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Sample records for corneal edema induced

  1. Corneal edema induced by cold in trigeminal nerve palsy

    SciTech Connect

    Thorgaard, G.L.; Holland, E.J.; Krachmer, J.H.

    1987-05-15

    We examined a 34-year-old man who complained of decreased visual acuity in the right eye when exposed to cold environmental temperatures. Although examination at room temperature was unremarkable, he developed prominent unilateral corneal edema of the right eye when placed in a cold room at 4 C. Corneal thickness increased from 525 to 789 microns in the affected eye. Further examination disclosed a right-sided trigeminal nerve palsy. He was eventually found to have a 3 X 2-cm tentorial ridge meningioma on the right.

  2. Oxygen-deficient metabolism and corneal edema

    PubMed Central

    Leung, B.K.; Bonanno, J.A.; Radke, C.J.

    2014-01-01

    Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem–Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

  3. Oxygen-deficient metabolism and corneal edema.

    PubMed

    Leung, B K; Bonanno, J A; Radke, C J

    2011-11-01

    Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem-Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

  4. Transient Corneal Edema is a Predictive Factor for Pseudophakic Cystoid Macular Edema after Uncomplicated Cataract Surgery

    PubMed Central

    Do, Jae Rock; Oh, Jong-Hyun; Chuck, Roy S.

    2015-01-01

    Purpose To report transient corneal edema after phacoemulsification as a predictive factor for the development of pseudophakic cystoid macular edema (PCME). Methods A total of 150 eyes from 150 patients (59 men and 91 women; mean age, 68.0 ± 10.15 years) were analyzed using spectral domain optical coherence tomography 1 week and 5 weeks after routine phacoemulsification cataract surgery. Transient corneal edema detected 1 week after surgery was analyzed to reveal any significant relationship with the development of PCME 5 weeks after surgery. Results Transient corneal edema developed in 17 (11.3%) of 150 eyes 1 week after surgery. A history of diabetes mellitus was significantly associated with development of transient corneal edema (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.41 to 11.54; p = 0.011). Both diabetes mellitus and transient corneal edema were significantly associated with PCME development 5 weeks after surgery (OR, 4.58; 95% CI, 1.56 to 13.43; p = 0.007; and OR, 6.71; CI, 2.05 to 21.95; p = 0.003, respectively). In the 8 eyes with both diabetes mellitus and transient corneal edema, 4 (50%) developed PCME 5 weeks after surgery. Conclusions Transient corneal edema detected 1 week after routine cataract surgery is a predictive factor for development of PCME. Close postoperative observation and intervention is recommended in patients with transient corneal edema. PMID:25646056

  5. Late corneal edema due to retained foldable lens fragment.

    PubMed

    Gokhale, Nikhil S

    2009-01-01

    Late onset of corneal edema after cataract surgery is an unusual complication. We report a case of corneal edema presenting one month after cataract surgery. During implantation of the foldable lens, one haptic of the intraocular lens fractured at the optic haptic junction. This caused lens decentration, necessitating an intraocular lens exchange ten days later. The patient was recovering well but presented again two weeks later with a drop in vision due to corneal edema. A retained haptic of the intraocular lens was seen in the inferior anterior chamber angle. After surgical removal of the retained haptic the corneal edema fully resolved. Retained intraocular lens fragments can cause corneal endothelial damage, which may be reversible with an early diagnosis and intervention. PMID:19384021

  6. Methylene blue-related corneal edema and iris discoloration.

    PubMed

    Timucin, Ozgur Bulent; Karadag, Mehmet Fatih; Aslanci, Mehmet Emin; Baykara, Mehmet

    2016-04-01

    We report the case of a 70-year-old female patient who developed corneal edema and iris discoloration following the inadvertent use of 1% methylene blue instead of 0.025% trypan blue to stain the anterior capsule during cataract phacoemulsification surgery. Copious irrigation was performed upon realization of incorrect dye use. Corneal edema and iris discoloration developed during the early postoperative period and persisted at 24-months follow-up. However, keratoplasty was not required. The intracameral use of 1% methylene blue has a cytotoxic effect on the corneal endothelium and iris epithelium. Copious irrigation for at least 30 min using an anterior chamber maintainer may improve outcomes. PMID:27224079

  7. Hyskon-induced pulmonary edema.

    PubMed

    Mangar, D

    1993-12-01

    Hyskon (32 percent dextran-70) (Hyskon Division, Pharmacia) is used during hysteroscopy to help visualization of the uterine surfaces. Pulmonary edema of an uncertain cause has occurred in many patients. Because this study could not be conducted in humans, we determined if Hyskon caused cardiogenic or non-cardiogenic pulmonary edema in a dog model. Dogs were randomly assigned to receive an infusion of Hyskon or whole blood to sustain left ventricular end-diastolic pressure between 20 and 23 millimeters of mercury for 60 minutes. In dogs receiving blood, there was no protein in the bronchoalveolar lavage before or after blood was given. In the Hyskon group, there was no protein in the bronchoalveolar lavage before Hyskon and 0.6 +/- 1.4 milligrams per deciliter (range of 0.1 to 3.7 milligram per deciliter) after Hyskon. The ratio of bronchoalveolar lavage protein to plasma protein after Hyskon was 8.0 +/- 18.0 percent compared with zero percent in the blood group. Hyskon altered pulmonary microvascular membrane permeability, causing alveolar flooding with plasma proteins and possibly accounting for the deterioration of oxygenation and pulmonary compliance seen in patients. These results suggest a significant noncardiogenic component of Hyskon induced pulmonary edema. PMID:7505487

  8. Corneal toxicity induced by vesicating agents and effective treatment options.

    PubMed

    Goswami, Dinesh G; Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

    The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial cells and rabbit corneal organ culture models with the SM analog nitrogen mustard, which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries. PMID:27327041

  9. Naloxone-induced pulmonary edema.

    PubMed

    Schwartz, J A; Koenigsberg, M D

    1987-11-01

    We present the case of a 68-year-old woman with acute pulmonary edema secondary to the administration of naloxone to reverse an inadvertent narcotic overdose. The patient presented following a 12-hour history of increasingly bizarre behavior and confusion. A total IV dose of 1.6 mg naloxone was administered in an attempt to reverse the suspected overconsumption of a codeine-containing cough suppressant. She immediately became agitated, tachycardic, and diaphoretic; a clinical diagnosis of acute pulmonary edema was made. Following treatment with furosemide, nitroglycerin, and morphine sulfate, the patient recovered completely without further incident. Although naloxone is thought to be a safe drug with few complications, it should not be used indiscriminantly, and the smallest doses necessary to elicit the desired response should be used. PMID:3662194

  10. Olanzapine-induced tender pitting pre-tibial edema.

    PubMed

    Mathan, Kaliaperumal; Muthukrishnan, Venkatesan; Menon, Vikas

    2015-01-01

    Antipsychotic-induced edema is uncommonly encountered in clinical practice. We report a case of tender pitting pre-tibial edema with olanzapine in a woman with no medical comorbidities. The peculiar distribution of edema resulted in diagnostic confusion necessitating specific investigations. Eventually, the edema resolved following complete stoppage of the drug, but caused distress to the patient and the caregiver. PMID:25969664

  11. Edema

    MedlinePlus

    Edema means swelling caused by fluid in your body's tissues. It usually occurs in the feet, ankles ... it can involve your entire body. Causes of edema include Eating too much salt Sunburn Heart failure ...

  12. The Curious Question of Exercise-Induced Pulmonary Edema

    PubMed Central

    Bates, Melissa L.; Farrell, Emily T.; Eldridge, Marlowe W.

    2011-01-01

    The question of whether pulmonary edema develops during exercise on land is controversial. Yet, the development of pulmonary edema during swimming and diving is well established. This paper addresses the current controversies that exist in the field of exercise-induced pulmonary edema on land and with water immersion. It also discusses the mechanisms by which pulmonary edema can develop during land exercise, swimming, and diving and the current gaps in knowledge that exist. Finally, this paper discusses how these fields can continue to advance and the areas where clinical knowledge is lacking. PMID:21660232

  13. Pseudomonas-induced corneal ulcers associated with contaminated eye mascaras.

    PubMed

    Wilson, L A; Ahearn, D G

    1977-07-01

    Seven Pseudomonas-induced corneal ulcers were associated with the use of four brands of mascara contaminated with P. aeruginosa. In laboratory studies, preservative systems of three of the four brands were inadequate in comparison with a control mascara of known antimicrobial activity. If the corneal epithelium is scratched during the application of mascara, particularly if the applicator is old, the cornea should be treated immediately and the mascara cultured to detect Pseudomonas. The high incidence of recurrent corneal ulceration in cases of Pseudomonas-induced keratitis indicates that initial chemotherapy should be intensive and maintained until the lesion stabilizes. PMID:409295

  14. Staphylococcus aureus Blepharitis Associated with Multiple Corneal Stromal Microabscess, Stromal Edema, and Uveitis.

    PubMed

    Boto-de-los-Bueis, Ana; del Hierro Zarzuelo, Almudena; García Perea, Adela; de Pablos, Manuela; Pastora, Natalia; Noval, Susana

    2015-04-01

    We report a case of an immunocompetent woman with atypical marginal keratitis. She presented with recurrent episodes of multiples microabscess distributed in a triangular pattern associated with stromal oedema and anterior chamber uveitis, affecting both eyes, but not simultaneously. The episodes responded to steroid drops, corneal inflammation was coincidental with a worsening of her blepharitis in the affected eye and S. aureus was isolated from the lids. PMID:24410378

  15. Corneal hydrops induced by diabetic ketoacidosis: A case report

    PubMed Central

    Feng, Meiyan; Wang, Chao

    2016-01-01

    To the best of our knowledge, there have been no reports of corneal hydrops associated with diabetic ketoacidosis. The present study first reports a case of a 20-year-old male patient with diabetic ketoacidosis-induced corneal hydrops. The patient exhibited mild hydrops in their left eyelid, which was accompanied by mixed hyperemia, and hazy turbid in a white color was observed in the cornea. To alleviate the corneal hydrops, 5% glucose was administered dropwise to the left eye for 2 h to alleviate the inflammation. Finally, the patient was discharged from the hospital with a satisfactory outcome. PMID:27602094

  16. Escin attenuates cerebral edema induced by acute omethoate poisoning.

    PubMed

    Wang, Tian; Jiang, Na; Han, Bing; Liu, Wenbo; Liu, Tongshen; Fu, Fenghua; Zhao, Delu

    2011-06-01

    Organophosphorus exposure affects different organs such as skeletal muscles, the gastrointestinal tract, liver, lung, and brain. The present experiment aimed to evaluate the effect of escin on cerebral edema induced by acute omethoate poisoning. Sprague-Dawley rats were administered subcutaneously with omethoate at a single dose of 60 mg/kg followed by escin treatment. The results showed that escin reduced the brain water content and the amount of Evans blue in omethoate-poisoned animals. Treatment with escin decreased the levels of tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE₂) in the brain. Escin also alleviated the histopathological change induced by acute omethoate poisoning. The findings demonstrated that escin can attenuate cerebral edema induced by acute omethoate poisoning, and the underlying mechanism was associated with ameliorating the permeability of the blood-brain barrier. PMID:21417632

  17. Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

    PubMed Central

    Umar, Musa Usman; Abdullahi, Aminu Taura

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

  18. Ketamine/Xylazine-Induced Corneal Damage in Mice

    PubMed Central

    Syed, Nasreen A.; Anderson, Michael G.

