved function is the nighttime secretion of melatonin. In lower vertebrates, the pineal gland is directly photosensitive. In contrast, in higher vertebrates, the direct photosensitivity of the pineal gland had been lost. Rather, the action of this gland as a relay between environmental light conditions and body functions involves reception of light information by the retina. In parallel to this sensory regression, the pineal gland (and its accessory organs) appears to have lost several functions in relation to light and temperature, which are important in lower vertebrate species. In humans, the functions of the pineal gland overlap with the functions of melatonin. They are extremely widespread and include general effects both on cell protection and on more precise functions, such as sleep and immunity. Recently, the role of melatonin has received a considerable amount of attention due to increased cancer risk in shift workers and the discovery that patients suffering from neurodegenerative diseases, autism, or depression exhibit abnormal melatonin rhythms. © 2013 Elsevier Inc. All rights reserved.

Ultrastructure of the Intramandibular Gland of Workers and Queens of the Stingless Bee, Melipona quadrifasciata

PubMed Central

Da Cruz-Landim, Carminda; Gracioli-Vitti, Luciana F.; Abdalla, Fábio C.

2011-01-01

The intramandibular glands of workers and queens of Melipona quadrifasciata Lepeletier (Hymenoptera: Apidae), at different ages and from different functional groups, were studied using light and transmission electron microscopy. The results demonstrated that these glands are composed of two types of secretory structures: 1.A hypertrophied epidermis on the dorsal side of the mandible that is an epithelial gland. 2. Free secretory cells filling the inner spaces of the appendices that constitute a unicellular gland. The epithelial gland is larger in the young (1-2-day-old workers), and the gland becomes involuted during the nurse worker stage. The unicellular glands of the workers posses some secretion during all of the studied phases, but secretory activity is more intensive in the foraging workers. Vesicles of secretion are absent in the unicellular glands of queens. These results demonstrate that these glands show functional adaptations in different castes corresponding to the functions of each caste. PMID:22220493

Ultrastructure of the intramandibular gland of workers and queens of the stingless bee, Melipona quadrifasciata.

PubMed

Da Cruz-Landim, Carminda; Gracioli-Vitti, Luciana F; Abdalla, Fábio C

2011-01-01

The intramandibular glands of workers and queens of Melipona quadrifasciata Lepeletier (Hymenoptera: Apidae), at different ages and from different functional groups, were studied using light and transmission electron microscopy. The results demonstrated that these glands are composed of two types of secretory structures: 1.A hypertrophied epidermis on the dorsal side of the mandible that is an epithelial gland. 2. Free secretory cells filling the inner spaces of the appendices that constitute a unicellular gland. The epithelial gland is larger in the young (1-2-day-old workers), and the gland becomes involuted during the nurse worker stage. The unicellular glands of the workers posses some secretion during all of the studied phases, but secretory activity is more intensive in the foraging workers. Vesicles of secretion are absent in the unicellular glands of queens. These results demonstrate that these glands show functional adaptations in different castes corresponding to the functions of each caste.

Molecular Analysis of the Human Autoantibody Response to α-Fodrin in Sjögren’s Syndrome Reveals Novel Apoptosis-Induced Specificity

PubMed Central

Maruyama, Toshiaki; Saito, Ichiro; Hayashi, Yoshio; Kompfner, Elizabeth; Fox, Robert I.; Burton, Dennis R.; Ditzel, Henrik J.

2004-01-01

Lymphocyte infiltration of salivary and lacrimal glands leading to diminished secretion and gland destruction as a result of apoptosis is thought to be pivotal in the pathogenesis of Sjögren’s syndrome (SS). The cytoskeletal protein α-fodrin is cleaved during this apoptotic process, and a strong antibody (Ab) response is elicited to a 120-kd fragment of cleaved α-fodrin in the majority of SS patients, but generally not in other diseases in which apoptosis also occurs. Little is known about the anti-α-fodrin autoantibody response on a molecular level. To address this issue, IgG phage display libraries were generated from the bone marrow of two SS donors and a panel of anti-α-fodrin IgGs was isolated by selection on α-fodrin immunoblots. All of the human monoclonal Abs (hmAbs) reacted with a 150-kd fragment and not with the 120-kd fragment or intact α-fodrin, indicating that the epitope recognized became exposed after α-fodrin cleavage. Analysis of a large panel of SS patients (defined by the strict San Diego diagnostic criteria) showed that 25% of SS sera exhibited this 150-kd α-fodrin specificity. The hmAbs stained human cultured salivary acinar cells and the staining was redistributed to surface blebs during apoptosis. They also stained inflamed acinar/ductal epithelial cells in SS salivary tissue biopsies, and only partially co-localized with monoclonal Abs recognizing the full-length α-fodrin. Our study shows that in SS patients, neoepitopes on the 150-kd cleaved product of α-fodrin become exposed to the immune system, frequently eliciting anti-150-kd α-fodrin Abs in addition to the previously reported anti-120-kd Abs. The anti-150-kd α-fodrin hmAbs may serve as valuable reagents for the study of SS pathogenesis and diagnostic analyses of SS salivary gland tissue. PMID:15215161

Purification, characterization and immunolocalization of porcine surfactant protein D

PubMed Central

Soerensen, C M; Nielsen, O L; Willis, A; Heegaard, P M H; Holmskov, U

2005-01-01

Surfactant protein D (SP-D) is a collectin believed to play an important role in innate immunity. SP-D is characterized by having a collagen-like domain and a carbohydrate recognition domain (CRD), which has a specific Ca2+-dependent specificity for saccharides and thus the ability to bind complex glycoconjugates on micro-organisms. This paper describes the tissue immunolocalization of porcine SP-D (pSP-D) in normal slaughter pigs using a monoclonal antibody raised against purified pSP-D. Porcine SP-D was purified from porcine bronchoalveolar lavage (BAL) by maltose-agarose and immunoglobulin M affinity chromatography. The purified protein appeared on sodium dodecyl sulphate–polyacrylamide gel electrophoresis as a band of ∼53 000 MW in the reduced state and ∼138 000 MW in the unreduced state. Porcine SP-D was sensitive to collagenase digestion and N-deglycosylation, which reduced the molecular mass to ∼24 000 MW and ∼48 000 MW respectively, in the reduced state. N-deglycosylation of the collagen-resistant fragment, reduced the molecular mass to ∼21 000 MW showing the presence of an N-glycosylation site located in the CRD. Porcine SP-D bound to solid-phase mannan in a dose and Ca2+-dependent manner with a saccharide specificity similar to rat and human SP-D. The purified protein was used for the production of a monoclonal anti-pSP-D antibody. The antibody reacted specifically with pSP-D in the reduced and unreduced state when analysed by Western blotting. Immunohistochemical evaluation of normal porcine tissues showed pSP-D immunoreactivity predominantly in Clara cells and serous cells of the bronchial submucosal glands, and to a lesser extent in alveolar type II cells, epithelial cells of the intestinal glands (crypts of Lieberkühn) in the duodenum, jejunum and ileum and serous cells of the dorsolateral lacrimal gland. PMID:15606797

A mucin-like glycoprotein identified by MAG (mouse ascites Golgi) antibodies. Menstrual cycle-dependent localization in human endometrium.

PubMed Central

Kliman, H. J.; Feinberg, R. F.; Schwartz, L. B.; Feinman, M. A.; Lavi, E.; Meaddough, E. L.

1995-01-01

Human endometrial glands synthesize and secrete a high molecular weight mucin-like glycoprotein in a menstrual cycle-dependent fashion. A novel moiety within this Golgi-associated glycoprotein is strongly reactive with IgG antibodies in numerous murine ascites, and has been termed MAG (mouse ascites Golgi). Immunohistochemical staining of 201 endometrial biopsies revealed the following patterns: MAG first appeared in the Golgi on cycle day 5, peaked on day 15, was present on the surface of the luminal epithelium between days 17 and 19, and was no longer detectable after day 19. MAG was also present in cervical, prostate, seminal vesicle, and lacrimal glands, pancreatic acinar cells, gall bladder and bile duct epithelium, and certain cells of the salivary and sweat glands. Interestingly, only tissues from blood group A individuals exhibited this staining. As a common link among all these cell types is the expression of mucins, we speculated that the MAG epitope could be a mucin-associated blood group A-related epitope. This hypothesis was tested by absorption experiments with a variety of glycoconjugates and erythrocytes and by immunoblots of MAG-rich material. The absorption studies demonstrated that only type III porcine mucin (< 1% sialic acid) and blood type A or AB erythrocytes were able to absorb the anti-MAG antibody. Inasmuch as N-acetyl-galactosamine alone, the terminal blood group A carbohydrate, did not block MAG antibody binding, the MAG epitope appears to involve N-acetylgalactosamine plus other determinants. Immunoblots of endometrial extracts and saliva from blood type A individuals revealed MAG-reactive material with a molecular weight > 200 kd under reducing conditions. Because the MAG epitope appears on the endometrial surface during the purported implantation window, we speculate that mucin-like epitopes could play a role in the earliest apposition phases of conceptus-endometrial interaction. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 PMID:7531946

Diffusion-Weighted Magnetic Resonance Imaging to Evaluate Major Salivary Gland Function Before and After Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dirix, Piet; Keyzer, Frederik de; Vandecaveye, Vincent

2008-08-01

Purpose: To evaluate diffusion-weighted (DW)-MRI as a noninvasive tool to investigate major salivary gland function before and after radiotherapy (RT) for head and neck cancer (HNC). Methods and Materials: DW-MRI was performed in 8 HNC patients before and after parotid-sparing RT (mean dose to the contralateral parotid gland <26 Gy). A DW sequence was performed once at rest and then repeated continuously during salivary stimulation. Apparent diffusion coefficient (ADC) maps for both parotid and submandibular glands were calculated. Findings were compared with salivary gland scintigraphy. Results: Before RT, the mean ADC value at rest was significantly lower in the parotidmore » than in the submandibular glands. During the first 5 min of stimulation, the ADC value of the salivary glands showed a decrease, followed by a steady increase until a peak ADC, significantly higher than the baseline value, was reached after a median of 17 min. The baseline ADC value at rest was significantly higher after RT than before RT in the nonspared salivary glands but not in the spared parotid glands. In the contralateral parotid glands, the same response was seen as before RT. This pattern was completely lost in the nonspared glands. These results corresponded with remaining or loss of salivary function, respectively, as confirmed by salivary gland scintigraphy. Conclusions: Diffusion-weighted-MRI allows noninvasive evaluation of functional changes in the major salivary glands after RT and is a promising tool for investigating radiation-induced xerostomia.« less

Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

PubMed

Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

2016-06-01

Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

Transitional neoplasms of the naso-lacrimal system: A review of the histopathology and histogenesis☆

PubMed Central

Heathcote, J. Godfrey

2012-01-01

Transitional papilloma (inverted papilloma, Schneiderian papilloma) is a relatively common, benign epithelial neoplasm of the sinonasal tract that also occurs in the lacrimal drainage system. The name transitional papilloma is recommended because it reflects the key histological features required for pathological diagnosis, as well as the histogenesis of the tumour. The histogenesis of the tumour is reviewed, together with its natural history, which is characterized by bone remodelling and destruction, a tendency to recur and to undergo malignant transformation. Biomarkers associated with these features have been identified in the sinonasal tumours and may also be of relevance to the lacrimal sac tumours, although the necessary studies have not yet been undertaken. PMID:23960982

A Case of Recurrent Schneiderian Papilloma of the Lacrimal Sac Invading the Nasal Cavity

PubMed Central

Jang, Ji Hye; Choe, Mi Sun

2009-01-01

A 44-year-old man presented with a history of chronic epiphora, discharge from the right eye, and a palpable mass in the medial canthal area. Irrigation of the lacrimal system revealed bloody discharge. Orbital magnetic resonance imaging (MRI) showed a well-defined heterogeneous enhanced mass filling the lacrimal sac and upper nasolacrimal duct (NLD). A wide excision and surgical biopsy were performed. Histopathology showed the tumor to be an exophytic Schneiderian papilloma with moderate to severe dysplasia. Three months later, the mass was found to be invading the nasal cavity through the NLD. Endoscopic histopathological evaluation confirmed that it was identical to the originally identified papilloma. PMID:19568358

A novel cell-based assay for inhibitory anti-muscarinic type 3 receptor antibodies in primary Sjögren's syndrome.

PubMed

Bastian, Isabell; Gordon, Tom P; Jackson, Michael W

2015-12-01

Inhibitory autoantibodies acting at the muscarinic acetylcholine receptor type 3 (M3R) are postulated to mediate autonomic dysfunction, including decreased salivary and lacrimal gland output and extra-glandular manifestations, in patients with primary Sjögren's syndrome. However, the contention that anti-M3R antibodies are pathogenic in patients remains untested, due to a lack of assays both sophisticated enough to detect inhibitory anti-M3R antibodies yet suitable for screening large patient cohorts. In the current study, we have established a cell-based bioassay of M3R activity, based on dual transfection of the M3R and a luciferase reporter gene. The bioassay is capable of capturing real-time agonist-mediated signalling of the M3R, which is inhibited specifically by patient IgG that have previously been demonstrated to have anti-M3R activity. The assay can be run in multi-well culture plates, and analysed using simple luminescence readers. As such, the new bioassay incorporating M3R-mediated luciferase transduction is the first assay adaptable to common diagnostic platforms that is capable of determining the presence in patient serum of functionally active anti-M3R autoantibodies. The new bioassay should prove useful for large cohort screening studies aiming to correlate the presence in patients of inhibitory anti-M3R antibodies with symptoms of both glandular and extra-glandular autonomic dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

[Morphofunctional and molecular bases of pineal gland aging].

PubMed

Khavinson, V Kh; Lin'kova, N S

2012-01-01

The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction. The pineal gland is central organ, which regulates activity of neuroimmunoendocrine, antioxidant and other organisms systems. Functional activity of pineal gland is discreased at aging, which is the reason of melatonin level changing. The molecular and morphology research demonstrated, that pineal gland hadn't strongly pronounced atrophy at aging. Long-term experience showed, that peptides extract of pineal gland epithalamin and synthetic tetrapeptide on it base epithalon restored melatonin secretion in pineal gland and had strong regulatory activity at neuroimmunoendocrine and antioxidant organism systems.

Double silicone tube intubation for the management of partial lacrimal system obstruction.

PubMed

Demirci, Hakan; Elner, Victor M

2008-02-01

To evaluate the effectiveness of double silicone intubation for the management of partial lacrimal drainage system obstruction in adults. Observational retrospective case series. Twenty-four eyes of 18 consecutive adult patients with partial lacrimal system obstruction managed at the University of Michigan. Retrospective review of symptoms and signs, duration of silicone intubation, and complications. Resolution of tearing. Preoperative tearing, negative Jones I testing, positive Jones II testing, and resistance to positive-pressure irrigation were present in all eyes (100%). The first silicone tube was removed after a mean of 11+/-7 months, and the second tube after 16+/-6 months. Postoperatively, at a mean of 21+/-9 months after removal of both tubes, tearing remained resolved in 19 eyes (79%) and remained improved in 2 eyes (8%). In eyes with resolved tearing, Jones I testing became positive, and there was no resistance to positive-pressure irrigation. Persistent tearing in 3 eyes (13%) required treatment with external dacryocystorhinostomy. The only complication was peripunctal pyogenic granulomas in 2 eyes. Double silicone intubation is an effective minimally invasive technique for treatment of partial lacrimal system obstruction in adults.

[Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people].

PubMed

Korkushko, O V; Lapin, B A; Goncharova, N D; Khavinson, V Kh; Shatilo, V B; Vengerin, A A; Antoniuk-Shcheglova, I A; Magdich, L V

2007-01-01

In the course of aging both monkeys and people reveal decreased night and average daily level of melatonin in the blood plasma and reduced hormone circadian rhythm amplitude, which evidence the disorder of the pineal gland melatonin releasing function. Peptide preparations of the pineal gland (Epithalamin--a complex of peptides isolated from the pineal gland and Epitalon--synthetic tetrapeptide) recover night release of endogenous melatonin and lead to the normalization of the hormone circadian rhythm in the blood plasma. In elderly people Epithalamin and Epitalon modulate pineal gland functional state: people with pineal gland functional insufficiency report an increase of night melatonin level. The preparations of the pineal gland, effectively increasing melatonin concentration and having no side effects, can be used in clinical geriatric practice.

Identification of factors that function in Drosophila salivary gland cell death during development using proteomics

PubMed Central

McPhee, C K; Balgley, B M; Nelson, C; Hill, J H; Batlevi, Y; Fang, X; Lee, C S; Baehrecke, E H

2013-01-01

Proteasome inhibitors induce cell death and are used in cancer therapy, but little is known about the relationship between proteasome impairment and cell death under normal physiological conditions. Here, we investigate the relationship between proteasome function and larval salivary gland cell death during development in Drosophila. Drosophila larval salivary gland cells undergo synchronized programmed cell death requiring both caspases and autophagy (Atg) genes during development. Here, we show that ubiquitin proteasome system (UPS) function is reduced during normal salivary gland cell death, and that ectopic proteasome impairment in salivary gland cells leads to early DNA fragmentation and salivary gland condensation in vivo. Shotgun proteomic analyses of purified dying salivary glands identified the UPS as the top category of proteins enriched, suggesting a possible compensatory induction of these factors to maintain proteolysis during cell death. We compared the proteome following ectopic proteasome impairment to the proteome during developmental cell death in salivary gland cells. Proteins that were enriched in both populations of cells were screened for their function in salivary gland degradation using RNAi knockdown. We identified several factors, including trol, a novel gene CG11880, and the cop9 signalsome component cop9 signalsome 6, as required for Drosophila larval salivary gland degradation. PMID:22935612

Periorbital and Intraorbital Studies of the Terminal Branches of the Ophthalmic Artery for Periorbital and Glabellar Filler Placements.

PubMed

Tansatit, Tanvaa; Apinuntrum, Prawit; Phetudom, Thavorn

2017-06-01

Filler injections for sunken upper eyelid correction and glabellar augmentation at the orbitoglabellar region need to be performed correctly. Precise knowledge of the emerging sites of all terminal branches of the ophthalmic artery is essential for these procedures to be conducted safely. The terminal branches of the ophthalmic artery were studied in both periorbital and intraorbital dissections. The aim of this study was to verify the critical positions of the emerging sites at the orbital septum that may act as potential retrograde channels for filler emboli. In the 40 eyes examined, the branches of the ophthalmic artery were found to emerge from four different sites. Two substantial emerging sites were situated on both sides of the trochlea of the superior oblique muscle. These sites were located at the superior part of the medial orbital rim (SMOR) and are alternatively named as the epitrochlear and the subtrochlear emerging sites. The other two sites can be regarded as accessory emerging sites due to the comparably smaller artery. Dissection of the intraorbital region revealed small periosteal branches of the infraorbital artery which coursed anteriorly on the orbital floor to form anastomoses with the lacrimal artery. In other areas of the orbital floor, no branches extended from the infraorbital artery. In front of the lacrimal gland, very minute branches descended and coursed along both margins of the superior tarsus but did not course outside the lateral orbital rim. A danger zone was located at the SMOR, where the ophthalmic branches emerge to form anastomotic channels. Compression at the trochlea guarantees safe injection of filler, reducing the risk of complication. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lacrimal secretion stimulants: sigma receptors and drug implications.

PubMed

Shirolkar, S; Schoenwald, R D; Barfknecht, C F; Xia, E; Cheng, B; Iwai, Y; Ignace, C C; Vidvauns, S; Newton, R E

1993-01-01

3H-DTG (1.3-di(2-[5-3H]tolyl)guanidine) or 3H-haloperidol was added to sigma-receptors (25 nM) in the presence of 25 nM spiperone and incubated with increasing concentrations of bromhexine derivatives (phenylalkylamines; 10(-9) to 10(-2)M) in membrane homogenate suspensions. IC50 values for two derivatives ranged from 3.2 to 8.8 nM for both radioligands. A preferred derivative, 7A (N,N'-dimethyl-2-phenyl-ethylamine), yielded an IC50 of 7.8 nM for 3H-haloperidol but showed much less affinity in displacing 3H-DTG (IC50 = 900 nM). Applying the technic of Bromberg [Exp. Eye Res., 40:313-320, 1985], in vitro protein secretion rates were measured following stimulation of either lacrimal gland slices or isolated, intact lacrimocytes with the compounds. In vitro protein secretion rates exhibit a dose-response relationship with increases in protein release up to a concentration of 10(-8) to 10(-4) M for various derivatives of bromhexine and 10(-4) M for carbachol. By means of Schirmer strips, tear fluid was collected over a five minute period at 10 and 60 minutes post-dosing following the topical application (50 microliters) to the right eye of New Zealand white rabbits (n = 20-24) of 7A at various concentrations. Incubation of lacrimocytes with 7A alone (10(-4) M), with haloperidol (10(-4) M) alone or in combination show that 7A is acting as an agonist to stimulate protein release, whereas haloperidol is acting as an antagonist to inhibit release. In vivo protein secretion rates also show a dose-response curve (at both 10 and 60 minutes post-dosing) for 7A that reach a statistically significant maximum in the dosed eye at a concentration of 0.15% w/v. Analysis of protein extracts using size exclusion HPLC shows an increase in secretory proteins, particularly tear-specific prealbumin.

Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease

PubMed Central

Farid, Marjan; Agrawal, Anshu; Fremgen, Daniel; Tao, Jeremiah; Chuyi, He; Nesburn, Anthony B.; BenMohamed, Lbachir

2014-01-01

Dry eye disease (DED) is a prevalent public health concern that affects up to 30% of adults and is particularly chronic and severe in the elderly. Two interconnected mechanisms cause DED: (1) an age-related dysfunction of lacrimal and meibomian glands, which leads to decreased tear production and/or an increase in tear evaporation; and (2) an age-related uncontrolled inflammation of the surface of the eye triggered by yet-to-be-determined internal immunopathological mechanisms, independent of tear deficiency and evaporation. In this review we summarize current knowledge on animal models that mimic both the severity and chronicity of inflammatory DED and that have been reliably used to provide insights into the immunopathological mechanisms of DED, and we provide an overview of the opportunities and limitations of the rabbit model in investigating the role of both ocular and nasal mucosal immune systems in the immunopathology of inflammatory DED and in testing novel immunotherapies aimed at delaying or reversing the uncontrolled age-related inflammatory DED. PMID:25535823

A chimeric human-mouse model of Sjögren's syndrome.

PubMed

Young, Nicholas A; Wu, Lai-Chu; Bruss, Michael; Kaffenberger, Benjamin H; Hampton, Jeffrey; Bolon, Brad; Jarjour, Wael N

2015-01-01

Despite recent advances in the understanding of Sjögren's Syndrome (SjS), the pathogenic mechanisms remain elusive and an ideal model for early drug discovery is not yet available. To establish a humanized mouse model of SjS, peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with SjS were transferred into immunodeficient NOD-scid IL-2rγ(null) mouse recipients to produce chimeric mice. While no difference was observed in the distribution of cells, chimeric mice transferred with PBMCs from SjS patients produced enhanced cytokine levels, most significantly IFN-γ and IL-10. Histological examination revealed enhanced inflammatory responses in the lacrimal and salivary glands of SjS chimeras, as measured by digital image analysis and blinded histopathological scoring. Infiltrates were primarily CD4+, with minimal detection of CD8+ T-cells and B-cells. These results demonstrate a novel chimeric mouse model of human SjS that provides a unique in vivo environment to test experimental therapeutics and investigate T-cell disease pathology. Copyright © 2014. Published by Elsevier Inc.

(+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride) induces saliva and tear secretions in rats and mice: the role of muscarinic acetylcholine receptors.

PubMed

Iga, Y; Arisawa, H; Ogane, N; Saito, Y; Tomizuka, T; Nakagawa-Yagi, Y; Masunaga, H; Yasuda, H; Miyata, N

1998-11-01

We investigated effects of (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride), a rigid analogue of acetylcholine, on saliva and tear secretions in rats and mice to evaluate its therapeutical efficacy for xerostomia and xerophthalmia in patients with Sjogren's syndrome and X-ray exposure in the head and neck. Intraduodenal administrations of SNI-2011 increased saliva secretion in a dose-dependent manner at doses ranging from 3 to 30 mg/kg in normal rats and mice, two strains of autoimmune disease mice and X-irradiated saliva secretion defective rats. The salivation elicited by SNI-2011 was completely inhibited by atropine. A similar atropine-sensitive response was observed in tear secretion. In rat submandibular/sublingual gland membranes, [3H]quinuclidinyl benzilate (QNB) binding was saturable, and Scatchard plot analysis revealed a single population of binding sites with a Kd of 22 pM and a maximal binding capacity of 60 fmol/mg protein. The competitive inhibition curve of the [3H]QNB binding by SNI-2011 was obtained, and its dissociation constant value calculated from IC50 was 1-2 microM. These results suggest that SNI-2011 increases saliva and tear secretions through a direct stimulation to muscarinic receptors in salivary and lacrimal glands, and they suggest that SNI-2011 should be beneficial to patients with Sjögren's syndrome and X-ray exposure in the head and neck.

Primary Sjögren Syndrome in Han Chinese

PubMed Central

Zhao, Yun; Li, Ya; Wang, Li; Li, Xiao-Feng; Huang, Ci-Bo; Wang, Guo-Chun; Zhang, Xue-Wu; Zhang, Zhuo-Li; Zhang, Xiao; Xiao, Wei-Guo; Dai, Lie; Wang, Yong-Fu; Hu, Shao-Xian; Li, Hong-Bin; Gong, Lu; Liu, Bin; Sun, Ling-Yun; Zhang, Miao-Jia; Zhang, Xuan; Li, Yong-Zhe; Du, De-Shun; Zhang, Shun-Hua; Sun, Yuan-Yuan; Zhang, Feng-Chun

2015-01-01

Abstract The epidemiological characteristics of Sjögren syndrome (SS) are significantly varied in different countries. We conducted the present study to survey the epidemiological characteristics of primary SS in China. We recruited 483 primary SS patients from 16 Chinese medical centers nationwide from January 2009 to November 2011 and assessed salivary and lacrimal gland dysfunction, organ involvement, and autoimmunity in these patients. The cohort included 456 women and 27 men (ratio, 17:1; mean age at onset, 42 ± 11 years; median age at diagnosis, 49 years; range, 41–56 years). Male patients showed a lower frequency of xerophthalmia (37.0% vs 60.7%) and a higher frequency of arthritis (40.7% vs 16.4%). Young-onset patients showed a higher frequency of low C3 levels (57.7% vs 36.3%) and pancytopenia (22.2% vs 8.8%). Patients with systemic involvement had a higher frequency of immunoglobulin A (IgA) (39.4% vs 22.5%) and immunoglobulin M (IgM) (12.4% vs 37.9%). Patients with pulmonary involvement had a higher parotid enlargement (21.4% vs 10.2%), purpura (12.1% vs 5.7%) and higher anti-La/SS-B (61.7% vs 41.8%), immunoglobulin G (IgG) (80.7% vs 64.6%) and IgA (48.9% vs 30.6%) levels. Patients with anti-Ro/SSA antibodies had more frequent exocrine gland symptoms and some extraglandular symptoms and immunological alterations. Compared with previous studies performed in other countries, SS patients in China showed particular clinical manifestation, systemic involvement, and immunological alterations. PMID:25906094

Tear clearance implications for ocular surface health.

PubMed

de Paiva, Cintia Sade; Pflugfelder, Stephen C

2004-03-01

Tear clearance/turnover provides a global assessment of the function of the lacrimal functional unit and of tear exchange on the ocular surface. It is an indirect measure of dry eye induced inflammation on the ocular surface. It shows better correlation with the severity of ocular irritation symptoms and corneal epithelial disease in dry eye than the Schirmer 1 test. Delayed tear clearance may prove to be the best measure for identifying patients with tear film disorders who may respond to anti-inflammatory therapy.

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes.

PubMed

Maciejczyk, Mateusz; Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian; Zalewska, Anna

2017-01-01

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands-nonstimulated and stimulated salivary flow, α -amylase, total protein-and salivary exoglycosidase activities-N-acetyl- β -hexosaminidase (HEX, HEX A, and HEX B), β -glucuronidase, α -fucosidase, β -galactosidase, and α -mannosidase-was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α -amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luijk, Peter van; Faber, Hette; Schippers, Jacobus M.

2009-07-15

Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) ofmore » both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation. Results: Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of 1 to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss. Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT.« less

Predictors of Silicone Tube Intubation Success in Patients with Lacrimal Drainage System Stenosis.

PubMed

Baek, Ji Sun; Lee, Saem; Lee, Jung Hye; Choi, Hye Sun; Jang, Jae Woo; Kim, Sung Joo

2016-06-01

To evaluate prognostic factors affecting silicone tube intubation outcomes in Asian patients with lacrimal drainage system stenosis. A retrospective review was conducted on the medical records of 822 patients (1,118 eyes) who had undergone silicone tube intubation to treat lacrimal drainage system stenosis between January 2011 and December 2012. Patients were divided into two groups: a success group and a failure group. Success was defined as the disappearance of epiphora symptoms, normalization of tear meniscus height, and the easy passage of fluid without resistance on the postoperative syringing test. Patient and ocular parameters were compared between the success and failure groups. A total of 994 eyes of 727 patients were included in analyses. Patients had a mean follow-up period of 34.11 ± 18.70 weeks. Silicone tube intubation was successful in 67.2% of participants. Significant differences between the success and failure groups were found for age (p < 0.001), history of ipsilateral facial palsy (p = 0.028), follow-up period (p < 0.001), and degree of passage on the preoperative syringing test (p = 0.001). Only age (p < 0.001) and degree of passage on the preoperative syringing test (p = 0.002) remained significantly associated with silicone tube intubation success in multivariate analysis. Age was negatively associated with silicone tube intubation success in patients with lacrimal drainage system stenosis. The success rate was higher in patients who showed easy passage of fluid without resistance on the preoperative syringing test. These factors should be considered by surgeons planning silicone tube intubation in patients with lacrimal drainage system stenosis.

[Functional morphology of the submandibular salivary glands of white rats during aging involution].

PubMed

Rybakova, M G

1979-12-01

Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function.

Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms.

PubMed

Jeong, Shin Young; Kim, Hae Won; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae

2013-05-01

Chronic sialadenitis is one of the most frequent chronic complications after radioactive iodine (RAI) therapy for thyroid cancer. To evaluate the long-term effects of RAI ablation on salivary gland function, we investigated scintigraphic changes in salivary glands by direct comparison of two salivary gland scintigraphies (SGSs) taken before and at 5 years after an RAI ablation. SGS was performed just before RAI ablation (pre-SGS) and ∼5 years after RAI ablation (F/U SGS) in 213 subjects who underwent thyroidectomy for thyroid cancer. The uptake score (U score) was graded, and the ejection fraction (EF) was quantified for the parotid and submandibular glands at pre-SGS and F/U SGS. Changes in salivary gland function were graded as mild, moderate, or severe according to the differences in U score and EF between the two SGSs. Xerostomia was assessed and compared with the SGS findings. Worsening of the U score was observed in 182 of 852 salivary glands (total: 21.3%; mild: 4.2%, moderate: 7.4%, severe: 9.7%), and 47.4% of the patients had a worsening U score for at least one of four salivary glands. A decrease in EF was observed in 173 of 852 salivary glands (total: 20.3%; mild: 5.4%, moderate: 6.8%, severe: 8.1%), and 43.7% of the patients experienced a decrease in the EF of at least one of the four salivary glands. Bilateral parotid gland dysfunction was the most commonly observed condition. Thirty-five (16.4%) patients complained of xerostomia at 5 years after RAI ablation. Scintigraphic changes in salivary gland function and xerostomia were more common in patients receiving 5.55 GBq, compared with 3.7 GBq. Xerostomia was more common in patients with submandibular gland dysfunction than those with parotid gland dysfunction (68.8% vs. 33.3%, p<0.05). The number of dysfunctional salivary glands was correlated with xerostomia (p<0.01). About 20% of the salivary glands were dysfunctional on SGS 5 years after a single RAI ablation, especially in patients who received higher doses of RAI. While parotid glands are more susceptible to (131)I-related damage, xerostomia was more associated with submandibular gland dysfunction and the prevalence of dysfunctional salivary glands.

Endoscopic-modified medial maxillectomy and its limitation for a solitary fibrous tumor of the lacrimal sac and nasolacrimal duct.

PubMed

Moriyama, Munehito; Kodama, Satoru; Hirano, Takashi; Suzuki, Masashi

2017-06-01

Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually arises from the pleura. Recently, SFTs have been reported in the head and neck region located in subsites such as the orbit. SFTs of the lacrimal sac are extremely rare, with only six cases reported in the English literature. We describe a SFT arising from the right lacrimal sac and extending along the nasolacrimal duct into the nasal cavity. Although, the tumor could not be removed by endoscopic-modified medial maxillectomy (EMMM) alone, combined approach with EMMM and a small external incision achieved the complete removal of the tumor. The patient has remained disease-free 24 months after surgery. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Paper-based surfaced enhanced Raman spectroscopy for drug level testing with tear fluid

NASA Astrophysics Data System (ADS)

Yamada, Kenji; Yokoyama, Moe; Jeong, Hieyong; Kido, Michiko; Ohno, Yuko

2015-07-01

The purpose of this study was to show the effectiveness of therapeutic drug level testing by Paper-based Surfaced Enhanced Raman Spectroscopy (PSERS) for artificial lacrimal fluid. We have been used substrates which consist of a common filter paper and gold nano-rods. The targets were Phenobarbital (PB) which dissolved in artificial lacrimal fluid. We measured them using PSERS which the wavelength was 785nm, the power was 30mW. It was found that there were the strong peaks of PB at 997cm-1 and 1026cm-1 which corresponded with solid PB spectral peak for 1mM artificial lacrimal fluid. The results demonstrated the usefulness of this method. It is concluded that our method for therapeutic drug level testing is very efficient.

Conjunctivodacryocystorhinostomy using a high-density porous polyethylene-coated tear drain tube.

PubMed

Pushker, Neelam; Khurana, Saurbhi; Shrey, Dinesh; Bajaj, Mandeep S; Chawla, Bhavna; Chandra, Mahesh

2013-08-01

To evaluate the outcome of conjunctivodacryocystorhinostomy using a high-density porous polyethylene (HDPP)-coated tear drain tube. Patients with epiphora due to a proximal lacrimal system block were included in a prospective interventional case study. A total of 22 eyes were treated with lacrimal bypass surgery using the HDPP-coated tube. On follow-up (12-41 months), 21 eyes had a patent well-positioned tube with subjective relief of epiphora. In one eye, a loose sleeve was noted during surgery. The tube dislodged postoperatively and was removed. A high success rate with only a few minor complications is achievable using a HDPP-coated tear drain tube for lacrimal bypass surgery. Long-term follow-up is required to look for tube blockage due to conjunctival or nasal mucosal overgrowth.

Immunohistochemical sweat gland profiles.

PubMed

Noël, Fanchon; Piérard, Gérald E; Delvenne, Philippe; Quatresooz, Pascale; Humbert, Philippe; Piérard-Franchimont, Claudine

2013-09-01

Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands. © 2013 Wiley Periodicals, Inc.

Central Connections of the Lacrimal Functional Unit.

PubMed

Willshire, Catherine; Buckley, Roger J; Bron, Anthony J

2017-08-01

To study the contribution of each eye to the reflex tear response, after unilateral and bilateral topical anesthesia. A closed-eye, modified Schirmer test was performed bilaterally in 8 normal subjects, in a controlled environment chamber set to 23°C, 45% relative humidity, and 0.08 m/s airflow. Eye drops were instilled into each eye 10 minutes before the Schirmer test. Experiments were as follows: 1) bilateral saline (control), 2) unilateral anesthesia (ipsilateral anesthetic; contralateral saline), and 3) bilateral anesthesia. There was no difference in between-eye wetting lengths in the saline control eyes (P = 0.394) or the bilaterally anesthetized eyes (P = 0.171). The wetting length was reduced in both eyes after bilateral anesthesia compared with saline controls (P = 0.001; P ≤ 0.0005). After unilateral anesthesia, the wetting length was reduced in the anesthetized eye compared with its saline control by 51.4% (P ≤ 0.0005) and compared with its fellow, unanesthetized eye (P = 0.005). The fellow eye value was also reduced compared with its saline control (P = 0.06). The wetting length was reduced by topical anesthesia, when instilled bilaterally and ipsilaterally. The latter response implies an ipsilateral, reflex sensory drive to lacrimal secretion. In the unanesthetized fellow eye, the reduction compared with its saline control was not quite significant. This implies a relative lack of central, sensory, reflex cross-innervation, although the possibility cannot entirely be ruled out. These results are relevant to the possibility of reflex lacrimal compensation from a normal fellow eye, in cases of unilateral corneal anesthesia.

Proteomic analysis in the Dufour's gland of Africanized Apis mellifera workers (Hymenoptera: Apidae).

PubMed

Teixeira, Aparecida das Dores; Games, Patricia D; Katz, Benjamin B; Tomich, John M; Zanuncio, José C; Serrão, José Eduardo

2017-01-01

The colony of eusocial bee Apis mellifera has a reproductive queen and sterile workers performing tasks such as brood care and foraging. Chemical communication plays a crucial role in the maintenance of sociability in bees with many compounds released by the exocrine glands. The Dufour's gland is a non-paired gland associated with the sting apparatus with important functions in the communication between members of the colony, releasing volatile chemicals that influence workers roles and tasks. However, the protein content in this gland is not well studied. This study identified differentially expressed proteins in the Dufour's glands of nurse and forager workers of A. mellifera through 2D-gel electrophoresis and mass spectrometry. A total of 131 spots showed different expression between nurse and forager bees, and 28 proteins were identified. The identified proteins were categorized into different functions groups including protein, carbohydrate, energy and lipid metabolisms, cytoskeleton-associated proteins, detoxification, homeostasis, cell communication, constitutive and allergen. This study provides new insights of the protein content in the Dufour's gland contributing to a more complete understanding of the biological functions of this gland in honeybees.

Impact of selective pituitary gland incision or resection on hormonal function after adenoma or cyst resection.

PubMed

Barkhoudarian, Garni; Cutler, Aaron R; Yost, Sam; Lobo, Bjorn; Eisenberg, Amalia; Kelly, Daniel F

2015-12-01

With the resection of pituitary lesions, the anterior pituitary gland often obstructs transsphenoidal access to the lesion. In such cases, a gland incision and/or partial gland resection may be required to obtain adequate exposure. We investigate this technique and determine the associated risk of post-operative hypopituitarism. All patients who underwent surgical resection of a pituitary adenoma or Rathke cleft cyst (RCC) between July 2007 and January 2013 were analyzed for pre- and post-operative hormone function. The cohort of patients with gland incision/resection were compared to a case-matched control cohort of pituitary surgery patients. Total hypophysectomy patients were excluded from outcome analysis. Of 372 operations over this period, an anterior pituitary gland incision or partial gland resection was performed in 79 cases (21.2 %). These include 53 gland incisions, 12 partial hemi-hypophysectomies and 14 resections of thinned/attenuated anterior gland. Diagnoses included 64 adenomas and 15 RCCs. New permanent hypopituitarism occurred in three patients (3.8 %), including permanent DI (3) and growth hormone deficiency (1). There was no significant difference in the rate of worsening gland dysfunction nor gain of function. Compared to a control cohort, there was a significantly lower incidence of transient DI (1.25 vs. 11.1 %, p = 0.009) but no significant difference in permanent DI (3.8 vs. 4.0 %) in the gland incision group. Selective gland incisions and gland resections were performed in over 20 % of our cases. This technique appears to minimize traction on compressed normal pituitary gland during removal of large lesions and facilitates better visualization and removal of cysts, microadenomas and macroadenomas.

Microbiology and Biofilm Trends of Silicone Lacrimal Implants: Comparing Infected Versus Routinely Removed Stents.

PubMed

Samimi, David B; Ediriwickrema, Lilangi S; Bielory, Brett P; Miller, Darlene; Lee, Wendy; Johnson, Thomas E

To investigate the pathogens and biofilms responsible for clinically significant infection of silicone stents implanted within the lacrimal system. Retrospective review of culture results and patient demographics for all silicone lacrimal stents removed early for clinically significant infection and sent to the Bascom Palmer Microbiology Laboratory through the end of year 2010. As a control, routinely removed, clinically noninfected stents from the same institution were prospectively sent for culture over a 6-month period. Four clinically infected and 6 clinically noninfected stents showing mucus within the lumen at removal were sent for scanning electron microscopy. Images were randomized and graded by a microbiologist for the presence of organisms, matrix deposits, organisms within matrix, and overall impression of significant biofilm formation. Nineteen stents were included in the study; 100% of clinically infected (n = 10) and noninfected (n = 9) stents were culture positive. Culture positivity for nontuberculous mycobacterium was found in 90% of infected stents and none of the noninfected stents (p < 0.001). Of infected stents, 50% grew Gram-positive organisms compared with 89% of noninfected stents (p = 0.07). Fifty percent of infected versus 67% of noninfected stents were culture positive for Gram-negative organisms (p = 0.46). Electron microscopy of stents revealed organisms consistent with culture results (size, shape) in planktonic and biofilm form. Masked observer image grading revealed a statistically significant higher amount of organism and biofilm on infected versus noninfected specimen. Nontuberculous mycobacteria comprise the primary pathogens responsible for clinically significant infection of silicone stents in the lacrimal system in South Florida. Robust biofilm production by this organism likely plays a role in pathogenesis. Further research into biofilm-related lacrimal implant infection may aid in the development of useful prevention and treatment strategies.

A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: Implications for future trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roesink, Judith M.; Schipper, Maria; Busschers, Wim

2005-11-15

Purpose: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. Methods and Materials: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H and N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion ofmore » radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. Results: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to {<=}25% of the preradiotherapy flow. Of all the subjective variables, only the single item dry mouth 6 weeks after radiotherapy was found to be significant. The best correlation with the mean parotid gland dose was found for the stimulated flow measurements. The predictive ability was the highest for the time point 1 year after radiotherapy. Subjective findings did not correlate with the mean parotid dose. Conclusions: Stimulated flow measurements using Lashley cups, with a complication defined as flow {<=}25% of the preradiotherapy output, correlated best with the mean parotid gland dose. When reduction of the mean dose to the parotid gland is intended, the stimulated flow measurement is the best method for evaluating parotid gland function.« less

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

PubMed Central

Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian

2017-01-01

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B), β-glucuronidase, α-fucosidase, β-galactosidase, and α-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands. PMID:29464184

Insulin-Like Growth Factor-1 Preserves Salivary Gland Function After Fractionated Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Limesand, Kirsten H., E-mail: limesank@u.arizona.ed; Department of Nutritional Sciences, University of Arizona, Tucson, AZ; Avila, Jennifer L.

Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVBmore » mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.« less

Opioid-Induced Hyperalgesia - Worsening Pain in Opioid-Dependent Patients

DTIC Science & Technology

2013-02-01

NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) United States Army Institute ofSurgical Research, JBSA Fort Sam Houston...distress and manifested no yawning, sweating, lacrimation , rhinorrhea, mydriasis, or piloerection. His abdomen was soft, nontender, and had a... functioning left lower quadrant colostomy with no signs of infection. He had bilateral AKAs without signs of infection. The remainder of the examination was

Human ocular anatomy.

PubMed

Kels, Barry D; Grzybowski, Andrzej; Grant-Kels, Jane M

2015-01-01

We review the normal anatomy of the human globe, eyelids, and lacrimal system. This contribution explores both the form and function of numerous anatomic features of the human ocular system, which are vital to a comprehensive understanding of the pathophysiology of many oculocutaneous diseases. The review concludes with a reference glossary of selective ophthalmologic terms that are relevant to a thorough understanding of many oculocutaneous disease processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: Comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muenter, Marc W.; Hoffner, Simone; Department of Nuclear Medicine, University of Heidelberg, Heidelberg

2007-03-01

Purpose: The aim of this study was to compare changes in salivary gland function after intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (RT), with or without Amifostine, for tumors of the head-and-neck region using quantitative salivary gland scintigraphy (QSGS). Methods and Materials: A total of 75 patients received pre- and post-therapeutic QSGS to quantify the salivary gland function. In all, 251 salivary glands were independently evaluated. Changes in the maximum uptake ({delta}U) and relative excretion rate ({delta}F) both pre- and post-RT were determined to characterize radiation-induced changes in the salivary gland function. In addition, dose-response curves were calculated. Results: In allmore » groups, maximum uptake and relative excretion rate were reduced after RT ({delta}U {<=}0 and {delta}F {<=}0). The reduction was significantly lower for IMRT than for conventional RT. For the parotid glands, the reduction was smaller for the IMRT-low than for the IMRT-high group. For the Amifostine-high and the conventional group the difference was significant only for one parameter ({delta}U, parotid and submandibular glands, p < 0.05). In contrast to this, the difference between the Amifostine-low and the conventional group was always significant or at least showed a clear trend for both changes in U and F. In regard to the endpoint 'reduction of the salivary gland excretion rate of more than 50%,' the dose-response curves yielded D{sub 50}-values of 34.2 {+-} 12.2 Gy for the conventionally treated group and 36.8 {+-} 2.9 Gy for the IMRT group. For the Amifostine group, an increased D{sub 50}-values of 46.3 {+-} 2.3 Gy was obtained. Conclusion: Intensity-modulated RT can significantly reduce the loss of parotid gland function when respecting a certain dose threshold. Conventional RT plus Amifostine prevents reduced salivary gland function only in the patient group treated with <40.6 Gy.« less

Endoscopic placement of Jones lacrimal tubes with the assistance of holmium YAG laser.

PubMed

Boboridis, Kostas G; Downes, Richard N

2005-06-01

The aim of this paper is to highlight the use of the Holmium YAG laser in the endoscopic placement of Lester Jones tubes in patients with a blocked canaliculus or failed lacrimal pump function. Sixteen cases with a non-functional canaliculus were included over a one-year period. Following caruncle excision, a 19 G needle is inserted through the medial canthal tissues into the nasal space. Nasal endoscopy confirms the accurate positioning in relation to the nasal anatomy. With the Holmium YAG laser, a tissue channel is fashioned around the guide needle through the structures of the lateral nasal wall to facilitate an accurate and secure placement of the Jones tube. The endoscopic, laser-assisted placement reduces the operating time to less than 20 minutes, minimizes tissue trauma and does not require the initial surgical steps of an open DCR procedure. There were 14 cases (87.5%) with securely retained tubes and two cases (12.5%) that required tube replacement. The advantage of the procedure is especially great in revision surgery where the ostium is opened through scar tissue. Nasal endoscopy with the assistance of the Holmium YAG laser offers simplicity and precision in the placement of Jones tubes. It minimizes tissue trauma and increases the surgical success rate.

Relation of sensory peripheral neuropathy in Sjögren syndrome to anti-Ro/SSA.

PubMed

Scofield, Amanda Kyle; Radfar, Lida; Ice, John A; Vista, Evan; Anaya, Juan-Manuel; Houston, Glen; Lewis, David; Stone, Donald U; Chodosh, James; Hefner, Kimberly; Lessard, Christopher J; Moser, Kathy L; Scofield, Robert Hal

2012-09-01

Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. Eight-eight patients attending a dry eyes-dry mouth clinic were diagnosed to have primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B(12) levels were determined using an enzyme-linked microtiter plate assay. Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception, or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (χ(2) = 8.46, P = 0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) had neuropathy (χ(2) = 5.587, P = 0.018, compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B(12) levels to neuropathy among these patients with Sjögren syndrome. Sensory peripheral neuropathy is common among patients with Sjögren syndrome and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion.

The cellular mechanisms of dry eye: from pathogenesis to treatment.

PubMed

Mantelli, Flavio; Massaro-Giordano, Mina; Macchi, Ilaria; Lambiase, Alessandro; Bonini, Stefano

2013-12-01

Dry eye is a complex disease characterized by changes in the ocular surface epithelia related to reduced quality and/or quantity of tears, inflammatory reaction, and impairment of ocular surface sensitivity. It has recently been proposed that increased tear osmolarity represents a main trigger to the altered cellular mechanisms leading to epithelial damage in dry eye. However, dry eye pathogenesis is multifactorial, with cytotoxic inflammatory mediators, altered lacrimal gland secretion and nerve function, squamous metaplasia of the conjunctival epithelium and decrease of goblet cells density, all playing a role in a detrimental loop that perpetuates and worsens damage to the corneal and conjunctival epithelia. Current topical treatments for dry eye patients include the use of lubricants and anti-inflammatory drugs. However, lubricants only improve symptoms temporarily, and chronic use of topical steroids is associated to severe ocular side effects such as cataract and glaucoma. The deeper understanding of the cellular mechanisms that are altered in dry eye is opening novel perspectives for patients and physicians, who are seeking treatments capable not only of improving symptoms but also of restoring the homeostasis of the ocular surface. In this review, we will focus on novel anti-inflammatory agents and on nerve growth factor, a neurotrophin that is altered in dry eye and has been suggested as a main player in the neuroimmune cross-talk of the ocular surface as well as in the stimulation of corneal sensitivity, epithelial proliferation and differentiation, and stimulation of mucin production by goblet cells. J. Cell. Physiol. 228: 2253-2256, 2013. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

Functional anatomy of the lacrimal gland in African black ostrich Struthio camelus domesticus in the embryonic and postnatal period.

PubMed

Klećkowska-Nawrot, Joanna; Goździewska-Harłajczuk, Karolina; Nowaczyk, Renata; Krasucki, Krzysztof

2015-03-25

The aim of the present study was morphological and histochemical analysis of the lacrimalgland (LG) in African black ostrich Struthio camelus domesticus in the embryonic and postnatalperiod. Studies were conducted on 50 ostriches aged between the 28th day of incubation until7 months old. Tissue sections were stained with haematoxylin and eosin, Azan trichrome,periodic acid-Schiff, Alcian blue pH 2.5, aldehyde fuchsin and Hale's dialysed iron. The LGin ostrich was classified as a tubulo-acinar type. The primordia of the lobes were determinedin the LG structure on the 28th day of incubation, whilst the weakly visible lobes with aciniand tubules were observed on the 40th day of incubation. Morphometric studies of the LGshowed steady growth, characterised by an increase in both length and width. Histometricmeasurements of lobe size showed little difference between the first, second and third agegroups, whilst in the fourth age group a marked increase in size of lobes was observed.The study showed that, apart from morphological changes, during the growth of the LGthe character of acid mucopolysaccharides changed. Sulphated acid mucopolysaccharideswere indicated, particularly with aldehyde fuchsin (AF) staining in the fourth age group.The Hale's dialysed iron (HDI) staining showed a low concentration of carboxylated acidmucopolysaccharides in the first and second age groups and a higher concentration in thethird and fourth age groups. Periodic acid-Schiff staining (PAS)-positive cells were observedin each age group, but only a small number of cells with a weakly PAS-positive reaction weredemonstrated in the first age group.

The clypeal gland: a new exocrine gland in termite imagoes (Isoptera: Serritermitidae, Rhinotermitidae, Termitidae).

PubMed

Křížková, Barbora; Bourguignon, Thomas; Vytisková, Blahoslava; Sobotník, Jan

2014-11-01

Social insects possess a rich set of exocrine organs producing diverse pheromones and defensive compounds. This is especially true for termite imagoes, which are equipped with several glands producing, among others, sex pheromones and defensive compounds protecting imagoes during the dispersal flight and colony foundation. Here, we describe the clypeal gland, a new termite exocrine organ occurring in the labro-clypeal region of imagoes of most Rhinotermitidae, Serritermitidae and Termitidae species. The clypeal gland of Coptotermes testaceus consists of class 1 (modified epidermal cell) and class 3 (bicellular gland unit) secretory cells. Ultrastructural features suggest that the gland secretes volatile compounds and proteins, probably after starting the reproduction. One peculiar feature of the gland is the presence of multiple secretory canals in a single canal cell, a feature never observed before in other insect glands. Although the function of the gland remains unknown, we hypothesize that it could produce secretion signalling the presence of functional reproductives or their need to be fed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Proteomic analysis in the Dufour’s gland of Africanized Apis mellifera workers (Hymenoptera: Apidae)

PubMed Central

2017-01-01

The colony of eusocial bee Apis mellifera has a reproductive queen and sterile workers performing tasks such as brood care and foraging. Chemical communication plays a crucial role in the maintenance of sociability in bees with many compounds released by the exocrine glands. The Dufour’s gland is a non-paired gland associated with the sting apparatus with important functions in the communication between members of the colony, releasing volatile chemicals that influence workers roles and tasks. However, the protein content in this gland is not well studied. This study identified differentially expressed proteins in the Dufour’s glands of nurse and forager workers of A. mellifera through 2D-gel electrophoresis and mass spectrometry. A total of 131 spots showed different expression between nurse and forager bees, and 28 proteins were identified. The identified proteins were categorized into different functions groups including protein, carbohydrate, energy and lipid metabolisms, cytoskeleton-associated proteins, detoxification, homeostasis, cell communication, constitutive and allergen. This study provides new insights of the protein content in the Dufour’s gland contributing to a more complete understanding of the biological functions of this gland in honeybees. PMID:28542566

Histologic characteristics and local cellular immunity of the gland of the third eyelid after topical ophthalmic administration of 2% cyclosporine for treatment of dogs with keratoconjunctivitis sicca.