    2015-01-01

    Purpose We have observed that the commonly used ketamine/xylazine anesthesia mix can induce a focally severe and permanent corneal opacity. The purpose of this study was to establish the clinical and histological features of this deleterious side effect, its sensitivity with respect to age and anesthesia protocol, and approaches for avoiding it. Methods Young C57BL/6J, C57BLKS/J, and SJL/J mice were treated with permutations of anesthesia protocols and compared using slit-lamp exams, optical coherence tomography, histologic analyses, and telemetric measurements of body temperature. Results Ketamine/xylazine induces corneal damage in mice with a variable frequency. Among 12 experimental cohorts, corneal damage associated with ketamine/xylazine was observed in 9 of them. Despite various treatments to avoid corneal dehydration during anesthesia, the frequency of corneas experiencing damage among responding cohorts was 42% (26% inclusive of all cohorts), which is significantly greater than the natural prevalence (5%). The damage was consistent with band keratopathy. It appeared as a white or gray horizontal band located proximal to the pupil and was positive for subepithelial calcium deposition with von Kossa stain. Conclusions The sum of our clinical and histological observations is consistent with ketamine/xylazine-induced band keratopathy in mice. This finding is relevant for mouse studies involving the eye and/or vision-dependent behavioral assays, which would both be prone to artifact without appreciation of the damage caused by ketamine/xylazine anesthesia. Use of yohimbine is suggested as a practical means of avoiding this complication. PMID:26222692

  19. Superficial Anterior Lamellar Keratoplasty (SALK) for Trauma-induced Post Refractive Surgery Corneal Opacity

    PubMed Central

    Ganger, Anita; Tandon, Radhika; Vanathi, M.; Sagar, Pardeep

    2016-01-01

    Purpose: To report a case of post laser in situ keratomileusis (LASIK), nebulomacular corneal opacity following a trauma induced flap dehiscence and was managed with superficial anterior lamellar keratoplasty (SALK). Case Report: A 32-year-old female underwent LASIK 2.5 years back, with a postoperative unaided visual acuity (VA) of 6/6 in both eyes. She was involved in a road traffic accident and sustained blunt trauma to the right eye 5 months before. At the time of presentation, the VA was 1/60 in the right eye. Slit lamp examination revealed flap dehiscence, stromal scar and descemet folds in that eye. There was a small macular scar in the parafoveal area due to a resolved Berlin's edema. SALK was performed in the affected eye. Unaided VA of 6/36 was noted on post- operative day 1. After 4 weeks of SALK surgery, best corrected VA was 6/24. Conclusion: This case highlights that flap adhesions are not very strong even years after LASIK and SALK may be an effective treatment option for post refractive surgery corneal opacities. PMID:27621794

  20. Multipurpose Care Solution–Induced Corneal Surface Disruption and Pseudomonas aeruginosa Internalization in the Rabbit Corneal Epithelium

    PubMed Central

    Posch, Leila C.; Zhu, Meifang; Robertson, Danielle M.

    2014-01-01

    Purpose. To evaluate the effects of a chemically preserved multipurpose contact lens care solution (MPS) on the corneal epithelial surface and Pseudomonas aeruginosa (PA) internalization in the rabbit corneal epithelium. Methods. Rabbits were fit in one eye with a silicone hydrogel lens (balafilcon A) soaked overnight in a borate-buffered MPS (BioTrue). The contralateral eye was fit with a lens removed directly from the blister pack containing borate-buffered saline (control). Lenses were worn for 2 hours. Upon lens removal, corneas were challenged ex vivo with invasive PA strain 6487 and assessed for PA internalization. Ultrastructural changes were assessed using scanning electron (SEM) and transmission electron microscopy (TEM). Results. Scanning electron microscopy showed frank loss of surface epithelium in MPS-exposed eyes, while control eyes exhibited occasional loss of surface membranes but retention of intact junctional borders. Transmission electron microscopy data supported and extended SEM findings, demonstrating the presence of epithelial edema in MPS-treated eyes. There was a 12-fold increase in PA uptake into the corneal epithelium following wear of the MPS-treated lens compared to control (P = 0.008). Conclusions. These data demonstrate that corneal exposure to MPS during lens wear damages the surface epithelium and are consistent with our previous clinical data showing an increase in bacterial binding to exfoliated epithelial cells following MPS use with resultant increased risk for lens-mediated infection. These findings also demonstrate that the PA invasion assay may provide a highly sensitive quantitative metric for assessing the physiological impact of lens-solution biocompatibility on the corneal epithelium. PMID:24876286

  1. Pharmacological characterization of the rat paw edema induced by Bothrops lanceolatus (Fer de lance) venom.

    PubMed

    de Faria L; Antunes, E; Bon, C; de Araújo, A L

    2001-06-01

    The inflammatory response induced by Bothrops lanceolatus venom (BLV) in the rat hind-paw was studied measuring paw edema. Non-heated BLV (75microg/paw) caused a marked paw edema accompanied by intense haemorrhage whereas heated venom (97 degrees C, 30s; 12.5-100microg/paw) produced a dose- and time-dependent non-haemorrhagic edema. The response with heated BLV was maximal within 15min disappearing over 24h. Heated venom was then routinely used at the dose of 75microg/paw. The prostacyclin analogue iloprost (0.1microg/paw) potentiated by 125% the venom-induced edema. The histamine H(1) receptor antagonist mepyramine (6mg/kg) or the serotonin/histamine receptor antagonist cyproheptadine (6mg/kg) partially inhibited BLV-induced edema whereas the combination of both compounds virtually abolished the edema. The lipoxygenase inhibitor BWA4C (10mg/kg), but not the cyclooxygenase inhibitor indomethacin (10mg/kg), significantly inhibited the edema (35% reduction; P<0.05). Dexamethasone (1mg/kg) also markedly (P<0.001) reduced venom-induced edema. The bradykinin B(2) receptor antagonist Hoe 140 (0.6mg/kg) reduced by 30% (P<0.05) the venom induced edema, whereas the angiotensin-converting enzyme inhibitor captopril (300microg/paw) potentiated by 42% (P<0.05) the edema. Bothrops lanceolatus antivenon (anti-BLV) reduced by 28% (P<0.05) the venom-induced edema while intravenous administration of antivenom failed to affect the edema. In conclusion, BLV-induced rat paw edema involves mast cell degranulation causing local release of histamine and serotonin, a phenomenon mediated mainly by kinins and lipoxygenase metabolites. Additionally, the use of a specific Bothrops lanceolatus antivenom, given subplantarily or intravenously, revealed to be little effective to prevent BLV-induced edema. PMID:11137542

  2. Changes in corneal collagen induced by holmium:YAG laser irradiation

    NASA Astrophysics Data System (ADS)

    Timberlake, George T.; Reinke, Martin H.; Miller, Alvin

    1996-05-01

    Holmium:YAG laser thermokeratoplasty corrects hyperopia (farsightedness) by producing small areas of corneal collagen shrinkage that cause the central cornea to bulge outward, increasing optical power. Collagen shrinkage is probably caused by laser-heated corneal water, but details of the shrinkage mechanism are not known. We investigated the shrinkage mechanism by measuring changes in corneal ultrastructure, surface shrinkage, water content, and strength following Ho:YAG laser exposures. Morphological changes in collagen were documented by measurements from electron micrographs. Corneal adhesive strength was determined by measuring tearing force in a plane parallel to the corneal surface. Laser-induced water loss was measured by weighing corneal samples before and after exposure. Corneal surface shrinkage was assessed by photographing the movement of particles on the cornea. Lasered collagen fibrils increased in diameter, lost their orderly arrangement, and appeared `frayed.' The corneal surface contracted toward lasered areas with a maximal shift of approximately 190 micrometers , more than could be explained by a model based on collagen fibril changes. Water loss plays a minor role in corneal shrinkage since corneal samples lost about only about 1.4% of their weight after massive laser exposure. Despite marked changes in collagen structure, corneal adhesive force was unchanged.

  3. Expression and function of fibroblast growth factor-inducible 14 in human corneal myofibroblasts.

    PubMed

    Ebihara, Nobuyuki; Nakayama, Masafumi; Tokura, Tomoko; Ushio, Hiroko; Murakami, Akira

    2009-08-01

    The interaction of fibroblast growth factor-inducible 14 (Fn14) and, its ligand tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to be important in wound healing of tissues. However, to our knowledge, expression and function of Fn14 in corneal myofibroblasts, which have a crucial role in wound healing of corneal stroma, has not been investigated. In this study, we investigated the expression and function of Fn14 in corneal myofibroblasts. Expression of Fn14 protein was assessed by flow cytometry. Corneal myofibroblasts showed strong expression of Fn14 protein, while keratocytes did not. TGF-beta(1) promoted the differentiation of keratocytes into corneal myofibroblasts, and induced Fn14 expression. These data reveal that keratocytes phenotype determines the level of Fn14 expression. ELISA was used to detect chemokines and matrix metalloproteinases in the supernatant of corneal myofibroblasts cultured with or without stimulation by TWEAK and/or TGF-beta(1). TWEAK increased the production of IL-8, MCP-1, and RANTES by corneal myofibroblasts via Fn14. TGF-beta(1) augmented the TWEAK-induced production of these chemokines. TWEAK also increased the production of MMP-1 and -3 by corneal myofibroblasts via Fn14, while TGF-beta(1) inhibited this effect of TWEAK on MMP production. TWEAK-induced phosphorylation of NF-kappaB and MAP kinase in corneal myofibroblasts. Furthermore, TWEAK partially inhibited the differentiation of keratocytes into corneal myofibroblasts promoted by TGF-beta(1). These data suggest that the Fn14/TWEAK system may have several roles in wound healing by corneal myofibroblasts. In the future, modulation of the TWEAK/Fn14 system may become a novel approach for control corneal wound healing. PMID:19344712

  4. PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury.

    PubMed

    Kim, Dae Won; Lee, Sung Ho; Shin, Min Jea; Kim, Kibom; Ku, Sae Kwang; Youn, Jong Kyu; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Son, Ora; Sohn, Eun Jeong; Cho, Sung-Woo; Park, Jong Hoon; Kim, Hyun Ah; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-11-01

    FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI. PMID:25817214

  5. PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury

    PubMed Central

    Kim, Dae Won; Lee, Sung Ho; Shin, Min Jea; Kim, Kibom; Ku, Sae Kwang; Youn, Jong Kyu; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Son, Ora; Sohn, Eun Jeong; Cho, Sung-Woo; Park, Jong Hoon; Kim, Hyun Ah; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-01-01

    FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI. [BMB Reports 2015; 48(11): 618-623] PMID:25817214

  6. Characterization of platelet-activating factor-induced cutaneous edema and erythema in dogs.

    PubMed

    Watanabe, Miwa; Osada, Hironari; Shimizu, Sunao; Goto, Shun; Nagai, Makoto; Shirai, Junsuke; Sasaki, Kazuaki; Shimoda, Minoru; Itoh, Hiroshi; Ohmori, Keitaro

    2016-09-01

    OBJECTIVE To characterize platelet-activating factor (PAF)-induced edema and erythema in the skin of dogs and compare those reactions with histamine-induced cutaneous reactions. ANIMALS 6 healthy Beagles. PROCEDURES Experiments were performed at ≥ 2-week intervals. Each dog received ID injections (5 μg/site) of PAF C16, PAF C18, lyso-PAF, and histamine. Edema (mean diameter) and erythema scores (none, mild, moderate, or severe) were assessed 30 minutes after the injections. Dogs received ID injections of PAF and histamine each with various concentrations of WEB 2086 (PAF receptor antagonist) or underwent ID testing with PAF and histamine before and 3 hours after oral administration of cetirizine hydrochloride or prednisolone (at 2 doses each). RESULTS ID injections of PAF C16 and PAF C18, but not lyso-PAF, induced comparable levels of edema and erythema. The PAF-induced edema and erythema peaked at 30 minutes and lasted for 6 hours after the injection; histamine-induced edema and erythema peaked at 30 minutes and lasted for 3 hours after the injection. Edema sizes and erythema scores were significantly smaller and lower, respectively, for PAF than for histamine. The WEB 2086 inhibited PAF-induced but not histamine-induced edema and erythema. Cetirizine slightly, but significantly, repressed PAF-induced edema and erythema as well as histamine-induced cutaneous reactions. Prednisolone suppressed both PAF-induced and histamine-induced edema and erythema. CONCLUSIONS AND CLINICAL RELEVANCE In canine skin, the duration of PAF-induced inflammation was longer than that of histamine-induced inflammation. The PAF- and histamine-induced cutaneous reactions were effectively suppressed by oral administration of prednisolone. The importance of PAF in dogs with anaphylaxis and allergic disorders warrants further investigation. PMID:27580108

  7. The Correlation Analysis between Corneal Biomechanical Properties and the Surgically Induced Corneal High-Order Aberrations after Small Incision Lenticule Extraction and Femtosecond Laser In Situ Keratomileusis

    PubMed Central

    Wu, Wenjing; Wang, Yan

    2015-01-01

    Background. To investigate the correlation between corneal biomechanics and the surgically induced corneal high-order aberrations (HOAs) after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). Methods. A total of 150 right myopic eyes that underwent SMILE or FS-LASIK surgery were included in this retrospective study, 75 eyes in each group. The corneal hysteresis (CH) and the corneal resistance factor (CRF) with the corneal HOAs of the anterior, posterior, and total cornea were assessed preoperatively and three months postoperatively. Multivariate linear regression was applied to determine the correlations. Results. The preoperative CRF was significantly correlated with the induced 3rd–6th-order HOAs and spherical aberration of the anterior surface and the total cornea after SMILE and FS-LASIK surgeries (P < 0.05), postoperatively. The CRF was significantly correlated with the induced vertical coma of the anterior and posterior surfaces and the total cornea after SMILE surgery (P < 0.05). There was a significant correlation between the CRF and the induced posterior corneal horizontal coma after FS-LASIK surgery (P = 0.013). Conclusions. The corneal biomechanics affect the surgically induced corneal HOAs after SMILE and FS-LASIK surgery, which may be meaningful for screening the patients preoperatively and optimizing the visual qualities postoperatively. PMID:26483975

  8. In vivo photoacoustic tomography of mouse cerebral edema induced by cold injury

    NASA Astrophysics Data System (ADS)

    Xu, Zhun; Zhu, Quing; Wang, Lihong V.

    2011-06-01

    For the first time, we have implemented photoacoustic tomography (PAT) to image the water content of an edema in vivo. We produced and imaged a cold-induced cerebral edema transcranially, then obtained blood vessel and water accumulation images at 610 and 975 nm, respectively. We tracked the changes at 12, 24, and 36 h after the cold injury. The blood volume decreased after the cold injury, and the maximum area of edema was observed 24 h after the cold injury. We validated PAT of the water content of the edema through magnetic Resonance Imaging and the water spectrum from the spectrophotometric measurement.

  9. Severing corneal nerves in one eye induces sympathetic loss of immune privilege and promotes rejection of future corneal allografts placed in either eye.

    PubMed

    Paunicka, K J; Mellon, J; Robertson, D; Petroll, M; Brown, J R; Niederkorn, J Y

    2015-06-01

    Less than 10% of corneal allografts undergo rejection even though HLA matching is not performed. However, second corneal transplants experience a threefold increase in rejection, which is not due to prior sensitization to histocompatibility antigens shared by the first and second transplants since corneal grafts are selected at random without histocompatibility matching. Using a mouse model of penetrating keratoplasty, we found that 50% of the initial corneal transplants survived, yet 100% of the subsequent corneal allografts (unrelated to the first graft) placed in the opposite eye underwent rejection. The severing of corneal nerves that occurs during surgery induced substance P (SP) secretion in both eyes, which disabled T regulatory cells that are required for allograft survival. Administration of an SP antagonist restored immune privilege and promoted graft survival. Thus, corneal surgery produces a sympathetic response that permanently abolishes immune privilege of subsequent corneal allografts, even those placed in the opposite eye and expressing a completely different array of foreign histocompatibility antigens from the first corneal graft. PMID:25872977

  10. Involvement of COX2-Thromboxane Pathway in TCDD-Induced Precardiac Edema in Developing Zebrafish

    PubMed Central

    Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E.; Stegeman, John J.; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

    2015-01-01

    The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was cancelled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish. PMID:24858302

  11. Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish.

    PubMed

    Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E; Stegeman, John J; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

    2014-09-01

    The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish. PMID:24858302

  12. Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice.

    PubMed

    Guo, Chuanlong; Li, Mengshuang; Qi, Xia; Lin, Guiming; Cui, Fenghua; Li, Fengjie; Wu, Xianggen

    2016-01-01

    Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy. PMID:27405815

  13. Inhibitory effect of polysulfated heparin endostatin on alkali burn induced corneal neovascularization in rabbits

    PubMed Central

    Li, Zhao-Na; Yuan, Zhong-Fang; Mu, Guo-Ying; Hu, Ming; Cao, Li-Jun; Zhang, Ya-Li; Liu, Lei; Ge, Ming-Xu

    2015-01-01

    AIM To investigate anti-angiogenic effects of polysulfated heparin endostatin (PSH-ES) on alkali burn induced corneal neovascularization (NV) in rabbits. METHODS An alkali burn was made on rabbit corneas to induce corneal NV in the right eye of 24 rabbits. One day after burn creation, a 0.2 mL subconjunctival injection of 50 µg/mL PSH-ES, 50 µg/mL recombinant endostatin (ES), or normal saline was administered every other day for a total of 14d (7 injections). Histology and immunohistochemisty were used to examine corneas. Corneal NV growth was evaluated as microvessel quantity and corneal vascular endothelial growth factor (VEGF) expression was measured by immunohistochemical assay. RESULTS Subconjunctival injection of ES and PSH-ES resulted in significant corneal NV suppression, but PSH-ES had a more powerful anti-angiogenic effect than ES. Mean VEGF concentration in PSH-ES treated corneas was significantly lower than in ES treated and saline treated corneas. Histological examination showed that corneas treated with either PSH-ES or ES had significantly fewer microvessels than eyes treated with saline. Additionally corneas treated with PSH-ES had significantly fewer microvessels than corneas treated with ES. CONCLUSION Both PSH-ES and recombinant ES effectively inhibit corneal NV induced by alkali burn. However, PSH-ES is a more powerful anti-angiogenic agent than ES. This research has the potential to provide a new treatment option for preventing and treating corneal NV. PMID:25938033

  14. Involvement of NADPH oxidases in alkali burn-induced corneal injury

    PubMed Central

    GU, XUE-JUN; LIU, XIAN; CHEN, YING-YING; ZHAO, YAO; XU, MAN; HAN, XIAO-JIAN; LIU, QIU-PING; YI, JING-LIN; LI, JING-MING

    2016-01-01

    Chemical burns are a major cause of corneal injury. Oxidative stress, inflammatory responses and neovascularization after the chemical burn aggravate corneal damage, and lead to loss of vision. Although NADPH oxidases (Noxs) play a crucial role in the production of reactive oxygen species (ROS), the role of Noxs in chemical burn-induced corneal injury remains to be elucidated. In the present study, the transcription and expression of Noxs in corneas were examined by RT-qPCR, western blot analysis and immunofluorescence staining. It was found that alkali burns markedly upregulated the transcription and expression of Nox2 and Nox4 in human or mouse corneas. The inhibition of Noxs by diphenyleneiodonium (DPI) or apocynin (Apo) effectively attenuated alkali burn-induced ROS production and decreased 3-nitrotyrosine (3-NT) protein levels in the corneas. In addition, Noxs/CD11b double-immunofluorescence staining indicated that Nox2 and Nox4 were partially co-localized with CD11b. DPI or Apo prevented the infiltration of CD11b-positive inflammatory cells, and inhibited the transcription of inflammatory cytokines following alkali burn-induced corneal injury. In our mouse model of alkali burn-induced corneal injury, corneal neovascularization (CNV) occurred on day 3, and it affected 50% of the whole area of the cornea on day 7, and on day 14, CNV coverage of the cornea reached maximum levels. DPI or Apo effectively attenuated alkali burn-induced CNV and decreased the mRNA levels of angiogenic factors, including vascular endothelial growth factor (VEGF), VEGF receptors and matrix metalloproteinases (MMPs). Taken together, our data indicate that Noxs play a role in alkali burn-induced corneal injury by regulating oxidative stress, inflammatory responses and CNV, and we thus suggest that Noxs are a potential therapeutic target in the future treatment of chemical-induced corneal injury. PMID:27221536

  15. [Endothelial function in contact lens-induced deep corneal opacities].

    PubMed

    Göbbels, M; Wähning, A; Spitznas, M

    1989-01-01

    Deep stromal and preendothelial corneal opacities have been described to be a problem of growing importance in contact lens wearers, above all in those with a more than ten-year-old history of contact lens wearing. In the present study the corneal endothelial permeability of 21 patients with a more than ten-year-old history of contact lens (HEMA 38%) wearing has been determined and compared with that of an age-matched group of 8 healthy individuals without ocular disease. The corneal endothelial permeability has been measured by a computerized automated fluorophotometer (Coherent Radiation Fluorotron Master) after topical application of a Na-fluorescein solution according to the method described by Jones and Maurice. The corneal endothelial permeability of contact lens wearers with deep corneal opacities has been found to be significantly (p = 0.05) increased when compared with contact lens wearers without corneal opacities. Contact lens wearers without corneal opacities showed no significant increase of their endothelial permeability in comparison to the control group. PMID:2583637

  16. Sodium hydrogen exchanger as a mediator of hydrostatic edema induced intestinal contractile dysfunction

    PubMed Central

    Uray, Karen S.; Shah, Shinil K.; Radhakrishnan, Ravi S.; Jimenez, Fernando; Walker, Peter A.; Stewart, Randolph H.; Laine, Glen A.; Cox, Charles S.

    2010-01-01

    Background Resuscitation-induced intestinal edema is associated with early and profound mechanical changes in intestinal tissue. We hypothesize that the sodium hydrogen exchanger (NHE), a mechano-responsive ion channel, is a mediator of edema-induced intestinal contractile dysfunction. Methods An animal model of hydrostatic intestinal edema was utilized for all experiments. NHE isoforms 1-3 mRNA and protein were evaluated. Subsequently, the effects of NHE inhibition (with 5-(N-ethyl-N-isopropyl) amiloride (EIPA)) on wet to dry ratios, signal transduction and activator of transcription (STAT)-3, intestinal smooth muscle myosin light chain (MLC) phosphorylation, intestinal contractile activity, and intestinal transit were measured. Results NHE1-3 mRNA and protein levels were significantly increased in the small intestinal mucosa with the induction of intestinal edema. Administration of EIPA, an NHE inhibitor, attenuated validated markers of intestinal contractile dysfunction induced by edema as measured by decreased STAT-3 activation, increased MLC phosphorylation, improved intestinal contractile activity, and enhanced intestinal transit. Conclusion The mechano-responsive ion channel NHE may mediate edema-induced intestinal contractile dysfunction, possibly via a STAT-3 related mechanism. PMID:20553904

  17. Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema.