PubMed

Izci, Celal; Celik, Ilhami; Alkan, Fahrettin; Ogurtan, Zeki; Ceylan, Cengiz; Sur, Emrah; Ozkan, Yasemin

2002-05-01

To evaluate the efficacy of topical administration of a 2% solution of cyclosporine (CsA) for treatment of dogs with keratoconjunctivitis sicca (KCS) and to correlate results with histopathologic characteristics and local cellular immunity of the gland of the third eyelid. 24 dogs with bilateral KCS. Lacrimal secretion was measured, using Schirmer tear test (STT) strips. Leukocyte and T-lymphocyte subsets were determined in blood samples. Histopathologic changes as well as CD4+, CD8+, and alpha-naphthyl-acetate esterase-positive (ANAE+) lymphocytes were evaluated. Clinical signs resolved at the end of 1 month in conjunction with significantly increased STT values, compared with baseline values. Fifteen and 30 days after discontinuation of CsA treatment, a decrease was observed in STT values in both eyes; however, only values for the right eye were significantly different. There was a significant decrease in the number of lymphocytes and ANAE+ lymphocytes 15 and 30 days after discontinuation of CsA treatment, compared with baseline values. Differences were not observed in number of CD4+ lymphocytes among treatment groups. However, there was a significant decrease in number of CD8+ lymphocytes with reversal of the CD4+:CD8+ in both eyes after CsA treatment for 30 days, compared with the control group. Increased secretory activity and decreased lymphocyte infiltration were characteristic histopathologic findings. Topical administration of a 2% solution of CsA was effective for the treatment of dogs with KCS. Strict follow-up monitoring is required after the cessation of treatment because of the possibility of recurrence of KCS.

Riedel's thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum.

PubMed

Dahlgren, Mollie; Khosroshahi, Arezou; Nielsen, G Petur; Deshpande, Vikram; Stone, John H

2010-09-01

Riedel's thyroiditis is a chronic fibrosing disorder of unknown etiology often associated with "multifocal fibrosclerosis." IgG4-related systemic disease is characterized by IgG4+ plasma cell infiltration and fibrosis throughout many organs. We hypothesized that Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. We searched our institution's pathology database using the terms "Riedel's," "struma," "thyroid," and "fibrosis," and identified 3 cases of Riedel's thyroiditis. Riedel's thyroiditis was diagnosed if there was a fibroinflammatory process involving all or a portion of the thyroid gland, with evidence of extension of the process into surrounding tissues. Immunohistochemical stains for IgG4 and IgG were performed. The histopathologic and immunohistochemical features of each involved organ were evaluated. The clinical features of one patient with multiple organ system disease were described. All 3 thyroidectomy samples stained positively for IgG4-bearing plasma cells. One patient had extensive extrathyroidal involvement diagnostic of IgG4-related systemic disease, including cholangitis, pseudotumors of both the lung and lacrimal gland, and a lymph node contiguous to the thyroid that stained intensely for IgG4+ plasma cells. The histologic features of all organs involved were consistent with IgG4-related systemic disease. Patient 3 had 10 IgG4+ plasma cells per high-power field initially, but rebiopsy 2 years later demonstrated no IgG4+ plasma cells. That patient's second biopsy, characterized by fibrosis and minimal residual inflammation, further solidifies the link between IgG4-bearing plasma cells in tissue and the histologic evolution to Riedel's thyroiditis. Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. In many cases, multifocal fibrosclerosis and IgG4-related systemic disease are probably the same entity.

A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

PubMed

Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

2016-01-01

Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

PubMed Central

Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

2016-01-01

Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4–8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer’s patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

Autoantibodies against Muscarinic Type 3 Receptor in Sjögren's Syndrome Inhibit Aquaporin 5 Trafficking

PubMed Central

Lee, Byung Ha; Gauna, Adrienne E.; Perez, Geidys; Park, Yun-jong; Pauley, Kaleb M.; Kawai, Toshihisa; Cha, Seunghee

2013-01-01

Sjögren's syndrome (SjS) is a chronic autoimmune disease that mainly targets the salivary and lacrimal glands. It has been controversial whether anti-muscarinic type 3 receptor (α-M3R) autoantibodies in patients with SjS inhibit intracellular trafficking of aquaporin-5 (AQP5), water transport protein, leading to secretory dysfunction. To address this issue, GFP-tagged human AQP5 was overexpressed in human salivary gland cells (HSG-hAQP5) and monitored AQP5 trafficking to the plasma membrane following carbachol (CCh, M3R agonist) stimulation. AQP5 trafficking was indeed mediated by M3R stimulation, shown in partial blockage of trafficking by M3R-antagonist 4-DAMP. HSG-hAQP5 pre-incubated with SjS plasma for 24 hours significantly reduced AQP5 trafficking with CCh, compared with HSG-hAQP5 pre-incubated with healthy control (HC) plasma. This inhibition was confirmed by monoclonal α-M3R antibody and pre-absorbed plasma. Interestingly, HSG-hAQP5 pre-incubated with SjS plasma showed no change in cell volume, compared to the cells incubated with HC plasma showing shrinkage by twenty percent after CCh-stimulation. Our findings clearly indicate that binding of anti-M3R autoantibodies to the receptor, which was verified by immunoprecipitation, suppresses AQP5 trafficking to the membrane and contribute to impaired fluid secretion in SjS. Our current study urges further investigations of clinical associations between SjS symptoms, such as degree of secretory dysfunction, cognitive impairment, and/or bladder irritation, and different profiles (titers, isotypes, and/or specificity) of anti-M3R autoantibodies in individuals with SjS. PMID:23382834

Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren’s Syndrome According to Ancestry

PubMed Central

Taylor, Kimberly E.; Wong, Quenna; Levine, David M.; McHugh, Caitlin; Laurie, Cathy; Doheny, Kimberly; Lam, Mi Y.; Baer, Alan N.; Challacombe, Stephen; Lanfranchi, Hector; Schiødt, Morten; Srinivasan, M.; Umehara, Hisanori; Vivino, Frederick B.; Zhao, Yan; Shiboski, Stephen; Daniels, Troy E.; Greenspan, John S.; Shiboski, Caroline H.; Criswell, Lindsey A.

2017-01-01

Objective Sjögren's Syndrome (SS) is a systemic autoimmune disease affecting primarily the lacrimal and salivary glands. The Sjögren's International Collaborative Clinical Alliance (SICCA) is an international multisite observational study whose participants have been genotyped on the Omni 2.5M platform and undergone deep phenotyping using common protocol-directed methods, providing a unique opportunity to examine the genetic etiology of SS across ancestry and disease subsets. Methods We perform GWAS analyses utilizing dbGaP controls on all subjects (1405 cases, 1622 SICCA controls, 3125 external controls), European (similarly 585, 966, 2580), and Asian (similarly 460, 224, 901) with ancestry adjustments via principal component analyses. We also investigate whether subphenotype distributions differ by ethnicity and if this contributes to heterogeneity of genetic associations. Results We see significant associations in established regions of the MHC, IRF5, and STAT4 (p=3e-42, p=3e-14, p=9e-10, respectively), and several suggestive novel regions (2 or more associations with p<1e-5). Two regions have been previously implicated in autoimmune disease: KLRG1 (p=6e-7, Asian) and SH2D2A (p=2e-6, all). We observe striking differences between the European and Asian associations, with high heterogeneity especially in the MHC; representative SNPs from established and suggestive regions have highly significant differences in population allele frequencies. We show that SSA/SSB autoantibody production and labial salivary gland Focus Score criteria are associated with higher non-European ancestry (p=4e-15, 4e-5, respectively), but that subphenotype differences do not explain most of the ancestry differences in genetic associations. Conclusion Genetic associations with SS differ markedly by ancestry, however this is not explained by differences in subphenotypes. PMID:28076899

Cardiobacterium hominis-induced acute dacryocystitis and lacrimal abscess

PubMed Central

Manderwad, Guru Prasad; Kodiganti, Manjulatha; Ali, Mohammad Javed

2014-01-01

Cardiobacterium hominis is a member of the HACEK (Haemophilus sp., Actinobacillus actinomycetemcomitans, C. hominis, Eikenella corrodens, and Kingella kingae) group commonly associated with endocarditits and is normally present in the respiratory tract. We describe the first case of acute dacryocystitis with lacrimal abscess caused by C. hominis along with a brief review of the literature. The patient responded to oral and topical ciprofloxacin after incision and drainage and awaits dacryocystorhinostomy. PMID:24008805

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function.

PubMed

Nam, Kihoon; Maruyama, Christina L; Wang, Ching-Shuen; Trump, Bryan G; Lei, Pedro; Andreadis, Stelios T; Baker, Olga J

2017-01-01

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration.

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function

PubMed Central

Nam, Kihoon; Maruyama, Christina L.; Wang, Ching-Shuen; Trump, Bryan G.; Lei, Pedro; Andreadis, Stelios T.

2017-01-01

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration. PMID:29095857

Parathyroid-specific interaction of the calcium-sensing receptor and Gaq

PubMed Central

Pi, Min; Chen, Ling; Huang, MinZhao; Luo, Qiang; Quarles, L. Darryl

2009-01-01

The calcium-sensing receptor regulates various parathyroid gland functions, including hormone secretion, gene transcription, and chief cell hyperplasia through Gαq- and Gαi-dependent signaling pathways. To determine the specific function of Gαq in these processes, we generated transgenic mice using the human parathyroid hormone promoter to drive overexpression of a dominant negative Gαqloop minigene to selectively disrupt Gαq function in the parathyroid gland. The Gαqloop mRNA was highly expressed in the parathyroid gland but not in other tissues of these transgenic mice. Gross appearance, body weight, bone mineral density, and survival of the transgenic mice were indistinguishable from those of their wild-type littermates. Adult transgenic mice, however, exhibited an increase in parathyroid hormone mRNA and in its basal serum level as well as in gland size. The response of the parathyroid gland to hypocalcemia was found to be reduced in sensitivity in the transgenic mice when compared to their wild-type controls. Abnormalities of the parathyroid gland function in these transgenic mice were similar to those of heterozygous Gαq+/− and calcium sensing receptor+/− mice. These studies demonstrate the feasibility of selectively targeting the parathyroid gland to investigate signaling mechanisms downstream of the calcium receptor. PMID:18813283

Functional salivary gland regeneration by transplantation of a bioengineered organ germ

PubMed Central

Ogawa, Miho; Oshima, Masamitsu; Imamura, Aya; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Nakajima, Kei; Hirayama, Masatoshi; Tachikawa, Tetsuhiko; Tsuji, Takashi

2013-01-01

Salivary gland hypofunction, also known as xerostomia, occurs as a result of radiation therapy for head cancer, Sjögren’s syndrome or aging, and can cause a variety of critical oral health issues, including dental decay, bacterial infection, mastication dysfunction, swallowing dysfunction and reduced quality of life. Here we demonstrate the full functional regeneration of a salivary gland that reproduces the morphogenesis induced by reciprocal epithelial and mesenchymal interactions through the orthotopic transplantation of a bioengineered salivary gland germ as a regenerative organ replacement therapy. The bioengineered germ develops into a mature gland through acinar formations with a myoepithelium and innervation. The bioengineered submandibular gland produces saliva in response to the administration of pilocarpine and gustatory stimulation by citrate, protects against oral bacterial infection and restores normal swallowing in a salivary gland-defective mouse model. This study thus provides a proof-of-concept for bioengineered salivary gland regeneration as a potential treatment of xerostomia. PMID:24084982

Microvascular transplantation and replantation of the dog submandibular gland.

PubMed

Su, Wan Fu; Jen, Yee Min; Chen, Shyi Gen; Nieh, Shin; Wang, Chih-Hung

2006-05-01

Transplantation and replantation of the submandibular gland with microvascular techniques were demonstrated in a previous study, with good gland survival. The application of radiation on the neck bed was attempted to address an actual clinical scenario in this study. Five canine submandibular glands were transplanted using microvascular techniques to the ipsilateral femoral system. Radiotherapy at a dosage level of 3,600 cGy using 600 cGy q.d was delivered to the nasopharyngeal and neck regions 2 weeks after transplantation. The transferred glands were then reintroduced into the original but radiated neck bed. The glands were harvested for histological examination 8 weeks later. Four of five canine submandibular glands can withstand microvascular transplantation and then replantation into a radiated neck bed for at least 8 weeks. However, the salivary function was depleted. The canine submandibular gland can survive the transplantation and replantation for at least 8 weeks in spite of precipitating radiation insult on the neck bed for 3 weeks. Neurorraphy is, however, essential to maintaining the glandular function.

Videoreflective dacryomeniscometry in normal adults and in patients with functional or primary acquired nasolacrimal duct obstruction.

PubMed

Francis, Ian C; Chan, Derek G; Papalkar, Daya; Papas, Eric B; Stapleton, Fiona

2005-03-01

Videoreflective dacryomeniscometry (VRD) for evaluation of marginal tear film has not been performed in patients with watery eye or in a controlled study. We used VRD to evaluate the height of the central marginal lower lid tear film in normal adults and compared it with two watery-eye groups and a postoperative dacryocystorhinostomy (DCR) group. Case-controlled interventional case series. We evaluated with VRD 20 subjects with normal lacrimal drainage function, 21 patients with primary acquired nasolacrimal duct obstruction (PANDO), 28 patients with functional nasolacrimal duct obstruction (FNLDO), and a postoperative group of 14 patients derived from the previous two pathologic groups. Comparison between the four groups was performed to determine statistically significant differences between tear film height. PANDO and FNLDO groups were shown to have significantly greater median tear meniscus heights ([TMH] PANDO: 620 microm, interquartile range [IQR] 453 microm; FNLDO: 731 microm, IQR 529 microm) than normal subjects (296 microm, IQR 214 microm; P < .001) and postoperative PANDO patients (265 microm, IQR 159 microm). There was no significant difference in TMH between PANDO and FNLDO groups preoperatively (P = .275). There was a reduction in median TMH postoperatively of 355 microm (P = .008) in PANDO and 360 microm (P = .068) in FNLDO. PANDO and FNLDO patients have similar preoperative TMH. In both these groups, TMH is significantly greater than in normal control subjects. Lacrimal drainage surgery substantially reduces TMH as measured using VRD in PANDO.

Human Parotid Gland Alpha-Amylase Secretion as a Function of Chronic Hyperbaric Exposure

DTIC Science & Technology

1979-01-01

parotid ...Pullman, WA 99163 Gilman, S. C, G. J. Fischer, R. J. Biersner, R. D. Thornton, and D. A. Miller. 1979. Human parotid gland alpha-amylase secretion...as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 6(3):303-307.—Secretion of a-amylase by the human parotid gland increased

Reproductive biology in Anophelinae mosquitoes (Diptera, Culicidae): Fine structure of the female accessory gland.

PubMed

Laghezza Masci, Valentina; Di Luca, Marco; Gambellini, Gabriella; Taddei, Anna Rita; Belardinelli, Maria Cristina; Guerra, Laura; Mazzini, Massimo; Fausto, Anna Maria

2015-07-01

The morphology and ultrastructure of female accessory reproductive glands of Anopheles maculipennis s.s., Anopheles labranchiae and Anopheles stephensi were investigated by light and electron microscopy. The reproductive system in these species is characterized by two ovaries, two lateral oviducts, a single spermatheca and a single accessory gland. The gland is globular and has a thin duct which empties into the vagina, near the opening of the spermathecal duct. Significant growth of the accessory reproductive gland is observed immediately after blood meal, but not at subsequent digestion steps. At ultrastructural level, the gland consists of functional glandular units belonging to type 3 ectodermal glands. The secretory cells are elongated and goblet shaped, with most of their cytoplasm and large nucleus in the basal part, close to the basement lamella. Finely fibrous electron-transparent material occupies the secretory cavity that is in contact with the end of a short efferent duct (ductule) emerging from the gland duct. The present study is the first detailed description of female accessory gland ultrastructure in Anophelinae and provides insights into the gland's functional role in the reproductive biology of these insects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

ClinicalTrials.gov

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

Determination of loss tangent of human tear film at 9.8 GHz

NASA Astrophysics Data System (ADS)

Bansal, Namita; Dhaliwal, A. S.; Mann, K. S.

2015-08-01

Basal (non-stimulated) tears that are produced by accessory lacrimal glands located in conjunctiva of human eye, form tear film which in turn keeps the eye moist and lubricate; nourishes the eye; protects the eye from dust, bacterial infection and shear forces generated during eye movements and blinking; and provides a refractive surface on the corneal epithelium. Film is known to contain water, mucin, lipids, lysozyme, glucose, urea, sodium etc. In present communication, loss tangent of human tear film has been determined at 9.8 GHz microwaves by employing cavity perturbation technique at a temperature of 37°C. The basal tears from a small population comprising six subjects were collected and average value of loss tangent is reported. Slater's technique was used to reduce the error caused in measuring the volume of sample. The determined values are useful to study the biological effects of microwaves on tear film as well as other parts of human eye such as eye lens and lens epithelial cells. To the best of author's knowledge, no such study is available in literature at any radio as well as microwave frequencies; therefore present determinations are first of its kind.

Investigational drugs in dry eye disease.

PubMed

Nebbioso, Marcella; Fameli, Valeria; Gharbiya, Magda; Sacchetti, Marta; Zicari, Anna Maria; Lambiase, Alessandro

2016-12-01

The dry eye disease (DED) is a chronic multifactorial disorder of the tears that also involves the ocular surface, the lacrimal glands, and meibomian dysfunction. Furthermore, DED is often associated with Sjögren's syndrome (SS) and other autoimmune disorders. Sometimes, this chronic or subclinical condition is difficult to diagnose and treat, due to its heterogeneity. Areas covered: A literature search of relevant publications about treatment of DED was performed. All relevant articles published between 2011 and 2016 were identified through a computerized search for reviews and clinical trials using the Pub Med database. In particular, investigational treatments have been reported in this peer-reviewed publication. Relevant articles identified were manually searched and reviewed, then data concerning with novel treatment for DED were included into the manuscript. Expert opinion: The treatment of dry eye patients evolves continuously because DED seriously impacts the quality of life of older adults. Indeed, as a chronic disease, DED prevalence is expected to worsen with the aging population. For this reason, current efforts focus on combined pharmacological strategies targeted towards multiple systems. Probably this is the correct way to reach a long lasting symptoms relief treatment that may allow an actual improvement of patients' quality of life.

Extrapulmonary sites of radiogallium accumulation in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sulavik, S.B.; Palestro, C.J.; Spencer, R.P.

1990-12-01

In an effort to detect extrapulmonary sites of radiogallium accumulation in cases of sarcoidosis, 145 separate Ga-67 citrate studies of 114 patients with biopsy-proven sarcoidosis were examined. The most characteristic extrapulmonary radiogallium uptake pattern was the panda sign in 47 patients (41%). The most common site of prominent extrapulmonary radiogallium uptake was the lacrimal glands in 101 patients (88%). Second most common was activity in one or more superficial lymph node regions such as the cervical, axillary, femoral, or inguinal in 19 patients (17%). Other extrapulmonary sites included breast uptake in 6 out of 80 women (8%), prominent splenic andmore » nasal uptake in 9 (8%) patients, periportal accumulation in 7 (6%), and cutaneous/subcutaneous activity in 4 (4%). Because many of these individuals were receiving corticosteroids, the natural (untreated) prevalence of extrapulmonary findings may be even higher. Although the sensitivity and specificity of extrapulmonary radiogallium accumulation has still to be determined, many of the sites may be accessible to biopsy both for diagnostic purposes and to follow the effects of medications. It is therefore suggested that whole-body imaging be performed when radiogallium is administered to patients with suspected or known sarcoidosis.« less

Significance of mucin on the ocular surface.

PubMed

Watanabe, Hitoshi

2002-03-01

To review the significance of mucin in the tear film and the ocular surface epithelium. Summary of the information on how mucin derived from the corneal and conjunctival epithelia and from goblet cells plays a role in the stability of the tear film over the ocular surface. The change in mucin expression derived from the ocular surface epithelium is also discussed with reference to ocular surface disease. The corneal and conjunctival epithelia produce transmembrane mucins such as MUC1, MUC2, and MUC4. In contrast, goblet cells produce the gel-forming secretory mucin, MUC5AC. The lacrimal gland produces MUC7. On the ocular surface, cooperation between transmembrane mucin and secretory mucin is necessary for the stability of the tear film. The expression of mucin from the ocular surface epithelium is coordinated from the time of eyelid opening and is altered in conditions such as squamous metaplasia and dry eye. This alteration may result in instability of the tear film. CONCLU SION: The induction of mucin from the ocular surface may facilitate the stability of the tear film, and increased knowledge may lead to the development of a new modality for the treatment of dry eye.

Sparing the region of the salivary gland containing stem cells preserves saliva production after radiotherapy for head and neck cancer

PubMed Central

van Luijk, Peter; Pringle, Sarah; Deasy, Joseph O.; Moiseenko, Vitali V.; Faber, Hette; Hovan, Allan; Baanstra, Mirjam; van der Laan, Hans P.; Kierkels, Roel G. J.; van der Schaaf, Arjen; Witjes, Max J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Wu, Jonn; Coppes, Robert P.

2016-01-01

Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia. PMID:26378247

Endocanalicular diode laser dacryocystorhinostomy for nasolacrimal duct obstruction: short-term results of a new minimally invasive surgical technique.

PubMed

Özçimen, Muammer; Uysal, Ismail Onder; Eryılmaz, Mehmet Akif; Kal, Ali

2010-11-01

To evaluate the results, complications, effectiveness, and operative results of the endocanalicular laser dacryocystorhinostomy (ECL DCR) in the distal obstructions of the lacrimal drainage system. Sixty eyes of 57 patients who had a diagnosis of distal obstruction of the lacrimal drainage system were evaluated retrospectively in this study. All patients underwent ECL DCR by diode laser between October 2008 and July 2009. Forty-nine patients (86%) were females, 8 patients (14%) were males, and age distribution was between 3 and 84 years old (median, 40 y). The canaliculi were intubated by a silicone tube. The patency of the nasolacrimal system was controlled by lacrimal lavage, loss of epiphora, and endoscopic evaluation of the endonasal rhinostomy site with routine follow-up scheduled at first day and 1-week, 1-month, and 3-month postoperative intervals. After the 60 ECL DCRs, 10 patients underwent revision ECL DCR because of the persistent epiphora. The patency of the nasolacrimal duct or the decrease of the symptoms was assigned as success. There were no symptoms at all in 83.3% of the patients. The ECL DCR in the treatment of the distal obstructions of the lacrimal drainage system was easily tolerated by the patients, cosmetically preferred because there was no incision and scar formation with high success rates, and a minimally invasive alternative technique.

Comparison of post-surgical MRI presentation of the pituitary gland and its hormonal function.

PubMed

Bladowska, Joanna; Sokolska, Violetta; Sozański, Tomasz; Bednarek-Tupikowska, Grażyna; Sąsiadek, Marek

2010-01-01

Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change of anatomical conditions. It depends also on numerous other factors, including: size and expansion of a tumour before surgery, type of surgical access, quality and volume of filling material used and time of its resorption.The aim of the study was to compare MR image of the pituitary gland after surgery with clinical findings and to establish a correlation between MRI presentation of spared pituitary and its hormonal function. 124 patients after resection of pituitary adenomas - 409 MRI results in total - were studied. With a 1.5-T unit, T1-weighted sagittal and coronal, enhanced and unenhanced images were obtained. The pituitary gland seemed to be normal in MRI in 11 patients, 8 of them had completely regular pituitary function but in 3 of them we noticed a partial hypopituitarism. In 99 patients only a part of the pituitary gland was recognised, 53 of them had hypopituitarism but 46 of them were endocrinologically healthy. 14 patients seemed to have no persistent pituitary gland in MRI, in comparison to hormonal studies: there was panhypopituitarism in 6 and hypopituitarism in 8 cases. MRI presentation of post - surgical pituitary gland doesn't necessarily correlate with its hormonal function - there was a significant statistical difference. Some patients with partial pituitary seems normal hormonal function. In some cases the pituitary seem normal in MRI but these patients have hormonal disorders and need substitution therapy.

Clinical and Molecular Inflammatory Response in Sjögren Syndrome-Associated Dry Eye Patients Under Desiccating Stress.

PubMed

López-Miguel, Alberto; Tesón, Marisa; Martín-Montañez, Vicente; Enríquez-de-Salamanca, Amalia; Stern, Michael E; González-García, María J; Calonge, Margarita

2016-01-01

To evaluate the response of the lacrimal function unit in Sjögren syndrome (SS)-associated dry eye patients exposed to 2 simulated daily life environmental conditions. Prospective crossover pilot study. Fourteen female SS dry eye patients were exposed for 2 hours to a controlled normal condition (23 C, 45% relative humidity, and air flow 0.10 m/s) and a controlled adverse condition that simulates desiccating stress (23 C, 5% relative humidity, and air flow 0.10 m/s). The following dry eye tests were performed before and after the exposure: tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear break-up time, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test. Levels of 16 molecules were analyzed in tears by multiplex immunobead analysis. Clinical evaluation showed lacrimal functional unit impairment after the desiccating stress: significantly increased tear osmolarity (315.7 ± 3.0 vs 327.7 ± 5.1 mOsm/L, P = .03), conjunctival hyperemia (1.3 ± 0.1 vs 1.6 ± 0.1, P = .05), and corneal staining in temporal (3.5 ± 0.5 vs 4.7 ± 0.4, P = .01) and nasal (3.6 ± 0.5 vs 4.5 ± 0.5, P = .04) areas. Tear concentrations increased for interleukin-1 receptor antagonist (16 557.1 ± 4047.8 vs 31 895.3 ± 5916.5 pg/mL, P = .01), interleukin-6 (63.8 ± 20.2 vs 111.5 ± 29.6 pg/mL, P = .02), interleukin-8 (2196.1 ± 737.9 vs 3753.2 ± 1106.0 pg/mL, P = .03), and matrix metalloproteinase-9 (101 515.6 ± 37 088.4 vs 145 867.1 ± 41 651.5 pg/mL, P = .03). After the simulated normal condition, only a significant increase in nasal corneal staining (2.9 ± 0.5 vs 3.6 ± 0.5, P = .03) was observed. Even a short exposure to a desiccating environment can produce a significant deterioration of the lacrimal function unit in female SS dry eye patients. The often unnoticed exposure to these conditions during daily life may increase inflammatory activity rapidly, triggering an ocular surface deterioration. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effect of pineal gland peptides on morphofunctional structure of the pancreas in ageing].