    PubMed

    Sharma, R K; Choudhary, R C; Reddy, M K; Ray, A; Ravi, K

    2015-01-01

    To investigate the role of posterior hypothalamus and central neurotransmitters in the pulmonary edema due to hypobaric hypoxia, rats were placed in a high altitude simulation chamber (barometric pressure-294.4 mmHg) for 24 h. Exposure to hypobaric hypoxia resulted in increases in mean arterial blood pressure, renal sympathetic nerve activity, right ventricular systolic pressure, lung wet to dry weight ratio and Evans blue dye leakage. There was a significant attenuation in these responses to hypobaric hypoxia (a) after lesioning posterior hypothalamus and (b) after chronic infusion of GABAA receptor agonist muscimol into posterior hypothalamus. No such attenuation was evident with the chronic infusion of the nitric oxide donor SNAP into the posterior hypothalamus. It is concluded that in hypobaric hypoxia, there is over-activity of posterior hypothalamic neurons probably due to a local decrease in GABA-ergic inhibition which increases the sympathetic drive causing pulmonary hypertension and edema. PMID:25448396

  18. The Effect of TIP on Pneumovirus-Induced Pulmonary Edema in Mice

    PubMed Central

    van den Berg, Elske; Bem, Reinout A.; Bos, Albert P.; Lutter, Rene; van Woensel, Job B. M.

    2014-01-01

    Background Pulmonary edema plays a pivotal role in the pathophysiology of respiratory syncytial virus (RSV)-induced respiratory failure. In this study we determined whether treatment with TIP (AP301), a synthetic cyclic peptide that mimics the lectin-like domain of human TNF, decreases pulmonary edema in a mouse model of severe human RSV infection. TIP is currently undergoing clinical trials as a therapy for pulmonary permeability edema and has been shown to decrease pulmonary edema in different lung injury models. Methods C57BL/6 mice were infected with pneumonia virus of mice (PVM) and received TIP or saline (control group) by intratracheal instillation on day five (early administration) or day seven (late administration) after infection. In a separate set of experiments the effect of multiple dose administration of TIP versus saline was tested. Pulmonary edema was determined by the lung wet-to-dry (W/D) weight ratio and was assessed at different time-points after the administration of TIP. Secondary outcomes included clinical scores and lung cellular response. Results TIP did not have an effect on pulmonary edema in different dose regimens at different time points during PVM infection. In addition, TIP administration did not affect clinical severity scores or lung cellular response. Conclusion In this murine model of severe RSV infection TIP did not affect pulmonary edema nor course of disease. PMID:25047452

  19. The Effects of Aquaporin-1 in Pulmonary Edema Induced by Fat Embolism Syndrome.

    PubMed

    Zhang, Yiwei; Tian, Kun; Wang, Yan; Zhang, Rong; Shang, Jiawei; Jiang, Wei; Wang, Aizhong

    2016-01-01

    This study was designed to investigate the role of aquaporin1 (AQP1) in the pathologic process of pulmonary edema induced by fat embolism syndrome (FES) and the effects of a free fatty acid (FFA) mixture on AQP1 expression in pulmonary microvascular endothelial cells (PMVECs). In vivo, edema was more serious in FES mice compared with the control group. The expression of AQP1 and the wet-to-dry lung weight ratio (W/D) in the FES group were significantly increased compared with the control group. At the same time, inhibition of AQP1 decreased the pathological damage resulting from pulmonary edema. Then we performed a study in vitro to investigate whether AQP1 was induced by FFA release in FES. The mRNA and protein level of AQP1 were increased by FFAs in a dose- and time-dependent manner in PMVECs. In addition, the up-regulation of AQP1 was blocked by the inhibitor of p38 kinase, implicating the p38 MAPK pathway as involved in the FFA-induced AQP1 up-regulation in PMVECs. Our results demonstrate that AQP1 may play important roles in pulmonary edema induced by FES and can be regarded as a new therapy target for treatment of pulmonary edema induced by FES. PMID:27455237

  20. The Effects of Aquaporin-1 in Pulmonary Edema Induced by Fat Embolism Syndrome

    PubMed Central

    Zhang, Yiwei; Tian, Kun; Wang, Yan; Zhang, Rong; Shang, Jiawei; Jiang, Wei; Wang, Aizhong

    2016-01-01

    This study was designed to investigate the role of aquaporin1 (AQP1) in the pathologic process of pulmonary edema induced by fat embolism syndrome (FES) and the effects of a free fatty acid (FFA) mixture on AQP1 expression in pulmonary microvascular endothelial cells (PMVECs). In vivo, edema was more serious in FES mice compared with the control group. The expression of AQP1 and the wet-to-dry lung weight ratio (W/D) in the FES group were significantly increased compared with the control group. At the same time, inhibition of AQP1 decreased the pathological damage resulting from pulmonary edema. Then we performed a study in vitro to investigate whether AQP1 was induced by FFA release in FES. The mRNA and protein level of AQP1 were increased by FFAs in a dose- and time-dependent manner in PMVECs. In addition, the up-regulation of AQP1 was blocked by the inhibitor of p38 kinase, implicating the p38 MAPK pathway as involved in the FFA-induced AQP1 up-regulation in PMVECs. Our results demonstrate that AQP1 may play important roles in pulmonary edema induced by FES and can be regarded as a new therapy target for treatment of pulmonary edema induced by FES. PMID:27455237

  1. Swimming-induced immersion pulmonary edema while snorkeling can be rapidly life-threatening: case reports.

    PubMed

    Cochard, G; Henckes, A; Deslandes, S; Noël-Savina, E; Bedossa, M; Gladu, G; Ozier, Y

    2013-01-01

    It is well known that immersion pulmonary edema can be life-threatening for divers using a self-contained underwater breathing apparatus (scuba). Swimming-induced pulmonary edema in otherwise healthy individuals is not an object of dispute but its real severity is not well known and is probably underestimated. We report two cases of life-threatening acute respiratory distress while swimming and snorkeling, one of which is well documented for swimming-induced pulmonary edema. The interest of these case reports lies in the suddenness of these life-threatening events. Such accidents can mimic a loss of consciousness due to cardiac dysrhythmia and lead to drowning. In the case of swimming-induced pulmonary edema, the prognosis is far better than for a cardiac disorder, but it is also dependent on the efficiency of the supervision. Swimmers, divers, race organizers and supervising physicians should be given knowledge of this pathology and its potentially acute occurrence. Adequate organizational dispositions are mandatory to prevent swimming-induced pulmonary edema-related deaths. PMID:24224285

  2. Effects of Astaxanthin from Litopenaeus Vannamei on Carrageenan-Induced Edema and Pain Behavior in Mice.

    PubMed

    Kuedo, Zulkiflee; Sangsuriyawong, Anantita; Klaypradit, Wanwimol; Tipmanee, Varomyalin; Chonpathompikunlert, Pennapa

    2016-01-01

    Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from astaxanthin treatment in mice: an inhibition of paw edema induced in hind paw, an increase in mechanical paw withdrawal threshold and thermal paw withdrawal latency, and a reduction in the amount of myeloperoxidase enzyme and lipid peroxidation products in the paw. Furthermore the effect was comparable to indomethacin, a standard treatment for inflammation symptoms. Due to adverse effects of indomethacin on cardiovascular and gastrointestinal systems, our study suggests promising prospect of astaxanthin extract as an anti-inflammatory alternative against carrageenan-induced paw edema and pain behavior. PMID:27007359

  3. Amiodarone-induced pulmonary toxicity mimicking acute pulmonary edema.

    PubMed

    Fabiani, Iacopo; Tacconi, Danilo; Grotti, Simone; Brandini, Rossella; Salvadori, Claudia; Caremani, Marcello; Bolognese, Leonardo

    2011-05-01

    Amiodarone is a highly effective antiarrhythmic drug. Its long-term use may, however, lead to several adverse effects, with pulmonary toxicity being the most serious. The article presents the case of a 78-year-old woman with a history of cardiac surgery, who after 2 years of amiodarone therapy for prophylactic treatment of atrial fibrillation developed amiodarone pneumonitis mimicking an acute pulmonary edema. The patient failed to respond to diuretic therapy and several courses of anti-infective therapy. Differential diagnosis of different causes of pulmonary infiltrates did not demonstrate any other abnormality. Lung biopsy findings were consistent with the diagnosis of amiodarone pneumonitis. Given the widespread use of amiodarone as an antiarrhythmic agent, pneumologists and cardiologists should consider this important adverse effect as a differential diagnosis of pulmonary distress refractory to therapy in all patients treated with amiodarone who present with respiratory symptoms and pneumonia-like illness. PMID:19924000

  4. Involvement of NADPH oxidases in alkali burn-induced corneal injury.

    PubMed

    Gu, Xue-Jun; Liu, Xian; Chen, Ying-Ying; Zhao, Yao; Xu, Man; Han, Xiao-Jian; Liu, Qiu-Ping; Yi, Jing-Lin; Li, Jing-Ming

    2016-07-01

    Chemical burns are a major cause of corneal injury. Oxidative stress, inflammatory responses and neovascularization after the chemical burn aggravate corneal damage, and lead to loss of vision. Although NADPH oxidases (Noxs) play a crucial role in the production of reactive oxygen species (ROS), the role of Noxs in chemical burn-induced corneal injury remains to be elucidated. In the present study, the transcription and expression of Noxs in corneas were examined by RT-qPCR, western blot analysis and immunofluorescence staining. It was found that alkali burns markedly upregulated the transcription and expression of Nox2 and Nox4 in human or mouse corneas. The inhibition of Noxs by diphenyleneiodonium (DPI) or apocynin (Apo) effectively attenuated alkali burn-induced ROS production and decreased 3-nitrotyrosine (3-NT) protein levels in the corneas. In addition, Noxs/CD11b double‑immunofluorescence staining indicated that Nox2 and Nox4 were partially co-localized with CD11b. DPI or Apo prevented the infiltration of CD11b-positive inflammatory cells, and inhibited the transcription of inflammatory cytokines following alkali burn-induced corneal injury. In our mouse model of alkali burn-induced corneal injury, corneal neovascularization (CNV) occurred on day 3, and it affected 50% of the whole area of the cornea on day 7, and on day 14, CNV coverage of the cornea reached maximum levels. DPI or Apo effectively attenuated alkali burn‑induced CNV and decreased the mRNA levels of angiogenic factors, including vascular endothelial growth factor (VEGF), VEGF receptors and matrix metalloproteinases (MMPs). Taken together, our data indicate that Noxs play a role in alkali burn-induced corneal injury by regulating oxidative stress, inflammatory responses and CNV, and we thus suggest that Noxs are a potential therapeutic target in the future treatment of chemical-induced corneal injury. PMID:27221536

  5. Hypertonic saline reduces lipopolysaccharide-induced mouse brain edema through inhibiting aquaporin 4 expression

    PubMed Central

    2012-01-01

    Introduction Three percent sodium chloride (NaCl) treatment has been shown to reduce brain edema and inhibited brain aquaporin 4 (AQP4) expression in bacterial meningitis induced by Escherichia coli. Lipopolysaccharide (LPS) is the main pathogenic component of E. coli. We aimed to explore the effect of 3% NaCl in mouse brain edema induced by LPS, as well as to elucidate the potential mechanisms of action. Methods Three percent NaCl was used to treat cerebral edema induced by LPS in mice in vivo. Brain water content, IL-1β, TNFα, immunoglobulin G (IgG), AQP4 mRNA and protein were measured in brain tissues. IL-1β, 3% NaCl and calphostin C (a specific inhibitor of protein kinase C) were used to treat the primary astrocytes in vitro. AQP4 mRNA and protein were measured in astrocytes. Differences in various groups were determined by one-way analysis of variance. Results Three percent NaCl attenuated the increase of brain water content, IL-1β, TNFα, IgG, AQP4 mRNA and protein in brain tissues induced by LPS. Three percent NaCl inhibited the increase of AQP4 mRNA and protein in astrocytes induced by IL-1β in vitro. Calphostin C blocked the decrease of AQP4 mRNA and protein in astrocytes induced by 3% NaCl in vitro. Conclusions Osmotherapy with 3% NaCl ameliorated LPS-induced cerebral edema in vivo. In addition to its osmotic force, 3% NaCl exerted anti-edema effects possibly through down-regulating the expression of proinflammatory cytokines (IL-1β and TNFα) and inhibiting the expression of AQP4 induced by proinflammatory cytokines. Three percent NaCl attenuated the expression of AQP4 through activation of protein kinase C in astrocytes. PMID:23036239

  6. Ability of eugenol to reduce tongue edema induced by Dieffenbachia picta Schott in mice.

    PubMed

    Dip, Etyene Castro; Pereira, Nuno Alvarez; Fernandes, Patricia Dias

    2004-05-01

    Dieffenbachia picta Schott (Araceae), known in Brazil as "comigo-ninguém-pode" is an ornamental plant with toxic properties. Its juice, when chewed, causes a painful edema of the oral mucous membranes, buccal ulcerations and tongue hypertrophy. This acute inflammation sometimes becomes severe enough to produce glottis obstruction, respiratory compromise and death. Eugenol (4-alil-2-metoxiphenol), the essential oil extracted from Caryophyllus aromaticus (Myrtaceae) is widely used in odontology. In this study, our objective was to standardize, in mice, a measurable methodology for the tongue edema induced by the topical application of the D. picta stem juice; evaluate the effects of eugenol in this model and compare the results with emergency treatment used in hospitals. Our results show that in spite of a small increase in edema a few minutes after administration, emergency treatment reduced by 70% the overall edema. When compared with the combination of the above drugs, eugenol, even at the smallest dose of 5 microg/kg, regardless of the chosen administration route, or the moment the treatment began, presents better results in the reduction and inhibition of the tongue edema induced by the D. picta juice. PMID:15109894

  7. TCDD Induced Pericardial Edema and Relative COX-2 Expression in Medaka (Oryzias Latipes) Embryos

    PubMed Central

    Dong, Wu; Matsumura, Fumio; Kullman, Seth W.

    2010-01-01

    Exposure to dioxin and other aryl hydrocarbon receptor (AhR) ligands results in multiple, specific developmental cardiovascular phenotypes including pericardial edema and circulatory failure in small aquarium fish models. Although phenotypes are well described, mechanistic underpinnings for such toxicities remain elusive. Here we suggest that AhR activation results in stimulation of inflammation and “eicosanoid” pathways, which contribute to the observed developmental, cardiovascular phenotypes. We demonstrate that medaka embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.05–1 ppb) during early development result in a dose-related increase in the prevalence of pericardial edema and that this phenotype correlates with an increase in cyclooxygenase-2 (COX-2) gene expression. Those individuals exhibiting the edema phenotype had significantly greater COX-2 mRNA than their nonedematous cohort. Selective pharmacological inhibition of COX-2, with NS-398, and genetic knock down of COX-2 with a translation initiation morpholino significantly attenuated prevalence and severity of edema phenotype. Subsequently, exposures of medaka embryos to arachidonic acid (AA) resulted in recapitulation of the pericardial edema phenotype and significantly increased COX-2 expression only in those individuals exhibiting the edema phenotype compared with their nonedematous cohort. AA exposure does not result in significant induction of cytochrome P450 1A expression, suggesting that pericardial edema can be induced independent of AhR/aryl hydrocarbon receptor nuclear translocator/dioxin response element interactions. Results from this study demonstrate that developmental exposure to TCDD results in an induction of inflammatory mediators including COX-2, which contribute to the onset, and progression of heart dysmorphogenesis in the medaka model. PMID:20801906

  8. Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention.

    PubMed

    Horita, Shoko; Nakamura, Motonobu; Satoh, Nobuhiko; Suzuki, Masashi; Seki, George

    2015-01-01

    Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema. PMID:26074951

  9. [Transplantation of corneal endothelial cells].

    PubMed

    Amano, Shiro

    2002-12-01

    endothelial cells. Cultured rabbit corneal endothelial cells that endocytosed iron were injected into the anterior chamber of rabbits whose corneal endothelium was cryo-injured, and were pulled to Descemet's membrane by putting a magnet on the eyelid. In these rabbits, corneal edema decreased more quickly than in the control group and no intraocular pressure rise was observed during 8 weeks after the operation, suggesting that the direct delivery of cultured HCECs into the anterior chamber can be an alternative method of choice. The following obstacles should be addressed to make the transplantation of cultured corneal endothelial cells clinically applicable. 1. To reconstruct a cornea that is the same as or superior to the normal cornea, more innovation is necessary in the method of culturing and seeding HCECs. We should consider utilizing HCECs obtained from fetuses after clearing ethical issues. Moreover, we need to develop a method to enhance the cell density and the cell functions. 2. Porcine corneal stroma is promising as a carrier of HCECs instead of human corneal stroma, which is in very limited supply. The usefulness of porcine corneal stroma acellularized to prevent retrovirus infection should be evaluated. 3. To make the self immature cells applicable to corneal transplantation, we should elucidate the corneal endothelial cell specific markers and the factors that are necessary to induce self immature cells to become corneal endothelial cells. 4. The direct delivery of cultured HCECs into the anterior chamber can be an alternative method of choice when its long-term safety is confirmed. PMID:12610838

  10. TGF-{beta}2 inhibits AKT activation and FGF-2-induced corneal endothelial cell proliferation

    SciTech Connect

    Lu Jiawei; Lu Zhenyu; Reinach, Peter

    2006-11-01

    The corneal endothelial cells form a boundary layer between anterior chamber and cornea. This single cell layer is important to maintain cornea transparency by eliciting net fluid transport into the anterior chamber. Injuries of the corneal endothelial layer in humans lead to corneal swelling and translucence. This hindrance is thought to be due to limited proliferative capacity of the endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 2 (TGF-{beta}2) are both found in aqueous humor, and these two cytokines promote and inhibit cell growth, respectively. The intracellular signaling mechanisms by which TGF-{beta}2 suppresses the mitogenic response to FGF-2, however, remain unclear. We have addressed this question by investigating potential crosstalk between FGF-2-induced and TGF-{beta}2-regulated intracellular signaling events in cultured bovine corneal endothelial (BCE) cells. We found that TGF-{beta}2 and FGF-2 oppositely affect BCE cell proliferation and TGF-{beta}2 can override the stimulating effects of FGF-2 by increasing COX-2 expression in these cells. Consistent with these findings, overexpression of COX-2 significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific inhibitor NS398 reversed the effect of TGF-{beta}2 on FGF-2-induced cell proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the AKT pathway, TGF-{beta}2 and PGE-2 both inhibit this pathway. In accordance with the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These findings suggest that the mitogenic response to FGF-2 in vivo in the corneal endothelial layer may be inhibited by TGF-{beta}2-induced suppression of the PI3-kinase/AKT signaling pathway.

  11. Pharmacological investigation of the nociceptive response and edema induced by venom of the scorpion Tityus serrulatus.

    PubMed

    Nascimento, Elias B; Costa, Karina A; Bertollo, Caryne M; Oliveira, Antônio Carlos P; Rocha, Leonardo T S; Souza, Adriano L S; Glória, Maria Beatriz A; Moraes-Santos, Tasso; Coelho, Márcio M

    2005-04-01

    In this study we characterized the nociceptive response and edema induced by the venom of the scorpion Tityus serrulatus in rats and mice and carried out a preliminary pharmacological investigation of the mechanisms involved in these responses. Intraplantar injection of the venom (1 or 10mug) induced edema and a marked ipsilateral nociceptive response, characterized by thermal and mechanical allodynia and paw licking behaviour. The nociceptive response was inhibited by previous intraperitoneal administration of indomethacin (4mg/kg), dipyrone (200mg/kg), cyproheptadine (10mg/kg) or morphine (5 or 10mg/kg), but not by dexamethasone (1 or 4mg/kg) or promethazine (1 or 5mg/kg). The edema was inhibited by previous treatment with promethazine (5 or 10mg/kg) or cyproheptadine (5 or 10mg/kg), but not by indomethacin (2 or 4mg/kg), dexamethasone (1 or 4mg/kg) or cromolyn (40 or 80mg/kg). Some bioactive amines, including histamine and 5-hydroxytryptamine, were found in the venom in low concentrations. In conclusion, the nociceptive response and edema induced by the venom of T. serrulatus may result from the action of multiple mediators including eicosanoids, histamine and 5-hydroxytryptamine. These results may lead to a better understanding of the host response to potent animal toxins and also give insights into a more rational pharmacological approach to alleviate the intense pain associated with the scorpion envenomation. PMID:15777954

  12. Effect of Liraglutide on Corneal Kindling Epilepsy Induced Depression and Cognitive Impairment in Mice.

    PubMed

    Koshal, Prashant; Kumar, Puneet

    2016-07-01

    GLP-1 play important role in neuroprotection and GLP-1 receptor deficit mice showed decreased seizure threshold and increased cognitive impairment. Therefore, study was premeditated to investigate the effect of liraglutide (GLP-1 analogue) on cornel kindling epilepsy induced co-morbidities in mice. Corneal kindling was induced by electrical stimulation (6 mA, 50 Hz, 3 s); twice daily for 13 days. Liraglutide (75 and 150 µg/kg) and phenytoin (20 mg/kg) were administered in corneal kindled groups. On day 14, elevated plus maze, passive shock avoidance paradigms were performed, and on day 15, retention was taken. On day 16 tail suspension test were performed. On 20th day challenge test was performed with same electrical stimulation and retention was observed on elevated plus maze and passive avoidance paradigm. Animal were sacrificed on 21st day for biochemical (LPO, GSH, and nitrite) and neurochemical (GABA, glutamate, DA, NE, 5-HT and their metabolites) estimation. Electrical stimulation by corneal electrode for 13 days developed generalized clonic seizures, increased cognitive impairment, oxidative stress and neurochemical alteration in mice brain. Co-treatment with liraglutide (75 and 150 μg/kg) significantly prevented the seizure severity, restored behavioural activity, oxidative stress and restored the altered level of neurotransmitters observed in corneal kindled mouse. PMID:27017512

  13. Proangiogenic role of ephrinB1/EphB1 in basic fibroblast growth factor-induced corneal angiogenesis.

    PubMed

    Kojima, Takashi; Chang, Jin-Hong; Azar, Dimitri T

    2007-02-01

    Corneal neovascularization is a vision-threatening condition caused by various ocular pathological conditions. The aim of this study was to evaluate the function of the ephrin ligands and Eph receptors in vitro and in vivo in corneal angiogenesis in a mouse model. The Eph tyrosine kinase receptors and their ligands, ephrins, are expressed on the cell surface. The functions of Eph and ephrins have been shown to regulate axonal guidance, segmentation, cell migration, and angiogenesis. Understanding the roles of Eph and ephrin in corneal angiogenesis may provide a therapeutic intervention for the treatment of angiogenesis-related disorders. Immunohistochemical studies demonstrated that ephrinB1 and EphB1 were expressed in basic fibroblast growth factor (bFGF)-induced vascularized corneas. EphB1 was specifically colocalized with vascular endothelial marker CD31 surrounded by type IV collagen. EphrinB1 was expressed in corneal-resident keratocytes and neutrophils. Recombinant ephrinB1-Fc, which induces EphB receptor activation, enhanced bFGF-induced tube formation in an in vitro aortic ring assay and promoted bFGF-induced corneal angiogenesis in vivo in a corneal pocket assay. Synergistically enhanced and sustained activation of extracellular signal-regulated kinase was noted in vascular endothelial cell lines after stimulation with ephrin B1 and bFGF combinations. These results suggest that ephrinB1 plays a synergistic role in corneal neovascularization. PMID:17255342

  14. Diospyros kaki Extract Inhibits Alkali Burn-Induced Corneal Neovascularization.

    PubMed

    Yang, Sung Jae; Jo, Hyoung; Kim, Kyung-A; Ahn, Hong Ryul; Kang, Suk Woo; Jung, Sang Hoon