PubMed

Ryzhak, A P; Kostiuchek, I N; Kvetnoĭ, I M

2007-01-01

A study of pineal gland peptides effect on morphology and functions of the pancreas in the model of premature ageing in rats was performed with respect to the need in methods for premature ageing prevention. Structural, morphological and functional alterations in pancreas tissue, suggesting premature ageing of the gland, were identified by methods of immunohistochemistry and electronic microscopy. There was registered a geroprotective effect of the pineal gland peptides on pancreas tissue, manifested in the resistance of the latter to the impact of stress factors entailing premature ageing.

The natural process of congenital nasolacrimal duct obstruction and effect of lacrimal sac massage.

PubMed

Karti, Omer; Karahan, Eyyup; Acan, Durgul; Kusbeci, Tuncay

2016-12-01

This study aimed to examine the rate of symptomatic improvement of congenital nasolacrimal duct obstruction (CNLDO) in infants treated with conservative management within the first year of age. Other purpose of the study is to emphasize the relationship between spontaneous resolution time and effective lacrimal sac massage. Thirty-one infants were diagnosed to have CNLDO by an ophthalmologist prior to 3 months of age. In this study, 36 eyes of 31 patients were included with CNLDO. The patients were divided into two groups. Group 1 (28 eyes of 24 patients) was consisted of the patients who were applied effective lacrimal sac massage regularly during the follow-up period, and patients whose parents did not apply a regular lacrimal passage regularly were accepted as group 2 (8 eyes of 7 patients). Thirty-three eyes of 31 patients (18 rights and 15 left) successfully resolved with only conservative management (91.6 %). In these thirty-three eyes, one eye (3 %) resolved between 0 and 3 months, fourteen eyes (42.5 %) resolved between 4 and 6 months, eleven eyes (33.3 %) resolved between 7 and 9 months, and seven eyes (21.2 %) resolved between 10 and 12 months. CNLDO was resolved in 27 (96.2 %) of 28 eyes in group 1, and in group 2, six eyes (77.7 %) had resolvement. This difference was statistically significant (p = 0.001). The mean age of resolution was 6.8 ± 1.88 months in group 1, 10.3 ± 1.5 months in group 2 (p < 0.001). In light of our study, we believe that conservative management of CNLDO is highly successful. Our study provided a possible objective explanation for the efficacy of lacrimal sac massage. Emphasizing the importance of the massage to parents and describing in detail can reduce the risk of unnecessary surgical interventions.

A Multidisciplinary Orbit-Sparing Treatment Approach That Includes Proton Therapy for Epithelial Tumors of the Orbit and Ocular Adnexa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holliday, Emma B.; Esmaeli, Bita; Pinckard, Jamie

Purpose: Postoperative radiation is often indicated in the treatment of malignant epithelial tumors of the orbit and ocular adnexa. We present details of radiation technique and toxicity data after orbit-sparing surgery followed by adjuvant proton radiation therapy. Methods and Materials: Twenty patients underwent orbit-sparing surgery followed by proton therapy for newly diagnosed malignant epithelial tumors of the lacrimal gland (n=7), lacrimal sac/nasolacrimal duct (n=10), or eyelid (n=3). Tumor characteristics, treatment details, and visual outcomes were obtained from medical records. Acute and chronic toxicity were prospectively scored using Common Terminology Criteria for Adverse Events version 4.0. Results: The median radiation dosemore » was 60 Gy(RBE) (relative biological effectiveness; [range 50-70 Gy]); 11 patients received concurrent chemotherapy. Dose to ipsilateral anterior optic structures was reduced in 13 patients by having them gaze away from the target during treatment. At a median follow-up time of 27.1 months (range 2.6-77.2 months), no patient had experienced local recurrence; 1 had regional and 1 had distant recurrence. Three patients developed chronic grade 3 epiphora, and 3 developed grade 3 exposure keratopathy. Four patients experienced a decrease in visual acuity from baseline but maintained vision sufficient to perform all activities of daily living without difficulty. Patients with grade ≥3 chronic ocular toxicity had higher maximum dose to the ipsilateral cornea (median 46.3 Gy[RBE], range 36.6-52.7 Gy[RBE] vs median 37.4 Gy[RBE], range 9.0-47.3 Gy(RBE); P=.017). Conclusions: Orbit-sparing surgery for epithelial tumors of the orbit and ocular adnexa followed by proton therapy successfully achieved disease control and was well tolerated. No patient required orbital exenteration or enucleation. Chronic grade 3 toxicity was associated with high maximum dose to the cornea. An eye-deviation technique can be used to limit the maximum corneal dose to <35 Gy(RBE).« less

Sweat, the driving force behind normal skin: an emerging perspective on functional biology and regulatory mechanisms.

PubMed

Murota, Hiroyuki; Matsui, Saki; Ono, Emi; Kijima, Akiko; Kikuta, Junichi; Ishii, Masaru; Katayama, Ichiro

2015-01-01

The various symptoms associated with excessive or insufficient perspiration can significantly reduce a patient's quality of life. If a versatile and minimally invasive method could be established for returning sweat activity to normalcy, there is no question that it could be used in the treatment of many diseases that are believed to involve perspiration. For this reason, based on an understanding of the sweat-gland control function and sweat activity, it was necessary to conduct a comprehensive search for the factors that control sweating, such as the central and peripheral nerves that control sweat-gland function, the microenvironment surrounding the sweat glands, and lifestyle. We focused on the mechanism by which atopic dermatitis leads to hypohidrosis and confirmed that histamine inhibits acetylcholinergic sweating. Acetylcholine promotes the phosphorylation of glycogen synthesis kinase 3β (GSK3β) in the sweat-gland secretory cells and leads to sensible perspiration. By suppressing the phosphorylation of GSK3β, histamine inhibits the movement of sweat from the sweat-gland secretory cells through the sweat ducts, which could presumably be demonstrated by dynamic observations of the sweat glands using two-photon microscopy. It is expected that the discovery of new factors that control sweat-gland function can contribute to the treatment of diseases associated with dyshidrosis. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Pituitary Tumors

MedlinePlus

... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

Radiotherapy Dose-Volume Effects on Salivary Gland Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deasy, Joseph O., E-mail: jdeasy@radonc.wustl.ed; Moiseenko, Vitali; Marks, Lawrence

2010-03-01

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. Amore » lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.« less

A comparative study of modified transcanalicular diode laser dacryocystorhinostomy versus conventional transcanalicular diode laser dacryocystorhinostomy.

PubMed

Feijó, Eduardo Damous; Caixeta, Juliana Alves; de Souza Nery, Ana Carla; Limongi, Roberto Murillo; Matayoshi, Suzana

2017-08-01

External dacryocystorhinostomy (DCR) is the gold standard surgical technique for the treatment of primary acquired nasolacrimal duct obstruction (PANDO). However, new techniques such as endoscopic DCR and transcanalicular dacryocystorhinostomy (T-DCR) are being studied in an attempt to reduce surgical time, avoid external scarring and preserve the lacrimal pump while achieving the same efficacy. The purpose of this study was to compare the efficacy between conventional T-DCR and modified transcanalicular dacryocystorhinostomy (MT-DCR) in patients with PANDO. MT-DCR is performed to remove nasal mucosa prior to laser osteotomy. This is a comparative, prospective, interventionist and randomized study. Patients with PANDO were selected to undergo MT-DCR or T-DCR by blocked randomization. PANDO was diagnosed based on clinical presentation, dye disappearance test and dacryocystography. All of the procedures were performed by the same surgery team members. Anatomical success outcome was defined as positive lacrimal syringing and functional success outcome was defined as the absence or improvement of epiphora. A total of 44 surgical procedures were performed (22 MT-DCR and 22 T-DCR). In the case of MT-DCR, the anatomical and functional success rates after 12 months were 90 and 86%, respectively. After T-DCR, these rates were 77 and 72%, respectively (p = 0.162). MT-DCR and T-DCR are both safe and fast procedures with low morbidity and well-tolerated.

Post-metamorphic development of skin glands in a true toad: Parotoids versus dorsal skin.

PubMed

Regueira, Eleonora; Dávila, Camila; Sassone, Alina G; O'Donohoe, María E Ailín; Hermida, Gladys N

2017-05-01

Chemical defenses in amphibians are a common antipredatory and antimicrobial strategy related to the presence of dermal glands that synthesize and store toxic or unpalatable substances. Glands are either distributed throughout the skin or aggregated in multiglandular structures, being the parotoids the most ubiquitous macrogland in toads of Bufonidae. Even though dermal glands begin to develop during late-larval stages, many species, including Rhinella arenarum, have immature glands by the end of metamorphosis, and their post-metamorphic growth is unknown. Herein, we compared the post-metamorphic development of parotoids and dorsal glands by histological and allometric studies in a size series of R. arenarum. Histological and histochemical studies to detect proteins, acidic glycoconjugates, and catecholamines, showed that both, parotoids and dorsal glands, acquire characteristics of adults in individuals larger than 50 mm; that is, a moment in which the cryptic coloration disappears. Parotoid height increased allometrically as a function of body size, whereas the size of small dorsal glands decreased with body size. The number of glands in the dorsum was not linearly related to body size, appearing to be an individual characteristic. Only adult specimens had intraepithelial granular glands in the duct of the largest glands of the parotoids. Since toxic secretions accumulate in the central glands of parotoids, allometric growth of parotoids may translate into greater protection from predators in the largest animals. Conversely, large glands in the dorsum, which produce a proteinaceous secretion of unknown function, grow isometrically to body size. Some characteristics, like intraepithelial glands in the ducts and basophilic glands in the dorsum, are limited to adults. © 2017 Wiley Periodicals, Inc.

In Vivo Evidence for Epidermal Growth Factor Receptor (EGFR)-mediated Release of Prolactin from the Pituitary Gland

PubMed Central

Dahlhoff, Maik; Blutke, Andreas; Wanke, Rüdiger; Wolf, Eckhard; Schneider, Marlon R.

2011-01-01

Members of the epidermal growth factor receptor (EGFR/ERBB) system are essential local regulators of mammary gland development and function. Emerging evidence suggests that EGFR signaling may also influence mammary gland activity indirectly by promoting the release of prolactin from the pituitary gland in a MAPK and estrogen receptor-α (ERα)-dependent manner. Here, we report that overexpression of the EGFR ligand betacellulin (BTC) causes a lactating-like phenotype in the mammary gland of virgin female mice including the major hallmarks of lactogenesis. BTC transgenic (BTC-tg) females showed reduced levels of prolactin in the pituitary gland and increased levels of the hormone in the circulation. Furthermore, treatment of BTC-tg females with bromocriptine, an inhibitor of prolactin secretion, blocked the development of the lactation-like phenotype, suggesting that it is caused by central release of prolactin rather than by local actions of BTC in the mammary gland. Introduction of the antimorphic Egfr allele Wa5 also blocked the appearance of the mammary gland alterations, revealing that the phenotype is EGFR-dependent. We detected an increase in MAPK activity, but unchanged phosphorylation of ERα in the pituitary gland of BTC-tg females as compared with control mice. These results provide the first functional evidence in vivo for a role of the EGFR system in regulating mammary gland activity by modulating prolactin release from the pituitary gland. PMID:21914800

HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

EPA Science Inventory

Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

Abstract
The studies review...

Notch-Dependent Pituitary SOX2+ Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland

PubMed Central

Zhu, Xiaoyan; Tollkuhn, Jessica; Taylor, Havilah; Rosenfeld, Michael G.

2015-01-01

Summary Although SOX2+ stem cells are present in the postnatal pituitary gland, how they are regulated molecularly and whether they are required for pituitary functions remain unresolved questions. Using a conditional knockout animal model, here we demonstrate that ablation of the canonical Notch signaling in the embryonic pituitary gland leads to progressive depletion of the SOX2+ stem cells and hypoplastic gland. Furthermore, we show that the SOX2+ stem cells initially play a significant role in contributing to postnatal pituitary gland expansion by self-renewal and differentiating into distinct lineages in the immediate postnatal period. However, we found that within several weeks postpartum, the SOX2+ stem cells switch to an essentially dormant state and are no longer required for homeostasis/tissue adaptation. Our results present a dynamic tissue homeostatic model in which stem cells provide an initial contribution to the growth of the neonatal pituitary gland, whereas the mature gland can be maintained in a stem cell-independent fashion. PMID:26651607

On approaches to the functional restoration of salivary glands damaged by radiation therapy for head and neck cancer, with a review of related aspects of salivary gland morphology and development.

PubMed

Redman, R S

2008-06-01

Radiation therapy for cancer of the head and neck can devastate the salivary glands and partially devitalize the mandible and maxilla. As a result, saliva production is drastically reduced and its quality adversely altered. Without diligent home and professional care, the teeth are subject to rapid destruction by caries, necessitating extractions with attendant high risk of necrosis of the supporting bone. Innovative techniques in delivery of radiation therapy and administration of drugs that selectively protect normal tissues can reduce significantly the radiation effects on salivary glands. Nonetheless, many patients still suffer severe oral dryness. I review here the functional morphology and development of salivary glands as these relate to approaches to preventing and restoring radiation-induced loss of salivary function. The acinar cells are responsible for most of the fluid and organic material in saliva, while the larger ducts influence the inorganic content. A central theme of this review is the extent to which the several types of epithelial cells in salivary glands may be pluripotential and the circumstances that may influence their ability to replace cells that have been lost or functionally inactivated due to the effects of radiation. The evidence suggests that the highly differentiated cells of the acini and large ducts of mature glands can replace themselves except when the respective pools of available cells are greatly diminished via apoptosis or necrosis owing to severely stressful events. Under the latter circumstances, relatively undifferentiated cells in the intercalated ducts proliferate and redifferentiate as may be required to replenish the depleted pools. It is likely that some, if not many, acinar cells may de-differentiate into intercalated duct-like cells and thus add to the pool of progenitor cells in such situations. If the stress is heavy doses of radiation, however, the result is not only the death of acinar cells, but also a marked decline in functional differentiation and proliferative capacity of all of the surviving cells, including those with progenitor capability. Restoration of gland function, therefore, seems to require increasing the secretory capacity of the surviving cells, or replacing the acinar cells and their progenitors either in the existing gland remnants or with artificial glands.

"Sebocytes' makeup": novel mechanisms and concepts in the physiology of the human sebaceous glands.

PubMed

Tóth, Balázs I; Oláh, Attila; Szöllosi, Attila G; Czifra, Gabriella; Bíró, Tamás

2011-06-01

The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a "passive" cutaneous "relic" to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an "active" neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.

A Para-Canalicular Abscess Resembling an Inflamed Chalazion

PubMed Central

Almaliotis, Diamantis; Nakos, Elias; Siempis, Thomas; Koletsa, Triantafyllia; Kostopoulos, Ioannis; Chatzipantazi, Maria; Karampatakis, Vasileios

2013-01-01

Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis). When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed. PMID:23762696

Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PubMed Central

Rosenfield, Sonia M.; Bowden, Emma T.; Cohen-Missner, Shani; Gibby, Krissa A.; Ory, Virginie; Henke, Ralf T.; Riegel, Anna T.; Wellstein, Anton

2012-01-01

Expression of the heparin-binding growth factor, pleiotrophin (PTN) in the mammary gland has been reported but its function during mammary gland development is not known. We examined the expression of PTN and its receptor ALK (Anaplastic Lymphoma Kinase) at various stages of mouse mammary gland development and found that their expression in epithelial cells is regulated in parallel during pregnancy. A 30-fold downregulation of PTN mRNA expression was observed during mid-pregnancy when the mammary gland undergoes lobular-alveolar differentiation. After weaning of pups, PTN expression was restored although baseline expression of PTN was reduced significantly in mammary glands of mice that had undergone multiple pregnancies. We found PTN expressed in epithelial cells of the mammary gland and thus used a monoclonal anti-PTN blocking antibody to elucidate its function in cultured mammary epithelial cells (MECs) as well as during gland development. Real-time impedance monitoring of MECs growth, migration and invasion during anti-PTN blocking antibody treatment showed that MECs motility and invasion but not proliferation depend on the activity of endogenous PTN. Increased number of mammospheres with laminin deposition after anti-PTN blocking antibody treatment of MECs in 3D culture and expression of progenitor markers suggest that the endogenously expressed PTN inhibits the expansion and differentiation of epithelial progenitor cells by disrupting cell-matrix adhesion. In vivo, PTN activity was found to inhibit ductal outgrowth and branching via the inhibition of phospho ERK1/2 signaling in the mammary epithelial cells. We conclude that PTN delays the maturation of the mammary gland by maintaining mammary epithelial cells in a progenitor phenotype and by inhibiting their differentiation during mammary gland development. PMID:23077670

Exaggerated thyroid stimulating hormone secretion in children exposed to the Chernobyl nuclear reactor catastrophe.

PubMed

Boyarskaya, O Y; Kopilova, O V

2008-02-01

We present results of a long-term study of the morpho-functional state of the thyroid gland and of the functional capacities of the hypothalamic-hypophyseal system, as shown by thyrotropin releasing hormone stimulation, in different groups of children who suffered from the Chernobyl accident. It was shown that the thyroid gland of the children who were evacuated from the 30-km zone was damaged most severely due to the influence of radioactive iodine (131I). Living on radionuclide-polluted territories in conditions of iodine deficiency has been an additional contributory factor in the development of thyroid gland diseases. Latent functional deficiency of the hypothalamic-hypophyseal system can be one of the reasons leading to oncopathology of the thyroid gland.

Is visual assessment of thyroid attenuation on unenhanced CT of the chest useful for detecting hypothyroidism?

PubMed

Maldjian, P D; Chen, T

2016-11-01

To determine if visual assessment of the attenuation of morphologically normal appearing thyroid glands on unenhanced computed tomography (CT) of the chest is useful for identifying patients with decreased thyroid function. This was a retrospective study of 765 patients who underwent both unenhanced CT of the chest and thyroid function tests performed within 1 year of the CT examination. Attenuation of the thyroid gland was visually assessed in each patient relative to the attenuation of the surrounding muscles to categorise the gland as "low attenuation" (attenuation similar to surrounding muscles) or "high attenuation" (attenuation greater than surrounding muscles). Thyroid attenuation was quantitatively measured in each case to determine the validity of the visual assessment. Results of thyroid function tests were used to classify thyroid function as hypothyroid, euthyroid, or hyperthyroid. Data were analysed to determine the relationship between visual assessment of thyroid attenuation and status of thyroid function. Thyroid glands of low attenuation were present in 4.2% (32/765) of the patients. Nearly half (47%) of the patients with low-attenuation thyroids had hypofunctioning thyroid glands. Compared to patients with high-attenuation thyroids, patients with low-attenuation thyroids were significantly more likely to have decreased thyroid function (clinical and subclinical hypothyroidism) and significantly less likely to be euthyroid (p<0.0001). Quantitative measurement of thyroid attenuation confirmed the validity of the visual assessment. Low attenuation of an otherwise normal-appearing thyroid gland on unenhanced CT of the chest is strongly associated with decreased thyroid function. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Assessment of tear osmolarity and other dry eye parameters in post-LASIK eyes.

PubMed

Hassan, Ziad; Szalai, Eszter; Berta, Andras; Modis, Laszlo; Nemeth, Gabor

2013-07-01

To assess the tear osmolarity using the TearLab device after laser in situ keratomileusis (LASIK) and to compare the values with those obtained by traditional tear film tests before and after the procedure. Thirty eyes of 15 refractive surgery candidates (5 men and 10 women of mean age: 30.55 ± 11.79 years) were examined. Using a special questionnaire (Ocular Surface Disease Index), subjective dry eye complaints were evaluated, and then, the tear osmolarity was measured with the TearLab system (TearLab Corporation) and conventional dry eye tests were carried out. Examinations were performed preoperatively and at 1, 30, and 60 days after the surgery. The mean value of tear osmolarity was 303.62 ± 12.29 mOsm/L before the surgery and 303.58 ± 20.14 mOsm/L at 60 days after the treatment (P = 0.69). Mean lid parallel conjunctival folds value was 0.68 ± 0.68 before the procedure and 0.58 ± 0.65 subsequent to surgery (P = 0.25). Meibomian gland dysfunction was not detected. No significant deviation was observed in the values of Schirmer test, corneal staining, tear break-up time, and lid parallel conjunctival folds when compared with postoperatively obtained values during the follow-up period (P > 0.05). During LASIK flap creation, intact corneal innervation is damaged, and the ocular surface lacrimal functional unit can be impaired. In our study, no abnormal dry eye test results were observed before or after the procedure. Based on our results, LASIK treatment is safe for dry eye involving the administration of adequate artificial tears for a minimum of 3 months.

Relation of Sensory Peripheral Neuropathy in Sjögren Syndrome to anti-Ro/SSA

PubMed Central

Scofield, Amanda K.; Radfar, Lida; Ice, John; Vista, Evan; Anaya, Juan-Manuel; Houston, Glen; Lewis, David; Stone, Donald U.; Chodosh, James; Hefner, Kimberly; Lessard, Christopher J.; Moser, Kathy L.; Scofield, R. Hal

2013-01-01

Background Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. Methods Eight-eight patients attending a dry eyes-dry mouth clinic were classified as primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B12 levels were determined using an enzyme-linked microtiter plate assay. Results Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (χ2=8.46, p=0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) of these had neuropathy (χ2 =5.587, p=0.018 compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B12 levels to neuropathy among these patients with Sjögren syndrome. Conclusion Sensory peripheral neuropathy is common among patients with Sjögren syndrome, and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion. PMID:22955477

[What is the role of contact lenses within the scope of electronystagmography?].

PubMed

Schmäl, F; Stoll, W

1997-10-01

During electronystagmography it is necessary to correct detective vision for calibration, smooth pursuit, and saccadic eye movements. Therefore more and more people use contact lenses instead of normal glasses. Given the lack of detailed information about this phenomenon, in the current literature we decided to investigate the influence of soft contact lenses on electronystagmography. The aim of this study was to find out differences in the results of electronystagmography between using glasses or contact lenses. Our investigation involved 20 vestibular healthy human subjects with myopia. In the first part of the examination they used their contact lenses and in the second part they were wearing normal glasses. After measuring the calibration potential we wanted to see if contact lenses would increase the rate of artifacts in the electronystagmogram. Then we attempted to determine whether contact lenses would an influence on the registration of the optokinetic nystagmus. Induced saccadic eye movements were recorded and analysed. Contact lenses had a negative influence neither on the calibration potential nor on the rate of artifacts. The latency of the saccadic eye movements also showed no differences between both parts of this investigation. Only the velocity of the saccades and the gain value during the optokinetic test were reduced when glasses were used. Contact lenses may stimulate the secretory function of the lacrimal gland and thus decrease friction forces. It is also possible that the reduced image size produced or the reduction-effect of minus by glasses in near sighted persons negatively influences eyeball velocity. In summary, our study demonstrates that contact lenses do not have a negative influence on electronystagmography. Therefore electronystagmographic studies of patients with contact lenses are permissible for purposes of documenting a medical opinion.

[Evaluation of salivary gland function in women with autoimmune thyroid diseases].

PubMed

Koczor-Rozmus, Aleksandra; Zwirska-Korczala, Krystyna; Sadlak-Nowicka, Jadwiga; Ilewicz, Leşzek; Mayer-Parka, Danuta; Wierucka-Młynarczyk, Beata

2003-01-01

The function of the salivary glands is regulated by nervous system which influences salivary circulation. Moreover the volume of secreted saliva depends on the humoral agents, including thyroid hormones. The aim of the study was to determine the quantity of the secreted mixed resting and stimulated saliva in women with autoimmune thyroid diseases (AITD) depending on the function of the thyroid gland (hyperthyroidism, hypothyroidism and euthyroidism). The association between thyroid antibody concentrations (TPO-Ab, Tg-Ab, TR-Ab) and volume of secreted saliva was also examined. Studies were performed in 106 women suffering from AITD and 15 healthy volunteers. In hyperthyroid women there was a decrease in volumes of resting (57.14%) and stimulated (89.29%) saliva. Similarly, a decrease in secretion of resting (75%) and stimulated (66.67%) saliva was shown in hypothyroid women. In euthyroid patients with AITD there was a partial normalisation of salivary glands function. The negative correlation between concentrations of TPO-Ab, Tg-Ab and the volume of resting and stimulated saliva was found. In conclusion, AITD may be associated with disturbances in salivary secretion which depends on thyroid hormones production. It can be suggested that autoimmunological processes within salivary glands may influence their function.

[Meibomian gland disfunction in computer vision syndrome].

PubMed

Pimenidi, M K; Polunin, G S; Safonova, T N

2010-01-01

This article reviews ethiology and pathogenesis of dry eye syndrome due to meibomian gland disfunction (MDG). It is showed that blink rate influences meibomian gland functioning and computer vision syndrome development. Current diagnosis and treatment options of MDG are presented.

Scintigraphic assessment of salivary function after intensity-modulated radiotherapy for head and neck cancer: correlations with parotid dose and quality of life.

PubMed

Chen, Wen-Cheng; Lai, Chia-Hsuan; Lee, Tsair-Fwu; Hung, Chao-Hsiung; Liu, Kuo-Chi; Tsai, Ming-Fong; Wang, Wen-Hung; Chen, Hungcheng; Fang, Fu-Ming; Chen, Miao-Fen

2013-01-01

We investigated salivary function using quantitative scintigraphy and sought to identify functional correlations between parotid dose and quality of life (QoL) for head and neck cancer (HNC) patients receiving intensity-modulated radiotherapy (IMRT). Between August, 2007 and June, 2008, 31 patients treated IMRT for HNC were enrolled in this prospective study. Salivary excretion function (SEF) was previously measured by salivary scintigraphy at annual intervals for 2 years after IMRT. A dose-volume histogram of each parotid gland was calculated, and the normal tissue complication probability (NTCP) was used to determine the tolerance dose. QoL was longitudinally assessed by the EORTC QLQ-C30 and H&N35 questionnaires prior to RT, and at one, three, 12 and 24 months after RT. A significant correlation was found between the reduction of SEF and the mean parotid dose measured at 1 year (correlation coefficient, R(2)=0.651) and 2 years (R(2)=0.310) after IMRT (p<0.001). The TD(50) of the parotid gland at 1 year after IMRT is 43.6 Gy, comparable to results from western countries. We further found that contralateral parotid and submandibular gland function preservation was correlated with reduced sticky saliva and a better QoL compared to the functional preservation of both parotid glands, as determined by the EORTC QLQ-H&N35 questionnaire. A significant correlation was found between the reduction of SEF and the mean parotid dose. Preservation of contralateral parotid and submandibular gland function predicts a better QoL compared to preservation of the function of both parotid glands. Copyright © 2012 Elsevier Ltd. All rights reserved.

Epigenetic Modifications Unlock the Milk Protein Gene Loci during Mouse Mammary Gland Development and Differentiation

PubMed Central

Rijnkels, Monique; Freeman-Zadrowski, Courtneay; Hernandez, Joseph; Potluri, Vani; Wang, Liguo; Li, Wei; Lemay, Danielle G.

2013-01-01

Background Unlike other tissues, development and differentiation of the mammary gland occur mostly after birth. The roles of systemic hormones and local growth factors important for this development and functional differentiation are well-studied. In other tissues, it has been shown that chromatin organization plays a key role in transcriptional regulation and underlies epigenetic regulation during development and differentiation. However, the role of chromatin organization in mammary gland development and differentiation is less well-defined. Here, we have studied the changes in chromatin organization at the milk protein gene loci (casein, whey acidic protein, and others) in the mouse mammary gland before and after functional differentiation. Methodology/Principal Findings Distal regulatory elements within the casein gene cluster and whey acidic protein gene region have an open chromatin organization after pubertal development, while proximal promoters only gain open-chromatin marks during pregnancy in conjunction with the major induction of their expression. In contrast, other milk protein genes, such as alpha-lactalbumin, already have an open chromatin organization in the mature virgin gland. Changes in chromatin organization in the casein gene cluster region that are present after puberty persisted after lactation has ceased, while the changes which occurred during pregnancy at the gene promoters were not maintained. In general, mammary gland expressed genes and their regulatory elements exhibit developmental stage- and tissue-specific chromatin organization. Conclusions/Significance A progressive gain of epigenetic marks indicative of open/active chromatin on genes marking functional differentiation accompanies the development of the mammary gland. These results support a model in which a chromatin organization is established during pubertal development that is then poised to respond to the systemic hormonal signals of pregnancy and lactation to achieve the full functional capacity of the mammary gland. PMID:23301053

Dry eye disease: pathophysiology, classification, and diagnosis.

PubMed

Perry, Henry D

2008-04-01

Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface that results in eye discomfort, visual disturbance, and often ocular surface damage. Although recent research has made progress in elucidating DED pathophysiology, currently there are no uniform diagnostic criteria. This article discusses the normal anatomy and physiology of the lacrimal functional unit and the tear film; the pathophysiology of DED; DED etiology, classification, and risk factors; and DED diagnosis, including symptom assessment and the roles of selected diagnostic tests.

Frequency of simultaneous nasal procedures in endoscopic dacryocystorhinostomy.

PubMed

Figueira, Edwin; Al Abbadi, Zaid; Malhotra, Raman; Wilcsek, Geoffrey; Selva, Dinesh

2014-01-01

To assess the frequency of simultaneous nasal procedures in powered endoscopic dacryocystorhinostomy performed by oculoplastic surgeons. Retrospective, multicenter study. Demographic, clinical, and surgical data of consecutive endoscopic dacryocystorhinostomy cases at 3 oculoplastic centers, over periods of 6, 4, and 2.2 years, respectively, were reviewed. The rates of simultaneous nasal procedures (septoplasty, turbinectomy, and polypectomy) were studied. Complication rates in the patients who had simultaneous endonasal procedures were analyzed. Five hundred seventy-six cases (mean age: 63.2 years [16.2-94 years], women: 67.3%). Of the total cohort of patients, 14.1% required a simultaneous endonasal procedure during endoscopic dacryocystorhinostomy, 11.9% (range among surgeons: 5.2%-15%) required septoplasty, 1.5% required middle turbinate surgery, and 0.34% required polypectomy. Of the 81 patients with concomitant procedures, 1 had postoperative epistaxis, and 1 had an asymptomatic septal adhesion. The anatomical and functional success rates for the entire cohort were 95.6% and 87.8%, respectively. A significant proportion of patients undergoing endoscopic dacryocystorhinostomy may require concomitant endonasal procedures. Hence, endonasal lacrimal surgeons using techniques that aim to marsupialize the entire lacrimal sac may benefit from expertize in the management of concomitant nasal pathologic study.

Persistence of hAQP1 expression in human salivary gland cells following AdhAQP1 transduction is associated with a lack of methylation of hCMV promoter

PubMed Central

Zheng, C; Baum, BJ; Liu, X; Goldsmith, CM; Perez, P; Jang, S-I; Cotrim, AP; McCullagh, L; Ambudkar, IS; Alevizos, I

2017-01-01

In 2012, we reported that 5 out of 11 subjects in a clinical trial (NCT00372320) administering AdhAQP1 to radiation-damaged parotid glands showed increased saliva flow rates and decreased symptoms over the initial 42 days. AdhAQP1 is a first-generation, E1-deleted, replication-defective, serotype 5 adenoviral vector encoding human aquaporin-1 (hAQP1). This vector uses the human cytomegalovirus enhancer/promoter (hCMVp). As subject peak responses were at times much longer (7–42 days) than expected, we hypothesized that the hCMVp may not be methylated in human salivary gland cells to the extent previously observed in rodent salivary gland cells. This hypothesis was supported in human salivary gland primary cultures and human salivary gland cell lines after transduction with AdhAQP1. Importantly, hAQP1 maintained its function in those cells. Conversely, when we transduced mouse and rat cell lines in vitro and submandibular glands in vivo with AdhAQP1, the hCMVp was gradually methylated over time and associated with decreased hAQP1 expression and function in vitro and decreased hAQP1 expression in vivo. These data suggest that the hCMVp in AdhAQP1was probably not methylated in transduced human salivary gland cells of responding subjects, resulting in an unexpectedly longer functional expression of hAQP1. PMID:26177970

Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function.

PubMed

Concepcion, Axel R; Vaeth, Martin; Wagner, Larry E; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S; Cuk, Mario; Yule, David I; Feske, Stefan

2016-11-01

Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice.

[The thyroid gland in emotional and pain stress].

PubMed

Akhmetov, I Z

1987-01-01

The reaction of wild rodent thyroid gland on emotional and painful stress appearing as a result of animal's catching has been studied. The thyroid activity has been shown to raise considerably during the primary stage of stress reaction. Later on the function of the gland normalizes in animals without trauma and in traumatized animals it becomes weaker. The complete normalization of the thyroid function in traumatized animals coincides with osteal regeneration according to time.

Meibocyte differentiation and renewal: Insights into novel mechanisms of meibomian gland dysfunction (MGD).

PubMed

Hwang, Ho Sik; Parfitt, Geraint J; Brown, Donald J; Jester, James V

2017-10-01

This paper reviews our current understanding of age-related meibomian gland dysfunction (MGD) and the role of the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ), in the regulation of meibomian gland function, meibocyte differentiation and lipid synthesis. The studies suggest that PPARγ is a master regulator of meibocyte differentiation and function, whose expression and nuclear signaling coupled with meibocyte renewal is altered during aging, potentially leading to atrophy of the meibomian gland as seen in clinical MGD. Study of meibomian gland stem cells also suggest that there is a limited number of precursor meibocytes that provide progeny to the acini, that may be susceptible to exhaustion as occurs during aging and other environmental factors. Further study of pathways regulating PPARγ expression and function as well as meibocyte stem cell maintenance may provide clues to establishing cellular and molecular mechanisms underlying MGD and the development of novel therapeutic strategies to treating this disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biomacromolecule conjugated nanofiber scaffold for salivary gland tissue engineering

NASA Astrophysics Data System (ADS)

Jayarathanam, Kavitha

Xerostomia or dry mouth, resulting from loss of salivary gland secretion can be alleviated by tissue engineering approaches to restore glandular cell function. Engineering an artificial salivary gland structure requires closely mimicking the natural environment, both physically and functionally, to promote epithelial cell proliferation, monolayer formation and apico-basal polarization. While the physical structure of the salivary gland extracellular matrix (ECM) can be reconstructed using biocompatible nanofiber scaffolds, the chemical signals from ECM macromolecules are equally involved in the gland morphogenesis. In these glands, Hyaluronic acid (HA), a biomacromolecule that is a major component of the ECM, plays a crucial role in recruiting growth factors to improve cell viability and growth in these glands. Another molecule of interest that improved salivary epithelial cell viability and apico-basal differentiation is laminin, a major protein found in the basement membrane. We hypothesize that these biomacromolecules, when conjugated nanofiber scaffolds, will provide the essential chemical signals that promote cell viability, proliferation, polarity in the salivary cell line of interest. These morphological changes will in turn promote the secretory function (salivary production). The nanofiber scaffold consisting of poly(lactic-co-glycolic)acid is conjugated with HA using a polyethylene glycol (PEG) diamine crosslinker. This conjugation was confirmed using fluorescence spectrometry, water contact angle test and immunocytochemistry analysis using confocal microscopy. The effect of HA in promoting cell survival in-vitro was established with MTT assay using SIMS (mouse submandibular immortalized ductal SIMS cells) cells. The effect of HA in improving the apico - basal polarity of SIMS cells will be assessed. Chemical modification of synthetic nanopolymeric scaffolds with ECM molecules e.g., HA, laminin are the next step towards developing "smart scaffolds", that can be used to specifically induce proper salivary gland function. These scaffolds can potentially be used to provide a viable approach for creating future artificial tissue engineered glands.

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.

PubMed

Tan, J; Buache, E; Alpy, F; Daguenet, E; Tomasetto, C-L; Ren, G-S; Rio, M-C

2014-07-31

MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11-/-) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11-/- epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

Analysis of proteome dynamics inside the silk gland lumen of Bombyx mori.

PubMed

Dong, Zhaoming; Zhao, Ping; Zhang, Yan; Song, Qianru; Zhang, Xiaolu; Guo, Pengchao; Wang, Dandan; Xia, Qingyou

2016-04-22

The silk gland is the only organ where silk proteins are synthesized and secreted in the silkworm, Bombyx mori. Silk proteins are stored in the lumen of the silk gland for around eight days during the fifth instar. Determining their dynamic changes is helpful for clarifying the secretion mechanism of silk proteins. Here, we identified the proteome in the silk gland lumen using liquid chromatography-tandem mass spectrometry, and demonstrated its changes during two key stages. From day 5 of the fifth instar to day 1 of wandering, the abundances of fibroins, sericins, seroins, and proteins of unknown functions increased significantly in different compartments of the silk gland lumen. As a result, these accumulated proteins constituted the major cocoon components. In contrast, the abundances of enzymes and extracellular matrix proteins decreased in the silk gland lumen, suggesting that they were not the structural constituents of silk. Twenty-five enzymes may be involved in the regulation of hormone metabolism for proper silk gland function. In addition, the metabolism of other non-proteinous components such as chitin and pigment were also discussed in this study.

Analysis of proteome dynamics inside the silk gland lumen of Bombyx mori

PubMed Central

Dong, Zhaoming; Zhao, Ping; Zhang, Yan; Song, Qianru; Zhang, Xiaolu; Guo, Pengchao; Wang, Dandan; Xia, Qingyou

2016-01-01

The silk gland is the only organ where silk proteins are synthesized and secreted in the silkworm, Bombyx mori. Silk proteins are stored in the lumen of the silk gland for around eight days during the fifth instar. Determining their dynamic changes is helpful for clarifying the secretion mechanism of silk proteins. Here, we identified the proteome in the silk gland lumen using liquid chromatography–tandem mass spectrometry, and demonstrated its changes during two key stages. From day 5 of the fifth instar to day 1 of wandering, the abundances of fibroins, sericins, seroins, and proteins of unknown functions increased significantly in different compartments of the silk gland lumen. As a result, these accumulated proteins constituted the major cocoon components. In contrast, the abundances of enzymes and extracellular matrix proteins decreased in the silk gland lumen, suggesting that they were not the structural constituents of silk. Twenty-five enzymes may be involved in the regulation of hormone metabolism for proper silk gland function. In addition, the metabolism of other non-proteinous components such as chitin and pigment were also discussed in this study. PMID:27102218

Database of cattle candidate genes and genetic markers for milk production and mastitis

PubMed Central

Ogorevc, J; Kunej, T; Razpet, A; Dovc, P

2009-01-01

A cattle database of candidate genes and genetic markers for milk production and mastitis has been developed to provide an integrated research tool incorporating different types of information supporting a genomic approach to study lactation, udder development and health. The database contains 943 genes and genetic markers involved in mammary gland development and function, representing candidates for further functional studies. The candidate loci were drawn on a genetic map to reveal positional overlaps. For identification of candidate loci, data from seven different research approaches were exploited: (i) gene knockouts or transgenes in mice that result in specific phenotypes associated with mammary gland (143 loci); (ii) cattle QTL for milk production (344) and mastitis related traits (71); (iii) loci with sequence variations that show specific allele-phenotype interactions associated with milk production (24) or mastitis (10) in cattle; (iv) genes with expression profiles associated with milk production (207) or mastitis (107) in cattle or mouse; (v) cattle milk protein genes that exist in different genetic variants (9); (vi) miRNAs expressed in bovine mammary gland (32) and (vii) epigenetically regulated cattle genes associated with mammary gland function (1). Fourty-four genes found by multiple independent analyses were suggested as the most promising candidates and were further in silico analysed for expression levels in lactating mammary gland, genetic variability and top biological functions in functional networks. A miRNA target search for mammary gland expressed miRNAs identified 359 putative binding sites in 3′UTRs of candidate genes. PMID:19508288

Gross morphology and ultrastructure of salivary glands of the mute cicada Karenia caelatata Distant (Hemiptera: Cicadoidea).

PubMed

Zhong, Hai-ying; Wei, Cong; Zhang, Ya-lin

2013-02-01

Salivary glands of the cicada Karenia caelatata Distant were investigated using light microscopy and transmission electron microscopy. The salivary glands are paired structures and consist of principal glands and accessory glands. The principal gland is subdivided into anterior lobe and posterior lobe; the former contains about 34-39 long digitate lobules, while the latter contains approximately 30-33 long digitate lobules and 13-22 short digitate lobules. These short digitate lobules, about one fifth or sixth as long as the long digitate lobules, locate at the base of the long digitate lobules of posterior lobe. All of these digitate lobules vary in size, disposition, length and shape. The anterior lobe and the posterior lobe are connected by an anterior-posterior duct. Two efferent salivary ducts, which connect with the posterior lobe, fuse to form a common duct. The accessory gland is composed of three parts: a greatly tortuous and folded accessory salivary tube, a circlet of gular gland constituting of several acini of the same size, and a non-collapsible accessory salivary duct. The digitate lobules and gular glands possess secretory cells containing abundant secretory granules vary in size, shape, and electron density, as might indicate different materials are synthesized in different secretory regions. The anterior-posterior duct lines with a player of cuticular lining, and cells beneath the cuticular lining lack of basal infoldings, as suggests the duct serves just to transport secretions. The accessory salivary duct is lined with cuticular lining; cells of the duct have well developed basal infoldings associated with abundant mitochondria, as probably suggests the duct is a reabsorptive region of ions. The cells of the accessory salivary tube possess deep basal infoldings and well developed apical dense microvilli, indicating the cells of the tube are secretory in function. Concentric lamellar structures and a peculiar structure with abundant membrane-bound vesicles and secretory granules are observed for the first time, but their derivation and function remain unclear. The morphology and ultrastructure differences observed in the principal glands and accessory gland of the salivary glands of K. caelatata indicate that the sheath saliva was secreted by the principal glands, and the watery saliva was secreted by the accessory salivary glands. Rod-shaped microorganisms are found in the salivary glands (i.e., accessory salivary duct, gular gland, and long digitate lobule of salivary glands) for the first time, and their identity, function, and relationship to microorganisms residing in the salivary glands and/or other parts of alimentary canal of other cicadas need to be investigated further. Copyright © 2012 Elsevier Ltd. All rights reserved.

Characterization of human pineal gland proteome.

PubMed

Yelamanchi, Soujanya D; Kumar, Manish; Madugundu, Anil K; Gopalakrishnan, Lathika; Dey, Gourav; Chavan, Sandip; Sathe, Gajanan; Mathur, Premendu P; Gowda, Harsha; Mahadevan, Anita; Shankar, Susarla K; Prasad, T S Keshava

2016-11-15

The pineal gland is a neuroendocrine gland located at the center of the brain. It is known to regulate various physiological functions in the body through secretion of the neurohormone melatonin. Comprehensive characterization of the human pineal gland proteome has not been undertaken to date. We employed a high-resolution mass spectrometry-based approach to characterize the proteome of the human pineal gland. A total of 5874 proteins were identified from the human pineal gland in this study. Of these, 5820 proteins were identified from the human pineal gland for the first time. Interestingly, 1136 proteins from the human pineal gland were found to contain a signal peptide domain, which indicates the secretory nature of these proteins. An unbiased global proteomic profile of this biomedically important organ should benefit molecular research to unravel the role of the pineal gland in neuropsychiatric and neurodegenerative diseases.

Non-invasive evaluation of the effects of opening & closing of eyes, and of exposure to a minute light beam, as well as to electrical or magnetic field on the melatonin, serotonin, & other neuro-transmitters of human pineal gland representation areas & the heart.

PubMed

Omura, Y; Losco, B M; Takeshige, C

1993-01-01

Using the Bi-Digital O-Ring Test electromagnetic resonance phenomena between 2 identical substances, first the pineal gland representational (rep.) areas were localized on the 5 different locations on the surface of the head using microscope slides of the pineal gland or Melatonin (while the eyes are closed) as a reference control substance. The 3 pineal rep. areas along the mid-line of the head always showed two lobes connected as a "Dumbbell" shape, with one round or oval area at each side of the mid-line. From each side of the head, anterior and superior to the ear, it appeared in a shape resembling the side view of a pineal gland. When both eyes were open, Melatonin, Norepinephrine (NE), and Acetylcholine (ACh) markedly decreased, while Serotonin, Dopamine, and GABA increased significantly in the outer part of the pineal gland rep. areas. When both eyes were closed, Melatonin, NE and ACh increased markedly, with marked decrease in Serotonin, Dopamine and GABA in the outer part of the pineal gland rep. areas. However, in the inner core of the pineal gland rep. area, an opposite response was found. Thus, the pineal gland has 2 main lobes, and functionally each lobe seems to have two concentric areas with an inverse relationship, i.e., a "Functional Cortex" area and a "Functional Core" area. The biochemical changes between the cortex and the core are in an inverse relationship. Melatonin was also found in the S-A node & right side of normal heart when the eyes were closed. When the eyes were open, Melatonin was found in the left side of the heart, as well as the salivary glands, stomach, colon, etc. While both eyes were closed, when a weak light beam was exposed at different parts of the body, such as any part of the upper and lower extremities, Melatonin, NE, and ACh decreased, with an increase in Serotonin, GABA and Dopamine only in the functional cortices of the pineal gland lobes on the same side of the body. Even when both eyes were open, if a very weak narrow beam of light was exposed on any part of the body, Melatonin, NE and ACh decreased, while Serotonin, Dopamine and GABA increased compared with pre-exposure level in only the functional cortices of the pineal gland lobes in the same side of the light exposure, and the opposite effect was also observed in the functional core of the light exposed side only.(ABSTRACT TRUNCATED AT 400 WORDS)

Pheromones and exocrine glands in Isoptera.

PubMed

Costa-Leonardo, Ana Maria; Haifig, Ives

2010-01-01

Termites are eusocial insects that have a peculiar and intriguing system of communication using pheromones. The termite pheromones are composed of a blend of chemical substances and they coordinate different social interactions or activities, including foraging, building, mating, defense, and nestmate recognition. Some of these sociochemicals are volatile, spreading in the air, and others are contact pheromones, which are transmitted by trophallaxis and grooming. Among the termite semiochemicals, the most known are alarm, trail, sex pheromones, and hydrocarbons responsible for the recognition of nestmates. The sources of the pheromones are exocrine glands located all over the termite body. The principal exocrine structures considered pheromone-producing glands in Isoptera are the frontal, mandibular, salivary or labial, sternal, and tergal glands. The frontal gland is the source of alarm pheromone and defensive chemicals, but the mandibular secretions have been little studied and their function is not well established in Isoptera. The secretion of salivary glands involves numerous chemical compounds, some of them without pheromonal function. The worker saliva contains a phagostimulating pheromone and probably a building pheromone, while the salivary reservoir of some soldiers contains defensive chemicals. The sternal gland is the only source of trail-following pheromone, whereas sex pheromones are secreted by two glandular sources, the sternal and tergal glands. To date, the termite semiochemicals have indicated that few molecules are involved in their chemical communication, that is, the same compound may be secreted by different glands, different castes and species, and for different functions, depending on the concentration. In addition to the pheromonal parsimony, recent studies also indicate the occurrence of a synergic effect among the compounds involved in the chemical communication of Isoptera. Copyright © 2010 Elsevier Inc. All rights reserved.

Rationale for anti-inflammatory therapy in dry eye syndrome.

PubMed

de Paiva, C S; Pflugfelder, S C

2008-01-01

Dry eye is a multifactorial condition that results in a dysfunctional lacrimal functional unit. Evidence suggests that inflammation is involved in the pathogenesis of the disease. Changes in tear composition including increased cytokines, chemokines, metalloproteinases and the number of T cells in the conjunctiva are found in dry eye patients and in animal models. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. There are several anti-inflammatory therapies for dry eye that target one or more of the inflammatory mediators/pathways that have been identified and are discussed in detail.

Establishment of Functional Acinar-like Cultures from Human Salivary Glands

PubMed Central

Jang, S.I.; Ong, H.L.; Gallo, A.; Liu, X.; Illei, G.

2015-01-01

Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers—namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients. PMID:25416669

Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation.

PubMed

Marmary, Yitzhak; Adar, Revital; Gaska, Svetlana; Wygoda, Annette; Maly, Alexander; Cohen, Jonathan; Eliashar, Ron; Mizrachi, Lina; Orfaig-Geva, Carmit; Baum, Bruce J; Rose-John, Stefan; Galun, Eithan; Axelrod, Jonathan H

2016-03-01

Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy. ©2016 American Association for Cancer Research.

Repressor of Estrogen Receptor Activity (REA) Is Essential for Mammary Gland Morphogenesis and Functional Activities: Studies in Conditional Knockout Mice

PubMed Central

Park, Sunghee; Zhao, Yuechao; Yoon, Sangyeon; Xu, Jianming; Liao, Lan; Lydon, John; DeMayo, Franco; O'Malley, Bert W.

2011-01-01

Estrogen receptor (ER) is a key regulator of mammary gland development and is also implicated in breast tumorigenesis. Because ER-mediated activities depend critically on coregulator partner proteins, we have investigated the consequences of reduction or loss of function of the coregulator repressor of ER activity (REA) by conditionally deleting one allele or both alleles of the REA gene at different stages of mammary gland development. Notably, we find that heterozygosity and nullizygosity for REA result in very different mammary phenotypes and that REA has essential roles in the distinct morphogenesis and functions of the mammary gland at different stages of development, pregnancy, and lactation. During puberty, mice homozygous null for REA in the mammary gland (REAf/f PRcre/+) showed severely impaired mammary ductal elongation and morphogenesis, whereas mice heterozygous for REA (REAf/+ PRcre/+) displayed accelerated mammary ductal elongation, increased numbers of terminal end buds, and up-regulation of amphiregulin, the major paracrine mediator of estrogen-induced ductal morphogenesis. During pregnancy and lactation, mice with homozygous REA gene deletion in mammary epithelium (REAf/f whey acidic protein-Cre) showed a loss of lobuloalveolar structures and increased apoptosis of mammary alveolar epithelium, leading to impaired milk production and significant reduction in growth of their offspring, whereas body weights of the offspring nursed by females heterozygous for REA were slightly greater than those of control mice. Our findings reveal that REA is essential for mammary gland development and has a gene dosage-dependent role in the regulation of stage-specific physiological functions of the mammary gland. PMID:21862609

Impaired mitochondria and intracellular calcium transients in the salivary glands of obese rats.

PubMed

Ittichaicharoen, Jitjiroj; Apaijai, Nattayaporn; Tanajak, Pongpan; Sa-Nguanmoo, Piangkwan; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-04-01

Long-term consumption of a high-fat diet (HFD) causes not only obese-insulin resistance, but is also associated with mitochondrial dysfunction in several organs. However, the effect of obese-insulin resistance on salivary glands has not been investigated. We hypothesized that obese-insulin resistance induced by HFD impaired salivary gland function by reducing salivation, increasing inflammation, and fibrosis, as well as impairing mitochondrial function and calcium transient signaling. Male Wistar rats (200-220 g) were fed either a ND or an HFD (n = 8/group) for 16 weeks. At the end of week 16, salivary flow rates, metabolic parameters, and plasma oxidative stress were determined. Rats were then sacrificed and submandibular glands were removed to determine inflammation, fibrosis, apoptosis, mitochondrial function and dynamics, and intracellular calcium transient signaling. Long-term consumption of an HFD caused obese-insulin resistance and increased oxidative stress, fibrosis, inflammation, and apoptosis in the salivary glands. In addition, impaired mitochondrial function, as indicated by increased mitochondrial reactive oxygen species, mitochondrial membrane depolarization, and mitochondrial swelling in salivary glands and impaired intracellular calcium regulation, as indicated by a reduced intracellular calcium transient rising rate, decay rates, and amplitude of salivary acinar cells, were observed in HFD-fed rats. However, salivary flow rate and level of aquaporin 5 protein were not different between both groups. Although HFD consumption did not affect salivation, it caused obese-insulin resistance, leading to pathophysiological alteration of salivary glands, including impaired intracellular calcium transients, increased oxidative stress and inflammation, and salivary mitochondrial dysfunction.

The spectrum of STAT functions in mammary gland development

PubMed Central

Hughes, Katherine; Watson, Christine J.

2012-01-01

The signal transducer and activator of transcription (STAT) family of transcription factors have a spectrum of functions in mammary gland development. In some cases these roles parallel those of STATs in other organ systems, while in other instances the function of individual STATs in the mammary gland is specific to this tissue. In the immune system, STAT6 is associated with differentiation of T helper cells, while in the mammary gland, it has a fundamental role in the commitment of luminal epithelial cells to the alveolar lineage. STAT5A is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. By contrast, the initiation of regression following weaning heralds a dramatic and specific activation of STAT3, reflecting its pivotal role in the regulation of cell death and tissue remodeling during mammary involution. Although it has been demonstrated that STAT1 is regulated during a mammary developmental cycle, it is not yet determined whether it has a specific, non-redundant function. Thus, the mammary gland constitutes an unusual example of an adult organ in which different STATs are sequentially activated to orchestrate the processes of functional differentiation, cell death and tissue remodeling. PMID:24058764

Nonmuscarinic neurotoxicity of oxotremorine.