    2016-01-01

    The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats. PMID:26348484

  15. Anti-inflammatory effects of linezolid on carrageenan-induced paw edema in rats.

    PubMed

    Matsumoto, Kazuaki; Obara, Shigeaki; Kuroda, Yuko; Kizu, Junko

    2015-12-01

    The immunomodulatory activity of linezolid has recently been reported using in vitro experimental models. However, the anti-inflammatory activity of linezolid has not yet been demonstrated using in vivo experimental models. Therefore, the aim of the present study was to demonstrate the anti-inflammatory activity of linezolid and other anti-MRSA agents using the carrageenan-induced rat paw edema model. The pretreatment with 50 mg/kg linezolid significantly suppressed edema rates, compared with control (5% glucose), with edema rates at 0.5 and 3 h after the administration of carrageenan being 17.3 ± 3.5 and 30.8 ± 3.0%, respectively. On the other hand, edema rates were not suppressed by the pretreatments with 50 mg/kg vancomycin, teicoplanin, arbekacin, and daptomycin. Furthermore, we demonstrated that linezolid exhibited anti-inflammatory activity in a concentration-dependent manner. These effects were observed at linezolid concentrations that are achievable in human serum with conventional dosing. In conclusion, the results of the present study suggest that the anti-inflammatory activities of linezolid, in addition to its antimicrobial effects, have a protective effect against destructive inflammatory responses in areas of inflammation. PMID:26362409

  16. Inhibitory effects of PPARγ ligands on TGF-β1-induced corneal myofibroblast transformation.

    PubMed

    Jeon, Kye-Im; Kulkarni, Ajit; Woeller, Collynn F; Phipps, Richard P; Sime, Patricia J; Hindman, Holly B; Huxlin, Krystel R

    2014-05-01

    Corneal scarring, whether caused by trauma, laser refractive surgery, or infection, remains a significant problem for humans. Certain ligands for peroxisome proliferator-activated receptor gamma (PPARγ) have shown promise as antiscarring agents in a variety of body tissues. In the cornea, their relative effectiveness and mechanisms of action are still poorly understood. Here, we contrasted the antifibrotic effects of three different PPARγ ligands (15-deoxy-Δ12,14-prostaglandin J2, troglitazone, and rosiglitazone) in cat corneal fibroblasts. Western blot analyses revealed that all three compounds reduced transforming growth factor (TGF)-β1-driven myofibroblast differentiation and up-regulation of α-smooth muscle actin, type I collagen, and fibronectin expression. Because these effects were independent of PPARγ, we ascertained whether they occurred by altering phosphorylation of Smads 2/3, p38 mitogen-activated protein kinase, stress-activated protein kinase, protein kinase B, extracellular signal-regulated kinase, and/or myosin light chain 2. Only p38 mitogen-activated protein kinase phosphorylation was significantly inhibited by all three PPARγ ligands. Finally, we tested the antifibrotic potential of troglitazone in a cat model of photorefractive keratectomy-induced corneal injury. Topical application of troglitazone significantly reduced α-smooth muscle actin expression and haze in the stromal ablation zone. Thus, the PPARγ ligands tested here showed great promise as antifibrotics, both in vitro and in vivo. Our results also provided new evidence for the signaling pathways that may underlie these antifibrotic actions in corneal fibroblasts. PMID:24650561

  17. Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema

    PubMed Central

    Lucas, Rudolf; Sridhar, Supriya; Rick, Ferenc G.; Gorshkov, Boris; Umapathy, Nagavedi S.; Yang, Guang; Oseghale, Aluya; Verin, Alexander D.; Chakraborty, Trinad; Matthay, Michael A.; Zemskov, Evgeny A.; White, Richard; Block, Norman L.; Schally, Andrew V.

    2012-01-01

    Aggressive treatment with antibiotics in patients infected with Streptococcus pneumoniae induces release of the bacterial virulence factor pneumolysin (PLY). Days after lungs are sterile, this pore-forming toxin can still induce pulmonary permeability edema in patients, characterized by alveolar/capillary barrier dysfunction and impaired alveolar liquid clearance (ALC). ALC is mainly regulated through Na+ transport by the apically expressed epithelial sodium channel (ENaC) and the basolaterally expressed Na+/K+-ATPase in type II alveolar epithelial cells. Because no standard treatment is currently available to treat permeability edema, the search for novel therapeutic candidates is of high priority. We detected mRNA expression for the active receptor splice variant SV1 of the hypothalamic polypeptide growth hormone-releasing hormone (GHRH), as well as for GHRH itself, in human lung microvascular endothelial cells (HL-MVEC). Therefore, we have evaluated the effect of the GHRH agonist JI-34 on PLY-induced barrier and ALC dysfunction. JI-34 blunts PLY-mediated endothelial hyperpermeability in monolayers of HL-MVEC, in a cAMP-dependent manner, by means of reducing the phosphorylation of myosin light chain and vascular endothelial (VE)-cadherin. In human airway epithelial H441 cells, PLY significantly impairs Na+ uptake, but JI-34 restores it to basal levels by means of increasing cAMP levels. Intratracheal instillation of PLY into C57BL6 mice causes pulmonary alveolar epithelial and endothelial hyperpermeability as well as edema formation, all of which are blunted by JI-34. These findings point toward a protective role of the GHRH signaling pathway in PLY-induced permeability edema. PMID:22308467

  18. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

    SciTech Connect

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W.

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

  19. On the need to compensate edema-induced dose reductions in pre-planned 131Cs prostate brachytherapy

    PubMed Central

    Chen, Z. Jay; Deng, Jun; Roberts, Kenneth; Nath, Ravinder

    2008-01-01

    Purpose Surgical-trauma-induced edema and its protracted resolution can lead to significant dose reduction in pre-planned 131Cs prostate brachytherapy. The purpose of this work was to examine whether these dose reductions should be actively compensated and to estimate the magnitude of additional irradiations needed for dose compensation. Methods and Materials Quantitative edema resolution characteristics observed by Waterman et. el. were used to examine the physical and radiobiological effects of prostate edema in pre-planned 131Cs implants. The need for dose compensation was assessed based on the dose-responses observed in 125I and 103Pd prostate implants. Biologically effective dose calculated with full consideration of edema evolution was used to estimate the additional irradiations needed for dose compensation. Results Edema-induced dose reduction in pre-planned 131Cs implants could easily exceed 10% prescription dose for implants with moderate or large edemas. These dose reductions could lead to more than 10% reduction in biochemical recurrence-free survival for individual patients if the effect of edema was ignored. For a prescribed dose of 120 Gy, the number of 2-Gy external-beam fractions needed to compensate a 5%, 10%, 15%, 20%, or 25% edema-induced dose reduction could be 1, 4, 6, 7, or 9, respectively, for prostate cancers with a median potential doubling time of 42 days. The required additional irradiation increases for tumors that are fast growing and/or are less efficient in sub-lethal damage repair. Conclusions Compensation of edema-induced dose reductions in pre-planned 131Cs prostate brachytherapy should be actively considered for those implants with moderate or large edemas. PMID:17980500

  20. On the Need to Compensate for Edema-Induced Dose Reductions in Preplanned {sup 131}Cs Prostate Brachytherapy

    SciTech Connect

    Chen, Z. Jay Deng Jun; Roberts, Kenneth; Nath, Ravinder

    2008-01-01

    Purpose: Surgical trauma-induced edema and its protracted resolution can lead to significant dose reductions in preplanned {sup 131}Cs prostate brachytherapy. The purpose of this work was to examine whether these dose reductions should be actively compensated for and to estimate the magnitude of the additional irradiation needed for dose compensation. Methods and Materials: The quantitative edema resolution characteristics observed by Waterman et al. were used to examine the physical and radiobiologic effects of prostate edema in preplanned {sup 131}Cs implants. The need for dose compensation was assessed using the dose responses observed in {sup 125}I and {sup 103}Pd prostate implants. The biologically effective dose, calculated with full consideration of edema evolution, was used to estimate the additional irradiation needed for dose compensation. Results: We found that the edema-induced dose reduction in preplanned {sup 131}Cs implants could easily exceed 10% of the prescription dose for implants with moderate or large edema. These dose reductions could lead to a >10% reduction in the biochemical recurrence-free survival for individual patients if the effect of edema was ignored. For a prescribed dose of 120 Gy, the number of 2-Gy external beam fractions needed to compensate for a 5%, 10%, 15%, 20%, and 25% edema-induced dose reduction would be one, four, six, seven, and nine, respectively, for prostate cancer with a median potential doubling time of 42 days. The required additional irradiation increased for fast-growing tumors and/or those less efficient in sublethal damage repair. Conclusion: Compensation of edema-induced dose reductions in preplanned {sup 131}Cs prostate brachytherapy should be actively considered for those implants with moderate or large edema.

  1. Effect of transcutaneous electrical stimulation on nociception and edema induced by peripheral serotonin.

    PubMed

    Santos, Cristiane M F; Francischi, Janetti N; Lima-Paiva, Patrícia; Sluka, Kathleen A; Resende, Marcos A

    2013-07-01

    Transcutaneous electrical nerve stimulation (TENS) is defined as the application of an electrical current to the skin through surface electrodes for pain relief. Various theories have been proposed in order to explain the analgesic mechanism of TENS. Recent studies have demonstrated that part of this analgesia is mediated through neurotransmitters acting at peripheral sites. The aim of this study was to investigate the effects of low frequency (LF: 10 HZ) TENS and high frequency (HF: 130 HZ) TENS on hyperalgesia and edema when applied before the serotonin (5-HT) administered into the rat paw. LF and HF TENS were applied to the right paw for 20 min, and 5-HT was administered immediately after TENS. The Hargreaves method was used to measure nociception, while the hydroplethysmometer (Ugo Basile®) was used to measure edema. Neither HF nor LF TENS inhibited 5-HT-induced edema. However, LF TENS, but not HF TENS, completely reduced 5-HT-induced hyperalgesia. Pre-treatment of the paw with naltrexone, prior to application of TENS, (Nx: 50 μg; I.pl.) showed a complete blockade of the analgesic effect induced by low frequency TENS. Thus, our results confirmed the lack of an anti-inflammatory effect through the use of TENS as well as the participation of peripheral endogenous opioid receptors in LF TENS analgesia in addition to its central action. PMID:23336713

  2. Inhibitory effects of 90Sr/90Y β-irradiation on alkali burn-induced corneal neovascularization in rats

    PubMed Central

    LIN, YUANQIANG; MA, QINGJIE; LIN, SHAN; ZHOU, HONGYAN; WEN, QIANG; GAO, SHI; CHENG, GUANGHUI

    2016-01-01

    The aim of the present study was to investigate the inhibitory effects of 90Sr-90Y β-irradiation in a rat model of alkali burn-induced corneal neovascularization (CNV). Alkali burn-induced CNV was induced in the right eyes of 30 female Wistar rats, which were randomly divided into the following three groups (n=10/group): i) The alkali burn control group, which received a balanced salt solution treatment; ii) group 1, which received treatment with angiogenesis inhibitors; and iii) group 2, which received 90Sr-90Y β-irradiation treatment. A further 10 female Wistar rats comprised a blank control group and received only balanced salt solution. Digital photographs of the corneas were acquired and the area of NV was calculated. In addition, the expression levels of matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1 and VEGFR-2 in alkali-burned rat corneas were determined using western blot analysis. The results suggested that the number of new vessels and the area of CNV were significantly decreased in groups 1 and 2, as compared with the alkali burn group at each time point (P<0.05). In addition, the number of inflammatory cells and the degree of edema were decreased in groups 1 and 2, as compared with the alkali burn group, with group 2 exhibiting the most marked reduction. Western blot analysis demonstrated that the expression levels of MMP-9, VEGF, VEGFR-1 and VEGFR-2 were significantly decreased in groups 1 and 2, as compared with the alkali burn control group, with group 2 exhibiting the most significant reduction (P<0.05). The results of the present study suggested that 90Sr-90Y β-irradiation and angiogenesis inhibitor treatments were able to inhibit alkali burn-induced CNV, although 90Sr-90Y β-irradiation may be more effective. PMID:26893623