PubMed

Witkin, J M; Alvarado-Garcia, R; Lee, M A; Witkin, K M

1987-04-01

The ability of various treatments to prevent peripheral parasympathetic actions, central effects and lethality of the muscarinic agonist oxotremorine was studied in rats. The percentage of animals exhibiting effects of oxotremorine was dose and time dependent. The ED50 for producing lacrimation, salivation, tremor, convulsions and death was 2.5, 1.3, 1.6, 3.2 and 8.3 mg/kg i.p., respectively. Pretreatment with 5 mg/kg of atropine completely prevented all observable effects of oxotremorine at doses of 5 mg/kg and below. Doses of oxotremorine in excess of 5 mg/kg produced tremor, generalized clonic convulsions and death that could not be prevented by atropine when given at up to 160 mg/kg; lacrimation and salivation were not present in atropine-treated rats. In the presence of 40 mg/kg of atropine, ED50 values for oxotremorine were shifted more than 12-fold for lacrimation, salivation and tremor, whereas convulsions and death were maximally altered by a factor of 2. Scopolamine, benactyzine and benztropine were also incapable of completely preventing tremor, convulsions and death induced by 10 or 15 mg/kg of oxotremorine. Atropine methyl nitrate had effects comparable to atropine sulfate on lacrimation, salivation and lethality induced by oxotremorine (10 or 15 mg/kg) but had no effect on tremor or convulsions. A similar profile of atropine-insensitive effects was produced by pilocarpine and arecoline. Doses of diazepam 4 times higher (4 mg/kg) than necessary to prevent tonic-clonic convulsions induced by pentylenetetrazol were ineffective against tremor, convulsions or death produced by oxotremorine (10 or 15 mg/kg) unless given in conjunction with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

A journey through the pituitary gland: Development, structure and function, with emphasis on embryo-foetal and later development.

PubMed

Musumeci, Giuseppe; Castorina, Sergio; Castrogiovanni, Paola; Loreto, Carla; Leonardi, Rosi; Aiello, Flavia Concetta; Magro, Gaetano; Imbesi, Rosa

2015-01-01

The pituitary gland and the hypothalamus are morphologically and functionally associated in the endocrine and neuroendocrine control of other endocrine glands. They therefore play a key role in a number of regulatory feedback processes that co-ordinate the whole endocrine system. Here we review the neuroendocrine system, from the discoveries that led to its identification to some recently clarified embryological, functional, and morphological aspects. In particular we review the pituitary gland and the main notions related to its development, organization, cell differentiation, and vascularization. Given the crucial importance of the factors controlling neuroendocrine system development to understand parvocellular neuron function and the aetiology of the congenital disorders related to hypothalamic-pituitary axis dysfunction, we also provide an overview of the molecular and genetic studies that have advanced our knowledge in the field. Through the action of the hypothalamus, the pituitary gland is involved in the control of a broad range of key aspects of our lives: the review focuses on the hypothalamic-pituitary-gonadal axis, particularly GnRH, whose abnormal secretion is associated with clinical conditions involving delayed or absent puberty and reproductive dysfunction. Copyright © 2015 Elsevier GmbH. All rights reserved.

[NUCLEAR STRUCTURE IN THE SECRETORY CELLS OF MAMMARY GLANDS IN LACTATING AND NON-LACTATING RATS].

PubMed

Tyutina, K V; Skopichev, V G; Bogolyubov, D S; Bogolyubova, I O

2016-01-01

The features of structural and functional organization of the main nuclear compartments and distribution of their key molecular components (chromatin-remodeling protein ATRX, RNA polymerase I and II, and the splicing factor SC35) has been studied in the nuclei of mammary gland cells at different functional states. No significant differences between the nuclei of the cells in the lactating and non-lactating mammary glands have been revealed at the ultrastructural level. At the same time, photometric analysis has revealed higher intensity of nucleoplasmic immunofluorescent staining of mammary glands in the lactating animals when antibodies against the proteins ATRX and SC35 were used. Apparently, this observation reflects the changes of the structural and functional status of chromatin as well as the redistribution of splicing factors between the sites of their deposition and transcription.

In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine.

PubMed

Howell, G; West, L; Jenkins, C; Lineberry, B; Yokum, D; Rockhold, R

2005-08-18

Muscarinic receptor mediated adverse effects, such as sedation and xerostomia, significantly hinder the therapeutic usefulness of first generation antihistamines. Therefore, second and third generation antihistamines which effectively antagonize the H1 receptor without significant affinity for muscarinic receptors have been developed. However, both in vitro and in vivo experimentation indicates that the third generation antihistamine, desloratadine, antagonizes muscarinic receptors. To fully examine the in vivo antimuscarinic efficacy of desloratadine, two murine and two rat models were utilized. The murine models sought to determine the efficacy of desloratadine to antagonize muscarinic agonist induced salivation, lacrimation, and tremor. Desloratadine's effect on the cardiovascular system was explored in both rodent models. In the pithed rat, both desloratadine (1.0 mg/kg, i.v.) and the muscarinic M2 selective antagonist, methoctramine (0.5 mg/kg, i.v.), inhibited negative inotropic (left ventricular dP/dt) effects caused by oxotremorine, a nonselective muscarinic agonist (p < 0.05). Negative chronotropic effects caused by oxotremorine were inhibited by desloratadine, methoctramine, and the muscarinic M3 selective antagonist, 4-DAMP (1.0 mg/kg, i.v.). A late positive inotropic event observed after the initial decrease was inhibited by all three test compounds with desloratadine and 4-DAMP being the most efficacious. In the conscious animal, inhibition of baroreflex-mediated bradycardia was evaluated. Unlike atropine (0.5 mg/kg, i.v.), desloratadine did not alter this bradycardia. The antimuscarinic action of desloratadine on salivation, lacrimation, and tremor was also explored. In urethane-anesthetized (1.5 g/kg, i.p.) male ICR mice (25-35 g) desloratadine (1.0, 5.0 mg/kg) did not inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, unlike atropine (0.5 mg/kg) and 4-DAMP (1.0 mg/kg). In conscious mice, desloratadine failed to inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, lacrimation, and tremor. However, desloratadine did inhibit oxotremorine-induced tremor in phenylephrine pretreated animals. The presented data demonstrate that the third generation antihistamine, desloratadine, does not significantly antagonize peripheral muscarinic receptors mediating salivation and lacrimation, therefore, xerostomia and dry eyes should not be observed with therapeutic use of desloratadine. Our data also indicate when administered to a patient with a compromised blood-brain barrier, desloratadine may cause sedation. Patients with compromised cardiovascular systems should be closely monitored when administered desloratadine based on our results that desloratadine has the ability to interfere with normal cardiovascular function mediated by muscarinic receptors.

In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine

PubMed Central

Howell, G; West, L; Jenkins, C; Lineberry, B; Yokum, D; Rockhold, R

2005-01-01

Background Muscarinic receptor mediated adverse effects, such as sedation and xerostomia, significantly hinder the therapeutic usefulness of first generation antihistamines. Therefore, second and third generation antihistamines which effectively antagonize the H1 receptor without significant affinity for muscarinic receptors have been developed. However, both in vitro and in vivo experimentation indicates that the third generation antihistamine, desloratadine, antagonizes muscarinic receptors. To fully examine the in vivo antimuscarinic efficacy of desloratadine, two murine and two rat models were utilized. The murine models sought to determine the efficacy of desloratadine to antagonize muscarinic agonist induced salivation, lacrimation, and tremor. Desloratadine's effect on the cardiovascular system was explored in both rodent models. Results In the pithed rat, both desloratadine (1.0 mg/kg, i.v.) and the muscarinic M2 selective antagonist, methoctramine (0.5 mg/kg, i.v.), inhibited negative inotropic (left ventricular dP/dt) effects caused by oxotremorine, a nonselective muscarinic agonist (p < 0.05). Negative chronotropic effects caused by oxotremorine were inhibited by desloratadine, methoctramine, and the muscarinic M3 selective antagonist, 4-DAMP (1.0 mg/kg, i.v.). A late positive inotropic event observed after the initial decrease was inhibited by all three test compounds with desloratadine and 4-DAMP being the most efficacious. In the conscious animal, inhibition of baroreflex-mediated bradycardia was evaluated. Unlike atropine (0.5 mg/kg, i.v.), desloratadine did not alter this bradycardia. The antimuscarinic action of desloratadine on salivation, lacrimation, and tremor was also explored. In urethane-anesthetized (1.5 g/kg, i.p.) male ICR mice (25–35 g) desloratadine (1.0, 5.0 mg/kg) did not inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, unlike atropine (0.5 mg/kg) and 4-DAMP (1.0 mg/kg). In conscious mice, desloratadine failed to inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, lacrimation, and tremor. However, desloratadine did inhibit oxotremorine-induced tremor in phenylephrine pretreated animals. Conclusion The presented data demonstrate that the third generation antihistamine, desloratadine, does not significantly antagonize peripheral muscarinic receptors mediating salivation and lacrimation, therefore, xerostomia and dry eyes should not be observed with therapeutic use of desloratadine. Our data also indicate when administered to a patient with a compromised blood-brain barrier, desloratadine may cause sedation. Patients with compromised cardiovascular systems should be closely monitored when administered desloratadine based on our results that desloratadine has the ability to interfere with normal cardiovascular function mediated by muscarinic receptors. PMID:16109168

Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transport.

PubMed

Collaco, Anne M; Jakab, Robert L; Hoekstra, Nadia E; Mitchell, Kisha A; Brooks, Amos; Ameen, Nadia A

2013-08-01

The Brunner's glands of the proximal duodenum exert barrier functions through secretion of glycoproteins and antimicrobial peptides. However, ion transporter localization, function, and regulation in the glands are less clear. Mapping the subcellular distribution of transporters is an important step toward elucidating trafficking mechanisms of fluid transport in the gland. The present study examined 1) changes in the distribution of intestinal anion transporters and the aquaporin 5 (AQP5) water channel in rat Brunner's glands following second messenger activation and 2) anion transporter distribution in Brunner's glands from healthy and disease-affected human tissues. Cystic fibrosis transmembrane conductance regulator (CFTR), AQP5, sodium-potassium-coupled chloride cotransporter 1 (NKCC1), sodium-bicarbonate cotransporter (NBCe1), and the proton pump vacuolar ATPase (V-ATPase) were localized to distinct membrane domains and in endosomes at steady state. Carbachol and cAMP redistributed CFTR to the apical membrane. cAMP-dependent recruitment of CFTR to the apical membrane was accompanied by recruitment of AQP5 that was reversed by a PKA inhibitor. cAMP also induced apical trafficking of V-ATPase and redistribution of NKCC1 and NBCe1 to the basolateral membranes. The steady-state distribution of AQP5, CFTR, NBCe1, NKCC1, and V-ATPase in human Brunner's glands from healthy controls, cystic fibrosis, and celiac disease resembled that of rat; however, the distribution profiles were markedly attenuated in the disease-affected duodenum. These data support functional transport of chloride, bicarbonate, water, and protons by second messenger-regulated traffic in mammalian Brunner's glands under physiological and pathophysiological conditions.

Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function

PubMed Central

Concepcion, Axel R.; Vaeth, Martin; Wagner, Larry E.; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P.; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E.; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S.; Cuk, Mario; Yule, David I.

2016-01-01

Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release–activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel–deficient patients and mice with ectodermal tissue–specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice. PMID:27721237

[Long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma].

PubMed

Zhang, Xiangmin; Yu, Lijiang; Wu, Wei; Wu, Xiuhong; Xiao, Fufu; Zeng, Guoxing; Lan, Xiaolin

2013-02-01

To evaluate the long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma. Sixty-five cases of nasopharyngeal carcinoma patients were randomly divided into study group of 32 patients and control group of 33 patents. The submandibular gland was transferred to submental region on 32 cases with nasopharyngeal carcinoma before receiving conventional radiotherapy and a block was used to cover the submental region. Before radiotherapy, two groups of submandibular gland function was detected by imaging of the submandibular gland. At 60 months after radiotherapy, submandibular gland function was detected by 99mTc radionuclide scanning, the questionnaire about the degree of xerostomia was investigated respectively. Five-year survival rate was counted. After following up for 60 months, submandibular gland uptake and secretion function in the study group was significantly higher than that in the control group, there was significant difference between the two groups (P < 0.01) respectively. The incidence of moderate or severe xerostomia in the study group was significantly lower than that in the control group (15.4% vs 76.9%, P < 0.01). Five-year survival rate of the study group and control group was 81.3% and 78.8% respectively, there was no significant difference between the two groups (P > 0.05). The long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma was well. It could improve the quality of life in nasopharyngeal carcinoma patients after radiotherapy, and did not affect the long-term efficacy of nasopharyngeal carcinoma.

Rectal Glands of Marine and Fresh-Water Sharks: Comparative Histology.

PubMed

Oguri, M

1964-05-29

The rectal glands of elasmobranchs perform the function of salt-excreting organs. These glands are smaller and show regressive changes in specimens of the bull shark, Carcharhinus leucas found in fresh-water environment, compared with specimens of this and other species from a marine habitat.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

PubMed

Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

2016-03-15

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

PubMed Central

Paltsev, Michael A.; Polyakova, Victoria O.; Kvetnoy, Igor M.; Anderson, George; Kvetnaia, Tatiana V.; Linkova, Natalia S.; Paltseva, Ekaterina M.; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

2016-01-01

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin A); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

Salivary Gland NK Cells Are Phenotypically and Functionally Unique

PubMed Central

Brossay, Laurent

2011-01-01

Natural killer (NK) cells and CD8+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV). However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV) infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or Treg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells. PMID:21249177

BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands.

PubMed

Alves, Daniel Berretta Moreira; Bingle, Lynne; Bingle, Colin David; Lourenço, Silvia Vanessa; Silva, Andréia Aparecida; Pereira, Débora Lima; Vargas, Pablo Agustin

2017-01-16

The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-.

PubMed

Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

2012-10-31

MAJOR SALIVARY GLANDS OF BOTH HUMANS AND RODENTS CONSIST OF THREE PAIRS OF MACROSCOPIC GLANDS: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638-1686), Thomas Wharton (1614-1673), and Caspar Bartholin (1655-1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.

Structure and Function of Your Skin

MedlinePlus

... the innermost layer. Blood vessels, nerves, hair follicles, oil glands and sweat glands are located in the dermis. What It Does . . . The major function of skin is to provide a barrier between you and the outside environment. Without this protective covering, your life on earth ...

[Serum thyroxine-binding protein for determining the functional state of the thyroid gland in pregnant women with endemic goiter].

PubMed

Korol'kova, O A; Cheremukhin, V I

1975-01-01

A determination was made of the hormone-forming capacity of the thyroid gland in pregnent women under conditions of goiter endemic at various periods of pregnancy by trimesters (123-in healthy pregnant women, 206-with euthyroid goiter of the I degree, 271-or II degree, 90-of the II degree, and 4-of the IV degree). A method of zonal electrophoresis in the medinal-veronal buffer was applied. Thyrofixin with I131 isotope (made in the USSR) was used. With increase of the periods of pregnancy and the degree of euthyroid hyperplasia of the thyroid gland and goiter the thyroid gland function became elevated irrespective of age.

Clinical Management of Salivary Gland Hypofunction and Xerostomia in Head-and-Neck Cancer Patients: Successes and Barriers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vissink, Arjan; Mitchell, James B.; Baum, Bruce J.

The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.

[Clinical characteristics of short tear film breakup time (BUT) -type dry eye].

PubMed

Yamamoto, Yuji; Yokoi, Norihiko; Higashihara, Hisayo; Inagaki, Kayoko; Sonomura, Yukiko; Komuro, Aoi; Kinoshita, Shigeru

2012-12-01

To evaluate the clinical characteristics and management of short tear film breakup time (BUT) -type dry eye. Clinical background and post-treatment changes of symptoms in 77 patients with short BUT -type dry eye were investigated. Treatment consisted of artificial-tear eye-drop instillation and, if necessary, the addition of a low-density-level steroid, hyaluronic acid, a low-density-level cyclopentolate prepared by ourselves and punctal plugs inserted into the upper and lower lacrimal puncta. There were three times more women than men among the patients, and the peak age of occurrence was in the twenties in the men and in the sixties in the women. Our findings show that visual display terminal (VDT) work, contact lens (CL) wear, and changes in the sex hormones may initiate subjective symptoms. Some patients had simultaneous conjunctivochalasis, allergic conjunctivitis, and meibomian gland dysfunction. Nineteen patients (24.7%) were effectively treated with eye-drop instillation alone. Thirty-seven patients (48.1%) required punctal-plug insertion, which was completely effective in only 8 of them (21.6%). Mainly young men and menopausal women contract short BUT -type dry eye. Changes in sex hormones, VDT work and CL wear may be causal, and the disease cannot be controlled by eyedrop and punctal-plug treatment alone.

Ophthalmic manifestations in patients with ectodermal dysplasia syndromes.

PubMed

Keklikci, Ugur; Yavuz, Izzet; Tunik, Selcuk; Ulku, Zelal Baskan; Akdeniz, Sedat

2014-01-01

Ectodermal dysplasia (ED) is a disorder that results from abnormal formation of at least two of the four major ectodermal derivatives in the developing embryo. The ectoderm of the embryo forms the skin, teeth, hair and nails, sweat glands and part of the eyes. The aim of this article is to reveal ophthalmologic symptoms and signs as multidisciplinary, reliable criteria for ectodermal dysplasia. In this retrospective study, 24 patients with ED were analyzed from the recorded data. Ophthalmological examination of the patients, who had previously received the diagnosis of ED in the dental department, was done. During the examination, ocular symptoms related to tear film, corneal changes, lacrimal duct, periorbital hyperpigmentation, alteration lashes and eyebrows were evaluated. The age ranged between 3-45, and the mean and standard deviation (Mean ± SD) was 15.8 ± 7.4 years. The number of males was 13 (54.2%) and females, 11 (45.8%). Eighteen patients (75.0%) suffered from ocular complaints related to the ocular surface. In 11 of the patients with ED, there were dry eye symptoms. While the mean age of cases with eye involvement was 17.5, it was 23.1 in cases with dry eye symptoms. In the study, it was observed that, in patients with ED, ocular complaints, particularly dry eye symptoms, may increase as age advances.

Elevation of autophagy markers in Sjögren syndrome dry eye.

PubMed

Byun, Yong-Soo; Lee, Hyun Jung; Shin, Soojung; Chung, So-Hyang

2017-12-08

Autophagy is known to be implicated in the pathogenesis of Sjögren syndrome (SS), but evidences are limited. We aimed to examine the levels of autophagy markers in tear film and conjunctival epithelial cells from SS dry eye patients, and analyze their correlations with clinical features. Patients with SS dry eye exhibited lower Schirmer values, lower tear breakup time, and higher ocular staining scores. In tears, ATG5 and LC3B-II/I levels were significantly higher in SS dry eye. ATG5 and LC3B-II mRNA in the conjunctiva were also elevated in SS dry eye compared with non-SS dry eye. The immunostaining of conjunctival epithelium showed a punctate pattern of ATG5 and LC3B-II in SS dry eye. These staining patterns were also observed in the lacrimal gland of SS animal models. ATG5 levels in tears and the conjunctival epithelium strongly correlated with ocular staining scores, and one month of topical corticosteroid treatment reduced both ATG5 and LC3B-II/I levels in tear film and the conjunctival epithelium of patients with SS dry eye. Our results suggest that autophagy is enhanced or dysregulated in SS and autophagy markers may be serve as both diagnostic and therapeutic biomarkers in SS dry eye.

Orbital lymphoma masquerading as thyroid ophthalmopathy.

PubMed

Boyce, P J

1998-10-01

Lymphoid tumors are known to originate within the lacrimal gland and orbital fat. Ocular findings commonly seen are a palpable mass with proptosis and downward displacement of the globe. Graves' ophthalmopathy is the most common orbital pathology occurring in the general population. Signs and symptoms of Graves' ophthalmopathy, such as unilateral or bilateral proptosis, double vision, limitation of movement of the extraocular muscles, are not specific for this condition. A 57-year-old man came to us with a chief symptom of "eye swelling" for the last 3 years. He had been diagnosed with hyperthyroidism and had received three surgical procedures for orbital decompression. Clinical findings included limitation of upward and downward gaze, exophthalmometry readings of 30 1/2 mm O.D. and 31 mm O.S. (with a base of 112), and profound proptosis with fatty tissue prolapse. Subsequent thyroid testing revealed euthyroid status and computed tomography scan revealed orbital lymphoma. Orbital involvement from a malignant nodular histiocytic lymphoma resulted in a proptosis similar to that observed in Graves' ophthalmopathy. This very unusual presentation of orbital lymphoma mimicked Graves' disease so closely that the true cause was overlooked. This case emphasizes the need to include space-occupying lesions in the differential diagnosis of proptosis and gaze restrictions. The disease process and controversial management strategies are discussed.

Piezosurgery for osteotomies in orbital surgery: Our experience and review of the literature

PubMed Central

Iacoangeli, Maurizio; Neri, Piergiorgio; Balercia, Paolo; Lupi, Ettore; Di Rienzo, Alessandro; Nocchi, Niccolò; Alvaro, Lorenzo; Scerrati, Massimo

2012-01-01

INTRODUCTION Piezoelectric bone surgery, simply known as Piezosurgery®, is a new promising technique for bone cutting based on ultrasonic microvibrations that allows to perform precise and thin osteotomies with soft tissue sparing. PRESENTATION OF CASE A 45-years-old woman presenting with progressive left ocular pain, diplopia on the lateral left gaze, and visible exophthalmos was admitted to our department. CT scan and MRI images documented a left supero-lateral orbital lesion. A left lateral orbitotomy using the piezoelectric scalpel was performed. The tumour (lacrimal gland lymphoma) was completely removed with no injuries to the orbital structures and with a perfect realignment of the bone stumps. DISCUSSION High powered pneumatic osteotome are commonly used to perform craniotomies. Large bone cutting groove and high temperatures developing at the contact site could produce an uneasy bone healing. The use of a piezoelectric scalpel allows to realize precise and thin osteotomies, facilitating craniotomy's borders ossification and avoiding injuries to non-osseous structures. CONCLUSION Widely used in Oral and Maxillofacial Surgery, Piezosurgery® can also be useful in neurosurgical approaches in order to obtain a faster bone flap re-ossification, a better aesthetic result, and a lower risks of dural layer and soft tissue damage. PMID:23276764

Regulating effect of epithalone on gastric endocrine cells in pinealectomized rats.

PubMed

Khavinson, V K; Popuchiev, V V; Kvetnoii, I M; Yuzhakov, V V; Kotlova, L N

2000-12-01

Endocrine cells in the stomach of pinealectomized rats after injection of epithalone (pineal gland peptide) were studied by immunohistochemical tests, morphometry, and image analysis microscopic images. A functional relationship was found between the pineal gland and stomach, which is regulated by peptides produced by the pineal gland.

Treatment for meibomian gland dysfunction and dry eye symptoms with a single-dose vectored thermal pulsation: a review.

PubMed

Blackie, Caroline A; Carlson, Alan N; Korb, Donald R

2015-07-01

Meibomian gland dysfunction (MGD) is understood to be a highly prevalent, chronic progressive disease and the leading cause of dry eye. All available published peer-reviewed results of the novel vectored thermal pulsation therapy for patients with MGD are investigated. The PubMed and meeting abstract search revealed a total of 31 peer-reviewed reports on vectored thermal pulsation therapy at the time of the search (eight manuscripts and 23 meeting abstracts). All manuscripts evidence a significant increase in meibomian gland function (∼3×) and symptom improvement post a single 12-min treatment. Additional reported objective measures such as osmolarity, tear break-up time, or lipid layer thickness also increased as a result of the therapy; however, not all findings were statistically significant. The randomized controlled studies evidence sustained gland function and symptom relief lasting out to 12 months. The uncontrolled case series evidence significantly longer duration of effect. A single 12 minute vectored thermal pulsation treatment allows for reducing dry eye symptoms, improving meibomian gland function and other correlates of the ocular surface health.

Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway

PubMed Central

Liu, Xibao; Gong, Baijuan; de Souza, Lorena Brito; Ong, Hwei Ling; Subedi, Krishna P.; Cheng, Kwong Tai; Swaim, William; Zheng, Changyu; Mori, Yasuo; Ambudkar, Indu S.

2017-01-01

Store-operated Ca2+ entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3–mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. After irradiation, acinar cells from the submandibular glands of TRPM2+/+, but not those from TRPM2−/− mice, displayed an increase in the concentrations of mitochondrial Ca2+ and reactive oxygen species, a decrease in mitochondrial membrane potential, and activation of caspase-3, which was associated with a sustained decrease in STIM1 abundance and attenuation of SOCE. In a salivary gland cell line, silencing the mitochondrial Ca2+ uniporter or caspase-3 or treatment with inhibitors of TRPM2 or caspase-3 prevented irradiation-induced loss of STIM1 and SOCE. Expression of exogenous STIM1 in the salivary glands of irradiated mice increased SOCE and fluid secretion. We suggest that targeting the mechanisms underlying the loss of STIM1 would be a potentially useful approach for preserving salivary gland function after radiation therapy. PMID:28588080

Human eccrine sweat gland cells turn into melanin-uptaking keratinocytes in dermo-epidermal skin substitutes.

PubMed

Böttcher-Haberzeth, Sophie; Biedermann, Thomas; Pontiggia, Luca; Braziulis, Erik; Schiestl, Clemens; Hendriks, Bart; Eichhoff, Ossia M; Widmer, Daniel S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

2013-02-01

Recently, Biedermann et al. (2010) have demonstrated that human eccrine sweat gland cells can develop a multilayered epidermis. The question still remains whether these cells can fulfill exclusive and very specific functional properties of epidermal keratinocytes, such as the incorporation of melanin, a feature absent in sweat gland cells. We added human melanocytes to eccrine sweat gland cells to let them develop into an epidermal analog in vivo. The interaction between melanocytes and sweat gland-derived keratinocytes was investigated. The following results were gained: (1) macroscopically, a pigmentation of the substitutes was seen 2-3 weeks after transplantation; (2) we confirmed the development of a multilayered, stratified epidermis with melanocytes distributed evenly throughout the basal layer; (3) melanocytic dendrites projected to suprabasal layers; and (4) melanin was observed to be integrated into former eccrine sweat gland cells. These skin substitutes were similar or equal to skin substitutes cultured from human epidermal keratinocytes. The only differences observed were a delay in pigmentation and less melanin uptake. These data suggest that eccrine sweat gland cells can form a functional epidermal melanin unit, thereby providing striking evidence that they can assume one of the most characteristic keratinocyte properties.

Anatomy and Histology of Rodent and Human Major Salivary Glands

PubMed Central

Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

2012-01-01

Major salivary glands of both humans and rodents consist of three pairs of macroscopic glands: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638–1686), Thomas Wharton (1614–1673), and Caspar Bartholin (1655–1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands. The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands. PMID:23209333

Histological characterization of peppermint shrimp ( Lysmata wurdemanni) androgenic gland

NASA Astrophysics Data System (ADS)

Liu, Xin; Zhang, Dong; Lin, Tingting

2017-12-01

The androgenic gland (AG) is an important endocrine gland for male reproductive function in crustaceans. In the present study, we investigated the histological characteristics of the androgenic gland of peppermint shrimp, Lysmata wurdemanni. The peppermint shrimp matures as male first, then some individuals may become euhermaphrodite after several moltings (transitional phase). Euhermaphrodite-phase shrimp acts as male at intermolts. However, it can be fertilized as a female immediately after molting. Considering the male reproductive function acts in its lifespan except for at larval stages, and female reproductive system starts to develop at transitional phase, we hypothesized that AG activity might be reduced to allow and promote vitellogenesis onset in early transitional phase and the following euhermaphrodite phase. So AG cell structure might be different in three phases in L. wurdemanni. The results showed that AG exists in the male in transitional and euhermaphrodite phases. The gland cell clusters surrounding the ejaculatory ducts locate at the roots of the fifth pereopods. The nucleus diameters are similar in the three phases while the nucleus- to-cell ratio is the lowest in euhermaphrodite phase. Our results indicated that for the individuals that will become euhermaphrodite, the cellular structure of AG changes since transitional phase. Male reproductive function which is still available in euhermaphrodite-phase shrimp should be due to the existence of the gland.

Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance.

PubMed

Rath, Martin F; Rohde, Kristian; Klein, David C; Møller, Morten

2013-06-01

The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function. A working model is proposed for understanding the sequential action of homeobox genes in controlling development and mature circadian function of the mammalian pinealocyte based on knowledge from detailed developmental and daily gene expression analyses in rats, the pineal phenotypes of homebox gene-deficient mice and studies on development of the retinal photoreceptor; the pinealocyte and retinal photoreceptor share features not seen in other tissues and are likely to have evolved from the same ancestral photodetector cell.

Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance

PubMed Central

Rath, Martin F.; Rohde, Kristian; Klein, David C.; Møller, Morten

2012-01-01

The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function. A working model is proposed for understanding the sequential action of homeobox genes in controlling development and mature circadian function of the mammalian pinealocyte based on knowledge from detailed developmental and daily gene expression analyses in rats, the pineal phenotypes of homebox gene-deficient mice and studies on development of the retinal photoreceptor; the pinealocyte and retinal photoreceptor share features not seen in other tissues and are likely to have evolved from the same ancestral photodetector cell. PMID:23076630

The epigenetic landscape of mammary gland development and functional differentiation

USDA-ARS?s Scientific Manuscript database

Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

Comparative Study of the Labial Gland Secretion in Termites (Isoptera)

PubMed Central

Sillam-Dussès, David; Krasulová, Jana; Vrkoslav, Vladimír; Pytelková, Jana; Cvačka, Josef; Kutalová, Kateřina; Bourguignon, Thomas; Miura, Toru; Šobotník, Jan

2012-01-01

Labial glands are present in all castes and developmental stages of all termite species. In workers, their secretion contains a food-marking pheromone and digestive enzymes, while soldier secretion plays a defensive role. However, these functions were studied only in a limited set of species, and do not allow drawing general conclusions. Hence, we have investigated the chemical composition of the labial gland extracts from soldiers and workers in 15 termite species belonging to 6 families using an integrative approach based on proteomic and small-molecule profiling. We confirmed the presence of hydroquinone and cellulase in the labial glands of workers, and we identified new toxic compounds in soldiers and workers of several species. Our results highlight the dual role of labial gland secretion, i.e. the defensive role in soldiers and workers of several termite species, and the digestive function in workers. PMID:23071569

Comparative study of the labial gland secretion in termites (Isoptera).

PubMed

Sillam-Dussès, David; Krasulová, Jana; Vrkoslav, Vladimír; Pytelková, Jana; Cvačka, Josef; Kutalová, Kateřina; Bourguignon, Thomas; Miura, Toru; Šobotník, Jan

2012-01-01

Labial glands are present in all castes and developmental stages of all termite species. In workers, their secretion contains a food-marking pheromone and digestive enzymes, while soldier secretion plays a defensive role. However, these functions were studied only in a limited set of species, and do not allow drawing general conclusions. Hence, we have investigated the chemical composition of the labial gland extracts from soldiers and workers in 15 termite species belonging to 6 families using an integrative approach based on proteomic and small-molecule profiling. We confirmed the presence of hydroquinone and cellulase in the labial glands of workers, and we identified new toxic compounds in soldiers and workers of several species. Our results highlight the dual role of labial gland secretion, i.e. the defensive role in soldiers and workers of several termite species, and the digestive function in workers.

Establishment of functional acinar-like cultures from human salivary glands.

PubMed

Jang, S I; Ong, H L; Gallo, A; Liu, X; Illei, G; Alevizos, I

2015-02-01

Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers-namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients. © International & American Associations for Dental Research 2014.

A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse.

PubMed

Rohde, Kristian; Bering, Tenna; Furukawa, Takahisa; Rath, Martin Fredensborg

2017-10-01

The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential for pineal gland development. In contrast, deletion of Rax in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required for the nucleus to develop. Telemetric analyses confirmed the lack of a functional circadian clock. Arylalkylamine N-acetyltransferase (Aanat) transcripts, encoding the melatonin rhythm-generating enzyme, were undetectable in the pineal gland of the Rax conditional knockout under normal conditions, whereas the paired box 6 homeobox gene, known to regulate pineal development, was up-regulated. By injecting isoproterenol, which mimics a nocturnal situation in the pineal gland, we were able to induce pineal expression of Aanat in the Rax conditional knockout mouse, but Aanat transcript levels were significantly lower than those of Rax-proficient mice. Our data suggest that Rax controls pineal gene expression and via Aanat may modulate melatonin synthesis. © 2017 International Society for Neurochemistry.

Dissecting the Functions of Autophagy in Breast Cancer-Associated Fibroblasts

DTIC Science & Technology

2015-10-01

normally provide structural integrity and extracellular matrix remodeling required for proper mammary gland development, transition to an “activated...autophagy deficient MMFs into the “cleared” mammary glands of C57B/6 mice. Clearing the mammary gland (removing the mammary epithelium ) allows the...right 4th inguinal mammary gland of each female is cleared of mammary epithelium and 500,000 MMFs, either autophagy competent (lsl-RFP+/+;AdCre) or

Functional Involvement of Carbonic Anhydrase in the Lysosomal Response to Cadmium Exposure in Mytilus galloprovincialis Digestive Gland

PubMed Central

Caricato, Roberto; Giordano, M. Elena; Schettino, Trifone; Lionetto, M. Giulia

2018-01-01

Carbonic anhydrase (CA) is a ubiquitous metalloenzyme, whose functions in animals span from respiration to pH homeostasis, electrolyte transport, calcification, and biosynthetic reactions. CA is sensitive to trace metals in a number of species. In mussels, a previous study demonstrated CA activity and protein expression to be enhanced in digestive gland by cadmium exposure. The aim of the present work was to investigate the functional meaning, if any, of this response. To this end the study addressed the possible involvement of CA in the lysosomal system response of digestive gland cells to metal exposure. The in vivo exposure to acetazolamide, specific CA inhibitor, significantly inhibited the acidification of the lysosomal compartment in the digestive gland cells charged with the acidotropic probe LysoSensor Green D-189, demonstrating in vivo the physiological contribution of CA to the acidification of the lysosomes. Under CdCl2 exposure, CA activity significantly increased in parallel to the increase of the fluorescence of LysoSensor Green charged cells, which is in turn indicative of proliferation and/or increase in size of lysosomes. Acetazolamide exposure was able to completely inhibit the cadmium induced Lysosensor fluorescence increase in digestive gland cells. In conclusion, our results demonstrated the functional role of CA in the lysosomal acidification of Mytilus galloprovincialis digestive gland and its involvement in the lysosomal activation following cadmium exposure. CA induction could physiologically respond to a prolonged increased requirement of H+ for supporting lysosomal acidification during lysosomal activation. PMID:29670538

Adrenal Function Status in Patients with Paracoccidioidomycosis after Prolonged Post-Therapy Follow-Up

PubMed Central

Tobón, Angela M.; Agudelo, Carlos A.; Restrepo, Carlos A.; Villa, Carlos A.; Quiceno, William; Estrada, Santiago; Restrepo, Angela

2010-01-01

This study assessed adrenal function in patients with paracoccididioidomycosis who had been treated to determine a possible connection between high antibody titers and adrenal dysfunction attributable to persistence of the fungus in adrenal gland. Adrenal gland function was studied in 28 previously treated patients, 2 (7.1%) of whom were shown to have adrenal insufficiency and 7 (259%) who showed a below normal response to stimuli by adrenocorticotropic hormone. Paracoccidioides brasiliensis was detected in the adrenal gland from one of the patients with adrenal insufficiency. Although the study failed to demonstrate a significant difference between high antibody titers and low cortisol levels, the proportion of adrenal insufficiency detected and the subnormal response to adrenocorticotropic hormone confirmed that adrenal damage is an important sequela of paracoccidioidomycosis. Studies with a larger number of patients should be conducted to confirm the hypothesis of persistence of P. brasiliensis in adrenal gland after therapy. PMID:20595488

Comparative Analysis of the miRNome of Bovine Milk Fat, Whey and Cells.

PubMed

Li, Ran; Dudemaine, Pier-Luc; Zhao, Xin; Lei, Chuzhao; Ibeagha-Awemu, Eveline Mengwi

2016-01-01

Abundant miRNAs have been identified in milk and mammary gland tissues of different species. Typically, RNA in milk can be extracted from different fractions including fat, whey and cells and the mRNA transcriptome of milk could serve as an indicator of the transcriptome of mammary gland tissue. However, it has not been adequately validated if the miRNA transcriptome of any milk fraction could be representative of that of mammary gland tissue. The objectives of this study were to (1) characterize the miRNA expression spectra from three milk fractions- fat, whey and cells; (2) compare miRNome profiles of milk fractions (fat, whey and cells) with mammary gland tissue miRNome, and (3) determine which milk fraction miRNome profile could be a better representative of the miRNome profile of mammary gland tissue. Milk from four healthy Canadian Holstein cows in mid lactation was collected and fractionated. Total RNA extracted from each fraction was used for library preparation followed by small RNA sequencing. In addition, miRNA transcripts of mammary gland tissues from twelve Holstein cows in our previous study were used to compare our data. We identified 210, 200 and 249 known miRNAs from milk fat, whey and cells, respectively, with 188 universally expressed in the three fractions. In addition, 33, 31 and 36 novel miRNAs from milk fat, whey and cells were identified, with 28 common in the three fractions. Among 20 most highly expressed miRNAs in each fraction, 14 were expressed in common and 11 were further shared with mammary gland tissue. The three milk fractions demonstrated a clear separation from each other using a hierarchical cluster analysis with milk fat and whey being most closely related. The miRNome correlation between milk fat and mammary gland tissue (rmean = 0.866) was significantly higher than the other two pairs (p < 0.01), whey/mammary gland tissue (rmean = 0.755) and milk cell/mammary gland tissue (rmean = 0.75), suggesting that milk fat could be an alternative non-invasive source of RNA in assessing miRNA activities in bovine mammary gland. Predicted target genes (1802) of 14 highly expressed miRNAs in milk fractions were enriched in fundamental cellular functions, infection, organ and tissue development. Furthermore, some miRNAs were highly enriched (FDR <0.05) in milk whey (3), cells (11) and mammary gland tissue (14) suggesting specific regulatory functions in the various fractions. In conclusion, we have obtained a comprehensive miRNA profile of the different milk fractions using high throughput sequencing. Our comparative analysis showed that miRNAs from milk fat accurately portrayed the miRNome of mammary gland tissue. Functional annotation of the top expressed miRNAs in milk confirmed their critical regulatory roles in mammary gland functions and potentially to milk recipients.

Comparative Analysis of the miRNome of Bovine Milk Fat, Whey and Cells

PubMed Central

Li, Ran; Dudemaine, Pier-Luc; Zhao, Xin; Lei, Chuzhao; Ibeagha-Awemu, Eveline Mengwi

2016-01-01

Abundant miRNAs have been identified in milk and mammary gland tissues of different species. Typically, RNA in milk can be extracted from different fractions including fat, whey and cells and the mRNA transcriptome of milk could serve as an indicator of the transcriptome of mammary gland tissue. However, it has not been adequately validated if the miRNA transcriptome of any milk fraction could be representative of that of mammary gland tissue. The objectives of this study were to (1) characterize the miRNA expression spectra from three milk fractions- fat, whey and cells; (2) compare miRNome profiles of milk fractions (fat, whey and cells) with mammary gland tissue miRNome, and (3) determine which milk fraction miRNome profile could be a better representative of the miRNome profile of mammary gland tissue. Milk from four healthy Canadian Holstein cows in mid lactation was collected and fractionated. Total RNA extracted from each fraction was used for library preparation followed by small RNA sequencing. In addition, miRNA transcripts of mammary gland tissues from twelve Holstein cows in our previous study were used to compare our data. We identified 210, 200 and 249 known miRNAs from milk fat, whey and cells, respectively, with 188 universally expressed in the three fractions. In addition, 33, 31 and 36 novel miRNAs from milk fat, whey and cells were identified, with 28 common in the three fractions. Among 20 most highly expressed miRNAs in each fraction, 14 were expressed in common and 11 were further shared with mammary gland tissue. The three milk fractions demonstrated a clear separation from each other using a hierarchical cluster analysis with milk fat and whey being most closely related. The miRNome correlation between milk fat and mammary gland tissue (rmean = 0.866) was significantly higher than the other two pairs (p < 0.01), whey/mammary gland tissue (rmean = 0.755) and milk cell/mammary gland tissue (rmean = 0.75), suggesting that milk fat could be an alternative non-invasive source of RNA in assessing miRNA activities in bovine mammary gland. Predicted target genes (1802) of 14 highly expressed miRNAs in milk fractions were enriched in fundamental cellular functions, infection, organ and tissue development. Furthermore, some miRNAs were highly enriched (FDR <0.05) in milk whey (3), cells (11) and mammary gland tissue (14) suggesting specific regulatory functions in the various fractions. In conclusion, we have obtained a comprehensive miRNA profile of the different milk fractions using high throughput sequencing. Our comparative analysis showed that miRNAs from milk fat accurately portrayed the miRNome of mammary gland tissue. Functional annotation of the top expressed miRNAs in milk confirmed their critical regulatory roles in mammary gland functions and potentially to milk recipients. PMID:27100870

Topical administration of Esculetin as a potential therapy for experimental dry eye syndrome.

PubMed

Jiang, D; Liu, X; Hu, J

2017-12-01

PurposeIn this study, we investigated the therapeutic effects of topical Esculetin for dry eye rabbits through the ocular tests, inflammatory factor levels and specific phosphorylated protein expressions of ERK1/2 singnal pathway.Patients and methodsThirty-two healthy adult male New Zealand white rabbits were chosen for the study. DES models were established after removing of the main lacrimal gland, Harderian gland and nictitating membrane in the left eyes and randomly divided into group DES control, group CsA, group Esculetin and group Esculetin combined with CsA (C&E), meanwhile the right eyes served as group Normal control. Schirmer's I tests, fluorescein scores, goblet cell densities, inflammatory cytokines IL-1α,IL-1β,TNF-αlevels were observed by slit-lamp microscope, conjunctival impression cytology and ELISA essay at week 0, 1, 2, 4, 8. Phosphorylated-ERK1/2 expressions were detected in Western blot analysis at week 8.ResultsAfter induction of DES, aqueous tear production and goblet cell density were decreased, FL score was much higher in group DES control throughout the study (P<0.05). Both topical Esculetin and Esculetin combing CsA increased the SIT values (10±1 mm, 14±3 mm, P<0.05) and goblet cell densities (77±12/HP, 92±12/HP, P<0.05), decreased FL scores (7.48±0.33, 5.09±0.24, P<0.05) at week 8. Alternations of IL-1α,IL-1β,TNF-αlevels had similar trend. In Western blot analysis, downregulations of p-ERK1/2 were observed in therapy groups when compared with group DES control and the most decreasing was found in group C&E (P<0.05).ConclusionTopical Esculetin improved DES symptoms, downregulated the inflammatory cytokine expressions, suppressed the ERK1/2 pathway and enhanced the therapeutic effect of CsA.

Immunolocalization and distribution of functional temperature-sensitive TRP channels in salivary glands.

PubMed

Sobhan, Ubaidus; Sato, Masaki; Shinomiya, Takashi; Okubo, Migiwa; Tsumura, Maki; Muramatsu, Takashi; Kawaguchi, Mitsuru; Tazaki, Masakazu; Shibukawa, Yoshiyuki

2013-11-01

Transient receptor potential (TRP) cation channels are unique cellular sensors involved in multiple cellular functions. Their role in salivary secretion remains to be elucidated. The expression and localization of temperature-sensitive TRP channels in salivary (submandibular, sublingual and parotid) glands were analyzed by immunohistochemistry and quantitative real-time reverse transcription plus the polymerase chain reaction (RT-PCR). The effects of various TRP channel agonists on carbachol (CCh)-induced salivary secretion in the submandibular gland and on the intracellular Ca(2+) concentration ([Ca(2+)]i) in a submandibular epithelial cell line were also investigated. Immunohistochemistry revealed the expression of TRP-melastatin subfamily member 8 (TRPM8) and TRP-ankyrin subfamily member 1 (TRPA1) in myoepithelial, acinar and ductal cells in the sublingual, submandibular and parotid glands. In addition, TRP-vanilloid subfamily member 1 (TRPV1), TRPV3 and TRPV4 were also expressed in myoepithelial, acinar and ductal cells in all three types of gland. Quantitative real-time RT-PCR results demonstrated the mRNA expression of TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1 in acinar and ductal cells in these salivary glands. Perfusion of the entire submandibular gland with the TRPV1 agonist capsaicin (1 μM) via the submandibular artery significantly increased CCh-induced salivation, whereas perfusion with TRPM8 and TRPA1 agonists (0.5 μM WS12 and 100 μM allyl isothiocyanate) decreased it. Application of agonists for each of the thermosensitive TRP channels increased [Ca(2+)]i in a submandibular epithelial cell line. These results indicate that temperature-sensitive TRP channels are localized and distributed in acinar, ductal and myoepithelial cells in salivary glands and that they play a functional role in the regulation and/or modulation of salivary secretion.

Molecular Mechanism of Pancreatic and Salivary Glands Fluid and HCO3− Secretion

PubMed Central

Lee, Min Goo; Ohana, Ehud; Park, Hyun Woo; Yang, Dongki; Muallem, Shmuel

2013-01-01

Fluid and HCO3− secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO3− secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren’s syndrome and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO3− secretion, in particular by secretory glands. Fluid and HCO3− secretion by secretory glands is a two step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl− and secrete HCO3−. The relative volume secreted by acinar and duct cells and modification of electrolyte composition of the secreted fluids varies among secretory glands to meet their physiological functions. In the pancreas, acinar cells secrete small amount of NaCl-rich fluid, while the duct absorbs the Cl− and secretes HCO3− and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO3− secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that contains high concentrations of Na+ and Cl− and fluid secretion is mediated by active Cl− secretion. The salivary glands duct absorbs both the Na+ and Cl− and secretes K+ and HCO3−. In this review, we focus on the molecular mechanism of fluid and HCO3− secretion by the pancreas and salivary glands, to highlight the similarities of the fundamental mechanisms of acinar and duct cell functions, and point the differences to meet glands specific secretions. PMID:22298651

Surgical correction of severe strabismus and enophthalmos secondary to zygomatic arch fracture in a dog.

PubMed

Konrade, Kricket A; Clode, Alison B; Michau, Tammy M; Roe, Simon C; Trumpatori, Brian J; Krug, William V; Gilger, Brian C

2009-01-01

A grossly displaced segmental zygomatic arch fracture with marked ventro-lateral deviation of the left globe was diagnosed in a 3-month-old male German Shepherd dog following a bite injury. The fracture was approached via a modified lateral orbitotomy and a fragment of the lacrimal bone removed. The rostral portion of the fracture was stabilized with a 5-hole 2.0 dynamic compression plate bone plate. The surgical correction achieved sufficient skeletal fixation for proper anatomical reduction of the globe and excellent cosmetic and functional outcomes.

De novo epidermal regeneration using human eccrine sweat gland cells: higher competence of secretory over absorptive cells.

PubMed

Pontiggia, Luca; Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Oliveira, Carol; Braziulis, Erik; Klar, Agnieszka S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

2014-06-01

In our previous work, we showed that human sweat gland-derived epithelial cells represent an alternative source of keratinocytes to grow a near normal autologous epidermis. The role of subtypes of sweat gland cells in epidermal regeneration and maintenance remained unclear. In this study, we compare the regenerative potential of both secretory and absorptive sweat gland cell subpopulations. We demonstrate the superiority of secretory over absorptive cells in forming a new epidermis on two levels: first, the proliferative and colony-forming efficiencies in vitro are significantly higher for secretory cells (SCs), and second, SCs show a higher frequency of successful epidermis formation as well as an increase in the thickness of the formed epidermis in the in vitro and in vivo functional analyses using a 3D dermo-epidermal skin model. However, the ability of forming functional skin substitutes is not limited to SCs, which supports the hypothesis that multiple subtypes of sweat gland epithelial cells hold regenerative properties, while the existence and exact localization of a keratinocyte stem cell population in the human eccrine sweat gland remain elusive.

Outcomes of malignant tumors of the lacrimal apparatus: the University of Texas MD Anderson Cancer Center experience.

PubMed

Skinner, Heath D; Garden, Adam S; Rosenthal, David I; Ang, K Kian; Morrison, William H; Esmaeli, Bita; Pinnix, Chelsea C; Frank, Steven J

2011-06-15

Malignant epithelial neoplasms of the lacrimal apparatus are rare and are typically treated with surgery and occasionally adjuvant radiation therapy (RT). The purpose of this study was to assess treatment outcomes by type of surgery (orbital exenteration vs eye-sparing surgery) and clarify the role of adjuvant RT for this rare disease. Forty-six patients with malignant epithelial neoplasms of the lacrimal apparatus were treated at a single institution from 1945 through 2008. Twenty-seven patients (59%) were treated with orbital exenteration and 19 (41%) with eye-sparing surgery; 64% of the orbital exenteration group and 83% of the eye-sparing surgery group also received adjuvant RT (median dose, 60 grays). Median follow-up time for all patients was 38 months (range, 3-460 months). For the orbital exenteration and eye-sparing surgery groups, the 5-year overall survival (OS) rates were 59% and 62%, and the 5-year disease-free survival (DFS) rates were 49% and 39%, respectively (P = .56, P = .35). Tumor status (T1-2 vs T3-4) was associated with OS (P = .02), and tumor size (<3.5 vs >3.5 cm) with DFS (P = .015). Median time to locoregional recurrence was 85 months for orbital exenteration, and 123 months for eye-sparing surgery. All patients who did not receive RT experienced local recurrence, and RT extended time to locoregional recurrence (median 460 vs 30 months, P = .009). Seven grade ≥3 complications were experienced after adjuvant RT. For appropriately selected patients, an eye-sparing surgery for lacrimal apparatus tumors can achieve similar survival outcomes to those in patients treated with an orbital exenteration. Adjuvant RT should be considered for all patients presenting with these rare tumors. Copyright © 2011 American Cancer Society.

Results of the application of intraoperative mitomycin C in dacryocystorhinostomy.

PubMed

Roozitalab, M H; Amirahmadi, M; Namazi, M R

2004-01-01

Dacryocystorhinostomy (DCR) is widely accepted as the procedure of choice for surgical correction of lacrimal drainage system obstruction distal to common canaliculus in adulthood. The success rate of DCR has been reported to be from 63% to 99%. DCR failure has been attributed to membranous occlusion of the rhinostomy site caused by soft tissue scarring. More recently, use of mitomycin C (MMC) has been described in lacrimal drainage surgery. The beneficial effect of MMC as a surgical adjunct is thought to be related to its potent inhibition of fibroblast proliferation. To improve the success rate of DCR, the authors used MMC as an adjunct to surgery in 130 patients with nasolacrimal duct obstruction undergoing lacrimal surgery. They were assigned randomly into a MMC DCR group and a regular DCR group (control group). The mean age of the MMC group was 40+/-15 years and that of the control group was 42+/-16 years. The standard surgical techniques of an external DCR were used in all patients of both groups. Patients were followed for 6 months. The authors evaluated the patients with subjective symptoms (improvement in tearing) and objective findings such as the height of tear meniscus, fluorescein dye test, and patency at the time of irrigation. There was no significant difference in the age between the two groups (p=1.00). Six patients in the mitomycin group were symptomatic after 6 months' follow-up; probe and irrigation showed non-patency of lacrimal system. The success rate in the MMC group was therefore 90.5% (59/65), and in the conventional group it was 92.4% (60/65). No significant difference between the two groups was present (p=0.75). The authors conclude that the use of intraoperative MMC in DCR surgery does not change the success rate of this procedure.

Immunohistochemical localization of fatty acid transporters and MCT1 in the sebaceous glands of mouse skin.

PubMed

Zheng, Miao; Lee, Shinhye; Tsuzuki, Satoshi; Inoue, Kazuo; Masuda, Daisaku; Yamashita, Shizuya; Iwanaga, Toshihiko

2016-01-01

The sebaceous glands secrete sebum to protect the epidermis and hairs by the oily products. The glands express several transporters and binding proteins for the production of fatty acids and uptake of their sources. The present immunohistochemical study examined the expression and localization of CD36, MCT1, FATP4, and E-FABP in the sebaceous glands, including the meibomian and preputial glands of mice. CD36 and MCT1 in sebaceous glands were largely co-localized along the plasma membrane of secretory cells, while they were separately expressed in the glandular portion of meibomian and preputial glands. Immunoreactivities for FATP4 and E-FABP appeared diffusely in the cytoplasm of secretory cells. Genetic deletion of CD36 did not affect the immunolocalization of the three other molecules. The sebaceous glands were judged to be useful for analyzing the functions and relation of fatty acid transporters and binding proteins.