  3. Spontaneous Corneal Hydrops in a Patient with a Corneal Ulcer

    PubMed Central

    Batawi, Hatim; Kothari, Nikisha; Camp, Andrew; Bernhard, Luis; Karp, Carol L.; Galor, Anat

    2016-01-01

    Purpose We report the case of a 77-year-old man with no history of keratoconus or other ectatic disorders who presented with corneal hydrops in the setting of a corneal ulcer. The risk factors, pathogenesis and treatment options of corneal hydrops are discussed. Method This is an observational case report study. Results A 77-year-old man presented with a 1-day history of severe pain, redness, mucous discharge and photophobia in the right eye. A slit-lamp examination of the right eye showed an area of focal corneal edema and protrusion. Within the area of edema and protrusion, there was an infiltrate with an overlying epithelial defect consistent with an infectious corneal ulcer. The Seidel test showed no leakage, so a clinical diagnosis of corneal hydrops associated with nonperforated corneal ulcer was made. With appropriate antibiotic treatment, the corneal ulcer and hydrops both resolved over a 1-month period. Conclusion Corneal hydrops can occur in the setting of corneal infections. PMID:26889160

  4. Lacritin Salvages Human Corneal Epithelial Cells from Lipopolysaccharide Induced Cell Death

    PubMed Central

    Vantaku, Venkat Rao; Gupta, Geetika; Rapalli, Krishna Chaitanya; Karnati, Roy

    2015-01-01

    Innate immunity of the corneal epithelium is conferred by proteinaceous secretions from the epithelium and associated lacrimal and meibomian glands. Lacritin, an eye-specific protein with anti-microbial, cytoprotective and wound-healing properties, predominantly secreted by lacrimal glands, is absent in conditions such as Dry eye and Keratitis. In view of the biological significance of lacritin in human eye, we investigated its role in human corneal epithelial (HCE) cells during lipopolysaccharide (LPS)-induced infection. LPS-challenged HCE cells demonstrated apoptosis-mediated cell death and elevated lacritin levels. The LPS-induced cell death is alleviated with exogenous supplementation of recombinant lacritin. This cytoprotective effect of lacritin is mediated through Cyclooxygenase-2 (COX-2). This study is the first to highlight the protective role of lacritin and mechanism of its action during bacterial infection of cornea in vitro. PMID:26670139

  5. Lacritin Salvages Human Corneal Epithelial Cells from Lipopolysaccharide Induced Cell Death.

    PubMed

    Vantaku, Venkat Rao; Gupta, Geetika; Rapalli, Krishna Chaitanya; Karnati, Roy

    2015-01-01

    Innate immunity of the corneal epithelium is conferred by proteinaceous secretions from the epithelium and associated lacrimal and meibomian glands. Lacritin, an eye-specific protein with anti-microbial, cytoprotective and wound-healing properties, predominantly secreted by lacrimal glands, is absent in conditions such as Dry eye and Keratitis. In view of the biological significance of lacritin in human eye, we investigated its role in human corneal epithelial (HCE) cells during lipopolysaccharide (LPS)-induced infection. LPS-challenged HCE cells demonstrated apoptosis-mediated cell death and elevated lacritin levels. The LPS-induced cell death is alleviated with exogenous supplementation of recombinant lacritin. This cytoprotective effect of lacritin is mediated through Cyclooxygenase-2 (COX-2). This study is the first to highlight the protective role of lacritin and mechanism of its action during bacterial infection of cornea in vitro. PMID:26670139

  6. Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery.

    PubMed

    Igarashi, Tsutomu; Ohsawa, Ikuroh; Kobayashi, Maika; Igarashi, Toru; Suzuki, Hisaharu; Iketani, Masumi; Takahashi, Hiroshi

    2016-01-01

    In phacoemulsification, ultrasound induces hydroxyl radical (·OH) formation, damaging corneal endothelium. Whether H2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H2 was dissolved in a commercial irrigating solution. The effects of H2 against ·OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H2-dissolved solution. The effects of H2 in phacoemulsification were evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2 group. In conclusion, H2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage. PMID:27498755

  7. Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery

    PubMed Central

    Igarashi, Tsutomu; Ohsawa, Ikuroh; Kobayashi, Maika; Igarashi, Toru; Suzuki, Hisaharu; Iketani, Masumi; Takahashi, Hiroshi

    2016-01-01

    In phacoemulsification, ultrasound induces hydroxyl radical (·OH) formation, damaging corneal endothelium. Whether H2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H2 was dissolved in a commercial irrigating solution. The effects of H2 against ·OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H2-dissolved solution. The effects of H2 in phacoemulsification were evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2 group. In conclusion, H2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage. PMID:27498755

  8. Hypoxic preconditioning with cobalt ameliorates hypobaric hypoxia induced pulmonary edema in rat.

    PubMed

    Shukla, Dhananjay; Saxena, Saurabh; Purushothaman, Jayamurthy; Shrivastava, Kalpana; Singh, Mrinalini; Shukla, Shirish; Malhotra, Vineet Kumar; Mustoori, Sairam; Bansal, Anju

    2011-04-10

    Exposure to high altitude results in hypobaric hypoxia which is considered as an acute physiological stress and often leads to high altitude maladies such as high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The best way to prevent high altitude injuries is hypoxic preconditioning which has potential clinical usefulness and can be mimicked by cobalt chloride. Preconditioning with cobalt has been reported to provide protection in various tissues against ischemic injury. However, the effect of preconditioning with cobalt against high altitude induced pulmonary edema has not been investigated in vivo. Therefore, in the present study, rats pretreated with saline or cobalt (12.5mg/kg body weight) for 7days were exposed to hypobaric hypoxia of 9142m for 5h at 24°C. Formation of pulmonary edema was assessed by measuring transvascular leakage of sodium fluorescein dye and lung water content. Total protein content, albumin content, vascular endothelial growth factor (VEGF) and cytokine levels were measured in bronchoalveolar lavage fluid. Expression of HO-1, MT, NF-κB DNA binding activity and lung tissue pathology were evaluated to determine the effect of preconditioning on HAPE. Hypobaric hypoxia induced increase in transvascular leakage of sodium fluorescein dye, lung water content, lavage total protein, albumin, VEGF levels, pro-inflammatory cytokine levels, tissue expression of cell adhesion molecules and NF-κB DNA binding activity were reduced significantly after hypoxic preconditioning with cobalt. Expression of anti-inflammatory protein HO-1, MT, TGF-β and IL-6 were increased after hypoxic preconditioning. These data suggest that hypoxic preconditioning with cobalt has protective effect against HAPE. PMID:21296072

  9. Effect of Fluvoxamine on Carrageenan-Induced Paw Edema in Rats Evaluation of the Action Sites

    PubMed Central

    Hajhashemi, Valiollah; Sadeghi, Hossein; Minaiyan, Mohsen; Movahedian, Ahmad; Talebi, Ardeshir

    2011-01-01

    The present study was designed to explore the anti-inflammatory effect of fluvoxamine, as a selective serotonin reuptake inhibitor (SSRI) anti-depressant, on carrageenan-induced paw edema in more details. At first, fluvoxamine was administered intra-peritoneally (2.5, 12.5, 25 and 50 mg Kg-1) 30 min before the subplantar injection of carrageenan. Fluvoxamine was also injected intra-peritoneally at a dose of 50 mg Kg-1 30 or 90 min after carrageenan injection. Then, fluvoxamine was given intra-cerebroventricularly (25, 50 and 100 μg/rat) and intra-thecally (25, 50 and 100 μg/rat) 30 min before the carrageenan challenge. Finally, the effect of mifepristone (5 mg Kg-1), an antagonist of the glucocorticoid receptor, on the anti-edema effect of fluvoxamine (50 mg Kg-1) was investigated. Results showed that intra-peritoneal (IP) administration of fluvoxamine before or after carrageenan injection considerably inhibited paw edema response at 4 h post-carrageenan (p < 0.001), but intra-cerebroventricular (i.c.v.) and intra-thecal (i.t.) injection of fluvoxamine did not alter the degree of paw swelling. The inhibitory effect of fluvoxamine was reduced by the pretreatment of mifepristone (p < 0.01). Our results suggest that IP administration of fluvoxamine produces a noticeable anti-inflammatory effect in the carrageenan-induced paw edema in rats and at least, a part of this effect is mediated through glucocorticoid receptor. Moreover, it seems unlikely that central sites have an important role in this inhibitory effect of fluvoxamine. PMID:24250395

  10. Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells.

    PubMed

    Blazejewska, Ewa Anna; Schlötzer-Schrehardt, Ursula; Zenkel, Matthias; Bachmann, Björn; Chankiewitz, Erik; Jacobi, Christina; Kruse, Friedrich E

    2009-03-01

    The aim of this study was to investigate the transdifferentiation potential of murine vibrissa hair follicle (HF) stem cells into corneal epithelial-like cells through modulation by corneal- or limbus-specific microenvironmental factors. Adult epithelial stem cells were isolated from the HF bulge region by mechanical dissection or fluorescence-activated cell sorting using antibodies to alpha6 integrin, enriched by clonal expansion, and subcultivated on various extracellular matrices (type IV collagen, laminin-1, laminin-5, fibronectin) and in different conditioned media derived from central and peripheral corneal fibroblasts, limbal stromal fibroblasts, and 3T3 fibroblasts. Cellular phenotype and differentiation were evaluated by light and electron microscopy, real-time reverse transcription-polymerase chain reaction, immunocytochemistry, and Western blotting, using antibodies against putative stem cell markers (K15, alpha6 integrin) and differentiation markers characteristic for corneal epithelium (K12, Pax6) or epidermis (K10). Using laminin-5, a major component of the corneo-limbal basement membrane zone, and conditioned medium from limbal stromal fibroblasts, clonally enriched HF stem and progenitor cells adhered rapidly and formed regularly arranged stratified cell sheets. Conditioned medium derived from limbal fibroblasts markedly upregulated expression of cornea-specific K12 and Pax6 on the mRNA and protein level, whereas expression of the epidermal keratinocyte marker K10 was strongly downregulated. These findings suggest that adult HF epithelial stem cells are capable of differentiating into corneal epithelial-like cells in vitro when exposed to a limbus-specific microenvironment. Therefore, the HF may be an easily accessible alternative therapeutic source of autologous adult stem cells for replacement of the corneal epithelium and restoration of visual function in patients with ocular surface disorders. PMID:19074417

  11. b-FGF Induces Corneal Blood and Lymphatic Growth in a Spatially Distinct Pattern

    PubMed Central

    Hajrasouliha, Amir R.; Sadrai, Zahra; Chauhan, Sunil K.; Dana, Reza

    2013-01-01

    Purpose To study the spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by b-FGF. Methods b-FGF micropellets (80ng) were implanted in the temporal side of the cornea of Balbc/c mice. On days 1, 3, and 7 blood (heme) and lymph-angiogenesis were observed by immunofluorescence staining of corneal flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels, respectively. A second group of corneas were harvested for quantitative RT-PCR. Each cornea was divided in two different area defines as (i) pre-pellet area and (ii) opposite-pellet area. Expression of VEGF ligands were evaluated using Real-time PCR in each respective zone. Results Blood vessels grew into the cornea from the pre-pellet area while corneal lymphatic vessels grew from the opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in the pre-pellet while VEGF-D expression was mostly observed in the opposite-pellet area. VEGF-C level increased simultaneously in both areas. Conclusion A single inducing factor, i.e., b-FGF, may simultaneously provoke heme-and lymph-angiogenesis in different locations of the cornea through differential expression of VEGF ligands. This distinctive spatial pattern should be considered while evaluating the corneal predilection for inflammation beyond that which is directly visible by slit lamp examination. PMID:22467003