Clinical management of salivary gland hypofunction and xerostomia in head and neck cancer patients: successes and barriers*

PubMed Central

Vissink, Arjan; Mitchell, James B; Baum, Bruce J; Limesand, Kirsten H; Jensen, Siri Beier; Fox, Philip C; Elting, Linda S; Langendijk, Johannes A; Coppes, Robert P; Reyland, Mary E

2010-01-01

The most significant long-term complication of radiotherapy in the head and neck region is hyposalivation and its related complaints, particularily xerostomia. This paper addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to: (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy. PMID:20970030

[Effect of space flight aboard "Kosmos-1129" on thyroid hormone content of the blood and thyroid gland of rats].

PubMed

Tigranian, R A; Kalita, N F; Makho, L; Langer, P; Knopp, Ia

1985-01-01

Thyrotrophin, thyroxine, triiodothyronine, and reverse triiodothyronine were measured in plasma and thyroxine and triiodothyronine in the thyroid gland of the rats flown for 18.5 days onboard Cosmos-1129. Postflight the plasma content of thyrotrophin and triiodothyronine increased and that of thyroxine decreased and the gland content of thyroxine and triiodothyronine diminished. It is postulated that in the flight animals the functional activity of the thyroid gland declined.

Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland.

PubMed

Tran, Simon D; Sugito, Takayuki; Dipasquale, Giovanni; Cotrim, Ana P; Bandyopadhyay, Bidhan C; Riddle, Kathryn; Mooney, David; Kok, Marc R; Chiorini, John A; Baum, Bruce J

2006-10-01

There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sjögren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na(+)/K(+)-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland.

A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer.

PubMed

Nakayama, Michihiro; Okizaki, Atsutaka; Takahashi, Koji

2016-01-01

Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC). Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n = 35) and a control group (group B, n = 36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A ( P < 0.05). In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A ( P < 0.05). Conclusion. Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968.

A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer

PubMed Central

Okizaki, Atsutaka; Takahashi, Koji

2016-01-01

Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC). Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n = 35) and a control group (group B, n = 36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A (P < 0.05). In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A (P < 0.05). Conclusion. Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968. PMID:28042578

A Deep Insight into the Sialome of Male and Female Aedes aegypti Mosquitoes

PubMed Central

Ribeiro, José M. C.; Martin-Martin, Ines; Arcà, Bruno; Calvo, Eric

2016-01-01

Only adult female mosquitoes feed on blood, while both genders take sugar meals. Accordingly, several compounds associated with blood feeding (i.e. vasodilators, anti-clotting, anti-platelets) are found only in female glands, while enzymes associated with sugar feeding or antimicrobials (such as lysozyme) are found in the glands of both sexes. We performed de novo assembly of reads from adult Aedes aegypti female and male salivary gland libraries (285 and 90 million reads, respectively). By mapping back the reads to the assembled contigs, plus mapping the reads from a publicly available Ae. aegypti library from adult whole bodies, we identified 360 transcripts (including splice variants and alleles) overexpressed tenfold or more in the glands when compared to whole bodies. Moreover, among these, 207 were overexpressed fivefold or more in female vs. male salivary glands, 85 were near equally expressed and 68 were overexpressed in male glands. We call in particular the attention to C-type lectins, angiopoietins, female-specific Antigen 5, the 9.7 kDa, 12–14 kDa, 23.5 kDa, 62/34 kDa, 4.2 kDa, proline-rich peptide, SG8, 8.7 kDa family and SGS fragments: these polypeptides are all of unknown function, but due to their overexpression in female salivary glands and putative secretory nature they are expected to affect host physiology. We have also found many transposons (some of which novel) and several endogenous viral transcripts (probably acquired by horizontal transfer) which are overexpressed in the salivary glands and may play some role in tissue-specific gene regulation or represent a mechanism of virus interference. This work contributes to a near definitive catalog of male and female salivary gland transcripts from Ae. aegypti, which will help to direct further studies aiming at the functional characterization of the many transcripts with unknown function and the understanding of their role in vector-host interaction and pathogen transmission. PMID:26999592

A Little CFTR Goes a Long Way: CFTR-Dependent Sweat Secretion from G551D and R117H-5T Cystic Fibrosis Subjects Taking Ivacaftor

PubMed Central

Char, Jessica E.; Wolfe, Marlene H.; Cho, Hyung-ju; Park, Il-Ho; Jeong, Jin Hyeok; Frisbee, Eric; Dunn, Colleen; Davies, Zoe; Milla, Carlos; Moss, Richard B.; Thomas, Ewart A. C.; Wine, Jeffrey J.

2014-01-01

To determine if oral dosing with the CFTR-potentiator ivacaftor (VX-770, Kalydeco) improves CFTR-dependent sweating in CF subjects carrying G551D or R117H-5T mutations, we optically measured sweat secretion from 32–143 individually identified glands in each of 8 CF subjects; 6 F508del/G551D, one G551D/R117H-5T, and one I507del/R117H-5T. Two subjects were tested only (−) ivacaftor, 3 only (+) ivacaftor and 3 (+/−) ivacaftor (1–5 tests per condition). The total number of gland measurements was 852 (−) ivacaftor and 906 (+) ivacaftor. A healthy control was tested 4 times (51 glands). For each gland we measured both CFTR-independent (M-sweat) and CFTR-dependent (C-sweat); C-sweat was stimulated with a β-adrenergic cocktail that elevated [cAMP]i while blocking muscarinic receptors. Absent ivacaftor, almost all CF glands produced M-sweat on all tests, but only 1/593 glands produced C-sweat (10 tests, 5 subjects). By contrast, 6/6 subjects (113/342 glands) produced C-sweat in the (+) ivacaftor condition, but with large inter-subject differences; 3–74% of glands responded with C/M sweat ratios 0.04%–2.57% of the average WT ratio of 0.265. Sweat volume losses cause proportionally larger underestimates of CFTR function at lower sweat rates. The losses were reduced by measuring C/M ratios in 12 glands from each subject that had the highest M-sweat rates. Remaining losses were estimated from single channel data and used to correct the C/M ratios, giving estimates of CFTR function (+) ivacaftor  = 1.6%–7.7% of the WT average. These estimates are in accord with single channel data and transcript analysis, and suggest that significant clinical benefit can be produced by low levels of CFTR function. PMID:24520399

Class specific peptide inhibitors for secretory phospholipases A2.

PubMed

Mahalka, Ajay K; Kinnunen, Paavo K J

2013-06-28

Phospholipases A2 (PLA2) catalyze the hydrolytic cleavage of free fatty acids from the sn-2 OH-moiety of glycerophospholipids. These enzymes have a number of functions, from digestion to signaling and toxicity of several venoms. They have also been implicated in inflammation and are connected to diverse diseases, such as cancer, ischemia, atherosclerosis, and schizophrenia. Accordingly, there is a keen interest to develop selective inhibitors for therapeutic use. We recently proposed a novel mechanism for the control of PLA2 activity with highly active protofibrils of PLA2 existing transiently before conversion to inactive amyloid fibrils [19]. In keeping with the above mechanism several algorithms identified (85)KMYFNLI(91) and (17)AALSYGFYG(25) in bee venom (bv) and human lacrimal fluid (Lf) PLA2, respectively, as a regions potentially forming amyloid type aggregates. Interestingly, in keeping with the proposed role of these sequences in the control of the activity of these enzymes, preincubation of 2nM bvPLA2 with (85)KMYFNLI(91) caused complete inhibition of PLA2 activity while the scrambled control peptide YNFLIMK had no effect. Approximately 36% attenuation of the hydrolytic activity of LfPLA2 present in human lacrimal fluid was observed in the presence of 80nM (17)AALSYGFYG(25). Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on meibomian gland functionality in patients with lipid deficient/evaporative dry eye.

PubMed

Korb, Donald R; Blackie, Caroline A; Finnemore, Victor M; Douglass, Teresa

2015-04-01

The aim of this study was to assess the efficacy of using a combination treatment approach consisting of lipid emulsion eye drops, eyelid cleansing wipes, and omega-3 vitamin supplements compared with warm compresses in improving meibomian gland functionality in patients with lipid-deficient/evaporative dry eye disease (LDDE). This single-center, open-label, investigator-masked, randomized study enrolled patients aged ≥18 years, clinically diagnosed with LDDE defined as having ≤6 functional meibomian glands [meibomian gland yielding liquid secretion (MGYLS)] and positive for dry eye symptoms at screening. Patients were randomized to receive either the combination treatment (lipid emulsion eye drops, omega-3 supplements, and lid hygiene with eyelid wipes) or to apply warm, wet compresses once daily, 8 minutes per day, for 3 months. Meibomian gland functionality (number of MGYLS; primary outcome) and patient-reported subjective assessments (SPEED and OSDI questionnaires; secondary outcomes) were evaluated. Adverse events (AEs) and visual acuity were assessed as safety endpoints. Mean patient age was 41.7 years (n = 26; n = 13 per group). Mean ± SD number of MGYLS was not statistically significantly different between groups at baseline (combination treatment, 3.5 ± 1.5; warm compresses, 4.2 ± 1.4, P > 0.5), and was significantly greater with combination treatment versus warm compresses after 3 months of treatment (9.3 ± 2.7 vs. 4.7 ± 2.3; P = 0.006). Dry eye symptoms were significantly improved in both groups at all follow-up visits. Two AEs unrelated to treatment were reported; the BCVA was unchanged from baseline in both groups. The combination treatment regimen resulted in significant improvement in meibomian gland functionality and dry eye symptoms. No safety issues were observed.

Odorous secretions in anurans: morphological and functional assessment of serous glands as a source of volatile compounds in the skin of the treefrog Hypsiboas pulchellus (Amphibia: Anura: Hylidae).

PubMed

Brunetti, Andrés E; Hermida, Gladys N; Iurman, Mariana G; Faivovich, Julián

2016-03-01

Serous (granular or venom) glands occur in the skin of almost all species of adult amphibians, and are thought to be the source of a great diversity of chemical compounds. Despite recent advances in their chemistry, odorous volatile substances are compounds that have received less attention, and until now no study has attempted to associate histological data with the presence of these molecules in amphibians, or in any other vertebrate. Given the recent identification of 40 different volatile compounds from the skin secretions of H. pulchellus (a treefrog species that releases a strong odour when handled), we examined the structure, ultrastructure, histochemistry, and distribution of skin glands of this species. Histological analysis from six body regions reveals the presence of two types of glands that differ in their distribution. Mucous glands are homogeneously distributed, whereas serous glands are more numerous in the scapular region. Ultrastructural results indicate that electron-translucent vesicles observed within granules of serous glands are similar to those found in volatile-producing glands from insects and also with lipid vesicles from different organisms. Association among lipids and volatiles is also evidenced from chemical results, which indicate that at least some of the volatile components in H. pulchellus probably originate within the metabolism of fatty acids or the mevalonate pathway. As odorous secretions are often considered to be secreted under stress situations, the release of glandular content was assessed after pharmacological treatments, epinephrine administrated in vivo and on skin explants, and through surface electrical stimulation. Serous glands responded to all treatments, generally through an obvious contraction of myoepithelial cells that surround their secretory portion. No response was observed in mucous glands. Considering these morpho-functional results, along with previous identification of volatiles from H. pulchellus and H. riojanus after electrical stimulation, we suggest that the electron-translucent inclusions found within the granules of serous glands likely are the store sites of volatile compounds and/or their precursors. Histochemical and glandular distribution analyses in five other species of frogs of the hylid tribe Cophomantini, revealed a high lipid content in all the species, whereas a heterogeneous distribution of serous glands is only observed in species of the H. pulchellus group. The distribution pattern of serous glands in members of this species group, and the odorous volatile secretions are probably related to defensive functions. © 2015 Anatomical Society.

Eccrine sweat gland development and sweat secretion

PubMed Central

Cui, Chang-Yi; Schlessinger, David

2017-01-01

Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell-specific Foxa1 expression was shown to regulate a Ca2+-dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers – for example InsP3 and Ca2+ – and downstream ion channels/transporters in the framework of a Na+-K+-Cl− cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid–base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined. PMID:26014472

Hyaluronic Acid Decreases Lipid Synthesis in Sebaceous Glands.

PubMed

Jung, Yu Ra; Hwang, Chul; Ha, Jeong-Min; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Lee, Young; Seo, Young-Joon; Lee, Young-Ho; Kim, Chang-Deok; Lee, Jeung-Hoon; Im, Myung

2017-06-01

Hyaluronic acid (HA) is the major glycosaminoglycan in the extracellular matrix and has been implicated in several functions in skin cells. However, evidence is lacking regarding the HA signaling in sebaceous glands, and its potential role needs to be clarified. We investigated the role of HA in lipid production in sebaceous glands in an experimental study of human sebocytes followed by a clinical study. We first examined the effects of HA on sebaceous glands in hamsters and intradermal injection of HA into hamster auricles decreased both the size of sebaceous glands and the level of lipid production. We demonstrated that human skin sebaceous glands in vivo and sebocytes in vitro express CD44 (HA binding receptor) and that HA downregulates lipid synthesis in a dose-dependent manner. To evaluate the clinical relevance of HA in human skin, 20 oily participants were included in a double-blind, placebo-controlled, split-face study, and the HA-treated side showed a significant decrease in sebum production. The results of this study indicate that HA plays a functional role in human sebaceous gland biology and HA signaling is an effective candidate in the management of disorders in which sebum production is increased. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Hypertensive crisis caused by electrocauterization of the adrenal gland during hepatectomy.

PubMed

Doo, A Ram; Son, Ji-Seon; Han, Young-Jin; Yu, Hee Chul; Ko, Seonghoon

2015-02-14

Hypertensive crisis (i.e., systolic blood pressure over 300 mmHg) is very rare during operation except pheochromocytoma, but it can be a fatal and embarrassing to surgeons and anesthesiologists. The right adrenal gland can be electrocauterized during a right hemi-hepatectomy. We report a case of hypertensive crisis during right hemi-hepatectomy in which the right adrenal gland was stimulated by monopolar electrocautery in a patient with normal neuroendocrine function. A 73-year-old man with hepatocellular carcinoma was scheduled to undergo right hemi-hepatectomy. Three hours into the surgery, the patient's blood pressure increased abruptly from 100/40 to over 350/130 mmHg (the maximum measurement pressure of the monitor; 350 mmHg). The surgeon had cauterized the right adrenal gland using monopolar electrocautery to separate the liver from the adrenal gland immediately prior to the event. Approximately 3 minutes after suspending the operation, blood pressure returned to baseline levels. After the event, the operation was successfully completed without any complication. Hormonal studies and iodine-123 meta-iodobenzylguanidine scintigraphy revealed no neuroendocrine tumor such as a pheochromocytoma. Operations such as hepatectomy that stimulate the adrenal gland may lead to an unexpected catecholamine surge and result in hypertensive crisis, even if neuroendocrine function of the adrenal gland is normal.

Adenovirus-mediated hAQP1 expression in irradiated mouse salivary glands causes recovery of saliva secretion by enhancing acinar cell volume decrease

PubMed Central

Teos, LY; Zheng, C-Y; Liu, X; Swaim, WD; Goldsmith, CM; Cotrim, AP; Baum, BJ; Ambudkar, IS

2017-01-01

Head and neck irradiation (IR) during cancer treatment causes by-stander effects on the salivary glands leading to irreversible loss of saliva secretion. The mechanism underlying loss of fluid secretion is not understood and no adequate therapy is currently available. Delivery of an adenoviral vector encoding human aquaporin-1 (hAQP1) into the salivary glands of human subjects and animal models with radiation-induced salivary hypofunction leads to significant recovery of saliva secretion and symptomatic relief in subjects. To elucidate the mechanism underlying loss of salivary secretion and the basis for AdhAQP1-dependent recovery of salivary gland function we assessed submandibular gland function in control mice and mice 2 and 8 months after treatment with a single 15-Gy dose of IR (delivered to the salivary gland region). Salivary secretion and neurotransmitter-stimulated changes in acinar cell volume, an in vitro read-out for fluid secretion, were monitored. Consistent with the sustained 60% loss of fluid secretion following IR, a carbachol (CCh)-induced decrease in acinar cell volume from the glands of mice post IR was transient and attenuated as compared with that in cells from non-IR age-matched mice. The hAQP1 expression in non-IR mice induced no significant effect on salivary fluid secretion or CCh-stimulated cell volume changes, except in acinar cells from 8-month group where the initial rate of cell shrinkage was increased. Importantly, the expression of hAQP1 in the glands of mice post IR induced recovery of salivary fluid secretion and a volume decrease in acinar cells to levels similar to those in cells from non-IR mice. The initial rates of CCh-stimulated cell volume reduction in acinar cells from hAQP1-expressing glands post IR were similar to those from control cells. Altogether, the data suggest that expression of hAQP1 increases the water permeability of acinar cells, which underlies the recovery of fluid secretion in the salivary glands functionally compromised post IR. PMID:26966862

Ophthalmological outcome after resection of tumors based on the pineal gland.

PubMed

Hart, Michael G; Sarkies, Nicholas J; Santarius, Thomas; Kirollos, Ramez W

2013-08-01

Descriptions of visual dysfunction in pineal gland tumors tend to focus on upward gaze palsy alone. The authors aimed to characterize the nature, incidence, and functional significance of ophthalmological dysfunction after resection of tumors based on the pineal gland. Review of a retrospective case series was performed and included consecutive patients who underwent surgery performed by a consultant neurosurgeon between 2002 and 2011. Only tumors specifically based on the pineal gland were included; tumors encroaching on the pineal gland from other regions were excluded. All patients with visual signs and/or symptoms were reviewed by a specialist consultant neuroophthalmologist to accurately characterize the nature of their deficits. Visual disturbance was defined as visual symptoms caused by a disturbance of ocular motility. A total of 20 patients underwent resection of pineal gland tumors. Complete resection was obtained in 85%, and there were no perioperative deaths. Visual disturbance was present in 35% at presentation; of those who had normal ocular motility preoperatively 82% had normal motility postoperatively. In total, 55% of patients had residual visual disturbance postoperatively. Although upward gaze tended to improve, significant functional deficits remained, particularly with regard to complex convergence and accommodation dysfunction. Prisms were used in 25% but were only ever partially effective. Visual outcome was only related to preoperative visual status and tumor volume (multivariate analysis). Long-term visual morbidity after pineal gland tumor resection is common and leads to significant functional impairment. Improvement in deficits rarely occurs spontaneously, and prisms only have limited effectiveness, probably due to the dynamic nature of supranuclear ocular movement coordination.

Acro-Dermato-Ungual-Lacrimal-Tooth Syndrome: An Uncommon Member of the Ectodermal Dysplasias.

PubMed

Whittington, Adam; Stein, Sarah; Kenner-Bell, Brandi

2016-09-01

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare form of autosomal dominant ectodermal dysplasia due to mutations in the TP63 gene, a locus that has also been implicated in other syndromic forms of ectodermal dysplasia. It shares many phenotypic characteristics with other TP63 gene mutation syndromes, often making an accurate diagnosis difficult. Long-term management and follow-up of the various sequelae of ectodermal dysplasia require an accurate diagnosis. We report a familial case of ADULT syndrome in a daughter, mother, and son and provide a brief review of the clinical characteristics of this syndrome. © 2016 Wiley Periodicals, Inc.

Pseudodacryocystitis: paediatric case series of infected atypical ethmoid air cells masquerading as recurrent dacryocystitis.

PubMed

Mohite, A; Jenyon, T; Manoj, B; Sandramouli, S; Foster, K; Oates, A; McDermott, A-L; Parulekar, M V

2017-04-01

PurposeTo highlight the clinical and surgical considerations in treating patients with apparent recurrent acute dacryocystitis with a patent lacrimal system.MethodsThree children referred to a tertiary unit as recurrent acute dacryocystitis were reviewed retrospectively. Imaging and subsequent surgical intervention revealed the underlying diagnosis.ResultsAll three cases presented with recurrent abscesses in the region of the lacrimal sac that failed to respond to incision and drainage. The lesions were lower and more lateral to the usual location of a sac abscess and closer to the inferior orbital rim. All three cases were found to have patent lacrimal systems on syringing, and all were found to have infected, low-lying, anteriorly placed aberrant ethmoid air cells on computed tomography and magnetic resonance imaging. These were confirmed on subsequent surgical exploration.ConclusionsInfected low-lying ethmoid air cells can mimic dacryocystitis with recurrent abcesses. In cases where a patent nasolacrimal system is demonstrated and a more inferolateral location of the swelling than would be expected in dacryocystitis is seen, imaging is warranted to ensure the appropriate intervention is undertaken. Anterior ethmoidectomy as opposed to dacryocystorhinostomy is the appropriate treatment in these cases.

The defensive secretion of Carabus lefebvrei Dejean 1826 pupa (Coleoptera, Carabidae): gland ultrastructure and chemical identification.

PubMed

Giglio, Anita; Brandmayr, Pietro; Dalpozzo, Renato; Sindona, Giovanni; Tagarelli, Antonio; Talarico, Federica; Brandmayr, Tullia Zetto; Ferrero, Enrico A

2009-05-01

This study documents the defensive function of flavored humor secreted by the abdominal glands of Carabus lefebvrei pupae. The morphology and the ultrastructure of these glands were described and the volatile compounds of glands secretion were identified by gas chromatography/mass spectrometry. The ultrastructure analysis shows an acinose complex formed by about 50 clusters. Each cluster has 20 glandular units and the unit-composed of one secretory and one canal cell lying along a duct-belongs to the class 3 cell type of Quennedey (1998). In the cytoplasm, the secretory cell contains abundant rough endoplasmatic reticula, glycogen granules, numerous mitochondria, and many well-developed Golgi complexes producing electron-dense secretory granules. Mitochondria are large, elongated, and often adjoining electronlucent vesicles. The kind and the origin of secretory granules varying in size and density were discussed. The chemical analysis of the gland secretion revealed the presence of a mixture of low molecular weight terpenes, ketones, aldehydes, alcohols, esters, and carboxylic acids. Monoterpenes, especially linalool, were the major products. We supposed that ketones, aldehydes, alcohols, esters, and carboxylic acids have a deterrent function against the predators and monoterpenes provide a prophylaxis function against pathogens. (c) 2008 Wiley-Liss, Inc.

Human eccrine sweat gland cells reconstitute polarized spheroids when subcutaneously implanted with Matrigel in nude mice.

PubMed

Li, Haihong; Zhang, Mingjun; Chen, Liyun; Li, Xuexue; Zhang, Bingna

2016-10-01

Increasing evidence indicates that maintenance of cell polarity plays a pivotal role in the regulation of glandular homeostasis and function. We examine the markers for polarity at different time points to investigate the formation of cell polarity during 3D reconstitution of eccrine sweat glands. Mixtures of eccrine sweat gland cells and Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 2, 3, 4, 5 and 6 weeks post-implantation, Matrigel plugs were removed and immunostained for basal collagen IV, lateral β-catenin, lateroapical ZO-1 and apical F-actin. The results showed that the cell polarity of the spheroids appeared in sequence. Formation of basal polarity was prior to lateral, apical and lateroapical polarity. Collagen IV was detected basally at 2 weeks, β-catenin laterally and ZO-1 lateroapically at 3 weeks, and F-actin apically at 4 weeks post-implantation. At week 5 and week 6, the localization and the positive percentage of collagen IV, β-catenin, ZO-1 or F-actin in spheroids was similar to that in native eccrine sweat glands. We conclude that the reconstituted 3D eccrine sweat glands are functional or potentially functional.

Leg tendon glands in male bumblebees ( Bombus terrestris): structure, secretion chemistry, and possible functions

NASA Astrophysics Data System (ADS)

Jarau, Stefan; Žáček, Petr; Šobotník, Jan; Vrkoslav, Vladimír; Hadravová, Romana; Coppée, Audrey; Vašíčková, Soňa; Jiroš, Pavel; Valterová, Irena

2012-12-01

Among the large number of exocrine glands described in bees, the tarsal glands were thought to be the source of footprint scent marks. However, recent studies showed that the compounds used for marking by stingless bees are secreted by leg tendon instead of tarsal glands. Here, we report on the structure of leg tendon glands in males of Bombus terrestris, together with a description of the chemical composition of their secretions and respective changes of both during the males' lives. The ultrastructure of leg tendon glands shows that the secretory cells are located in three independent regions, separated from each other by unmodified epidermal cells: in the femur, tibia, and basitarsus. Due to the common site of secretion release, the organ is considered a single secretory gland. The secretion of the leg tendon glands of B. terrestris males differs in its composition from those of workers and queens, in particular by (1) having larger proportions of compounds with longer chain lengths, which we identified as wax esters; and (2) by the lack of certain hydrocarbons (especially long chain dienes). Other differences consist in the distribution of double bond positions in the unsaturated hydrocarbons that are predominantly located at position 9 in males but distributed at seven to nine different positions in the female castes. Double bond positions may change chemical and physical properties of a molecule, which can be recognized by the insects and, thus, may serve to convey specific information. The function of male-specific compounds identified from their tendon glands remains elusive, but several possibilities are discussed.

[Effect of emotional-algesic stress on the hormonal function of thyroid and parathyroid glands].

PubMed

Kuripka, V I; Belokon', L E; Iakushev, V S

1989-01-01

Experiments on 215 Wistar rats have revealed that the state of the endured stress is an essential factor inducing disturbance in functioning of the hypothalamus-adenohypophysis-thyroid gland system accompanied by disturbance in regulation of the thyrotropin and triiodothyronine formation under conditions of myocardium necrosis development.

[Aging of the pineal gland].

PubMed

Khavinson, V Kh; Golubev, A G

2002-01-01

The age-related changes in the pineal gland are functional rather than organic, which makes their correction or prevention more tenable. The amelioration or inhibition of some age-related impairments of the pineal gland were observed with dietary restriction and the use of S-adenosylmethionine or MAO-A inhibitors. A threefold increase in nocturnal melatonin peaks occurs in old rhesus monkeys treated with a synthetic peptide Ala-Glu-Asp-Gly (Epithalon) designed basing on the amino acid content of a pineal peptide extract Epithalamin. Other effects of Epithalon markedly overlap with melatonin effects. Besides life extension in mice and fruit flies, Epithalon effects include the postponing vision loss in Campbell rats with hereditary pigmental dystrophy. A uniting aspect of such a range of activities might be the participation of transcription factors, since they are often highly conservative in evolution and, on the other hand, may be strictly tissue-specific. The targets of Epithalon may include transfactors that in mammals are specific for the pineal gland and retina and exhibit impaired functions in the aged pineal gland.