  12. Methotrimeprazine-induced corneal deposits and cataract revealed by urine drug profiling test.

    PubMed

    Kim, Seong Taeck; Koh, Jae Woong; Kim, Joon Mo; Kim, Won Young; Choi, Gwang Ju

    2010-11-01

    Two schizophrenic patients who had been taking medication for a long period presented with visual disturbance of 6-month duration. Slit-lamp examination revealed fine, discrete, and brownish deposits on the posterior cornea. In addition, bilateral star-shaped anterior subcapsular lens opacities, which were dense, dust-like granular deposits, were noted. Although we strongly suspected that the patient might have taken one of the drugs of the phenothiazine family, we were unable to obtain a history of medications other than haloperidol and risperidone, which were taken for 3 yr. We performed a drug profiling test using urine samples and detected methotrimeprazine. The patient underwent surgery for anterior subcapsular lens opacities. Visual acuity improved in both eyes, but the corneal deposits remained. We report an unusual case of methotrimeprazine-induced corneal deposits and cataract in a patient with psychosis, identified by using the urine drug profiling test. PMID:21060765

  13. Influence of local inhomogeneities induced in corneal ablation on the evolution of contrast sensitivity

    NASA Astrophysics Data System (ADS)

    Ortiz, Dolores; Saiz, Jose M.; González, Francisco

    2004-04-01

    The presence of local inhomogeneities in corneal tissue after refractive surgery has an influence on visual performance. Here we focus on the corneal ablation associated with Lasik surgery and its effect on the modulation transfer function (MTF) that we obtained by modifying a personalized Kooijman model. Inhomogeneities induced by the ablation occur in the form of Gaussian-distributed refractive-index variations of a given correlation length. We show how variation of refractive-index deviation and correlation length (size) of the inhomogeneities allows us to obtain pairs of values that are able to achieve a MTF evolution similar to that observed for contrast sensitivity in the same patients. An estimate of the characteristics of the local effects is obtained.

  14. The effects of newly synthesized pyrazole derivatives on formaldehyde-, carrageenan-, and dextran-induced acute paw edema in rats.

    PubMed

    Süleyman, H; Büyükokuroğlu, M E

    2001-10-01

    The antiinflammatory effects of 10 newly synthesized pyrazole derivatives on formaldehyde-induced rat paw edema were investigated. The most effective of them (K-3) was investigated again in dextran- and carrageenan-induced paw edema. In formaldehyde-induced paw edema, K-3 50, 100, and 200 mg/kg p.o. inhibited the edema by 48.9% (p<0.002), 68.7% (p<0.001), and 79.1% (p<0.001), respectively, 3 h after administration. In dextran-induced paw edema, the same dose of K-3 produced 27.1% (p<0.05), 46.8% (p<0.01), and 63.8% (p<0.002) inhibition, respectively. In the carrageenan-induced paw edema test, K-3 100 mg/kg decreased the inflammatory response by 52.0% after 4 h. Acute toxicity studies revealed that K-3 was nontoxic up to an oral dose of 2500 mg/kg. PMID:11642317

  15. Expression of Aquaporin 4 and Breakdown of the Blood-Brain Barrier after Hypoglycemia-Induced Brain Edema in Rats

    PubMed Central

    Deng, Jiangshan; Zhao, Fei; Yu, Xiaoyan; Zhao, Yuwu; Li, Dawei; Shi, Hong; Sun, Yongning

    2014-01-01

    Background Hypoglycemia-induced brain edema is a severe clinical event that often results in death. The mechanisms by which hypoglycemia induces brain edema are unclear. Methods In a hypoglycemic injury model established in adult rats, brain edema was verified by measuring brain water content and visualizing water accumulation using hematoxylin and eosin staining. Temporal expression of aquaporin 4 (AQP4) and the integrity of the blood-brain barrier (BBB) were evaluated. We assessed the distribution and expression of AQP4 following glucose deprivation in astrocyte cultures. Results Brain edema was induced immediately after severe hypoglycemia but continued to progress even after recovery from hypoglycemia. Upregulation of AQP4 expression and moderate breakdown of the BBB were observed 24 h after recovery. In vitro, significant redistribution of AQP4 to the plasma membrane was induced following 6 h glucose deprivation. Conclusion Hypoglycemia-induced brain edema is caused by cytotoxic and vasogenic factors. Changes in AQP4 location and expression may play a protective role in edema resolution. PMID:25264602

  16. Laser-induced corneal cross-linking upon photorefractive ablation with riboflavin

    PubMed Central

    Kornilovskiy, Igor M; Kasimov, Elmar M; Sultanova, Ayten I; Burtsev, Alexander A

    2016-01-01

    Aim To estimate the biomechanical effect of the laser-induced cross-linking resulting from photorefractive ablation of the cornea with riboflavin. Methods Excimer laser ablation studies were performed ex vivo (32 eyes of 16 rabbits) by phototherapeutic keratectomy (PTK) and in vivo (24 eyes of 12 rabbits) by transepithelial photorefractive keratectomy (TransPRK), with and without riboflavin saturation of the stroma. Then, we performed corneal optical coherence tomography on 36 eyes of 18 patients with varying degrees of myopia at different times after the TransPRK was performed with riboflavin saturation of the stroma. Results Biomechanical testing of corneal samples saturated with riboflavin revealed cross-linking effect accompanied by the increase in tensile strength and maximum strength. PTK showed increase in tensile strength from 5.1±1.4 to 7.2±1.6 MPa (P=0.001), while Trans-PRK showed increase in tensile strength from 8.8±0.9 to 12.8±1.3 MPa (P=0.0004). Maximum strength increased from 8.7±2.5 to 12.0±2.8 N (P=0.005) in PTK and from 12.8±1.6 to 18.3±1.2 N (P=0.0004) in TransPRK. Clinical optical coherence tomography studies of the biomicroscopic transparent cornea at different times after TransPRK showed increased density in the surface layers of the stroma and membrane-like structure beneath the epithelium. Conclusion Photorefractive ablation of the preliminary corneal stroma saturation with riboflavin causes the effect of laser-induced cross-linking, which is attended with an increase in corneal tensile strength, maximum strength, increased density in the surface layers of the stroma, and formation of a membrane-like structure beneath the epithelium after TransPRK. PMID:27099467

  17. Uncovering the profile of mutations of transforming growth factor beta-induced gene in Chinese corneal dystrophy patients

    PubMed Central

    Hao, Xiao-Dan; Zhang, Yang-Yang; Chen, Peng; Li, Su-Xia; Wang, Ye

    2016-01-01

    AIM To uncover the mutations profile of transforming growth factor beta-induced (TGFBI) gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS Forty-two subjects (6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients) of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy (GCD) (including 3 families and 8 sporadic patients) and lattice corneal dystrophy (LCD) (including 2 families and 9 sporadic patients). The next phenotypes were corneal dystrophy of Bowman layer (CDB) (1 family and 1 sporadic patient) and epithelial basement membrane dystrophy (EBMD) (1 sporadic patient). Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient. CONCLUSION GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD. Our findings extend the mutational spectrum of TFGBI, and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population. PMID:26949635

  18. Edema induced by Bothrops asper (Squamata: Viperidae) snake venom and its inhibition by Costa Rican plant extracts.

    PubMed

    Badilla, Beatriz; Chaves, Fernando; Mora, Gerardo; Poveda, Luis J

    2006-06-01

    We tested the capacity of leaf (Urera baccifera, Loasa speciosa, Urtica leptuphylla, Chaptalia nutans, and Satureja viminea) and root (Uncaria tomentosa) extracts to inhibit edema induced by Bothrops asper snake venom. Edema-forming activity was studied plethysmographically in the rat hind paw model. Groups of rats were injected intraperitoneally with various doses of each extract and, one hour later, venom was injected subcutaneously in the right hind paw. Edema was assessed at various time intervals. The edematogenic activity was inhibited in those animals that received an injection U. tomentosa, C. nutans or L. speciosa extract. The extract of U. baccifera showed a slight inhibition of the venom effect. Extract from S. viminea and, to a lesser extent that of U. leptuphylla, induced a pro-inflammatory effect, increasing the edema at doses of 250 mg/kg at one and two hours. PMID:18494294

  19. Comparison of genome-wide gene expression in suture- and alkali burn-induced murine corneal neovascularization

    PubMed Central

    Jia, Changkai; Zhu, Wei; Ren, Shengwei; Xi, Haijie; Li, Siyuan

    2011-01-01

    Purpose Suture placement and alkali burn to the cornea are often used to induce inflammatory corneal neovascularization (CorNV) models in animals. This study compares the changes in genome-wide gene expression under these two CorNV conditions in mice. Methods CorNV were induced in Balb/c mice by three interrupted 10–0 sutures placed at sites about 1 mm from the corneal apex, or by alkali burns that were 2 mm in size in the central area of the cornea. At the points in time when neovascularization progressed most quickly, some eyeballs were subjected to histological staining to examine CorNV and inflammatory cells infiltration, and some corneas were harvested to extract mRNA for microarray assay. After normalization and filtering, the microarray data were subject to statistical analysis using Significance Analysis of Microarray software, and interested genes were annotated using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) program. The expression change of classical proangiogenic molecule like vascular endothelial growth factor (VEGF) and antiangiogenic molecule like pigment epithelium-derived factor (PEDF) was further verified using western blotting. Results Suture placement induced CorNV in the areas between the suture and limbus, but did not affect the transparency of the yet unvasuclarized areas of the corneas. In contrast, alkali burn caused edema and total loss of transparency of the whole cornea. Histology showed that sutures only caused localized epithelial loss and inflammatory infiltration between the suture and limbus, but chemical burn depleted the whole epithelial layer of the central cornea and caused heavy cellular infiltration of the whole cornea. At day 5 after suture placement, 1,055 differentially expressed probes were identified, out of which 586 probes were upregulated and 469 probes were downregulated. At a comparable time point, namely on day 6 after the alkali burn to the corneas, 472 probes were upregulated

  20. Keratocytes are induced to produce collagen type II: A new strategy for in vivo corneal matrix regeneration.

    PubMed

    Greene, Carol Ann; Green, Colin R; Dickinson, Michelle E; Johnson, Virginia; Sherwin, Trevor

    2016-09-10

    The stroma, the middle layer of the cornea, is a connective tissue making up most of the corneal thickness. The stromal extracellular matrix (ECM) consists of highly organised lamellae which are made up of tightly packed fibrils primarily composed of collagens type I and V. This layer is interspersed with keratocytes, mesenchymal cells of neural crest origin. We have previously shown that adult corneal keratocytes exhibit phenotypic plasticity and can be induced into a neuronal phenotype. In the current study we evaluated the potential of keratocytes to produce collagen type II via phenotypic reprogramming with exogenous chondrogenic factors. The cornea presents a challenge to tissue engineers owing to its high level of organisation and the phenotypic instability of keratocytes. Traditional approaches based on a scar model do not support the engineering of functional stromal tissue. Type II collagen is not found in the adult cornea but is reported to be expressed during corneal development, raising the possibility of using such an approach to regenerate the corneal ECM. Keratocytes in culture and within intact normal and diseased tissue were induced to produce collagen type II upon treatment with transforming growth factor Beta3 (TGFβ3) and dexamethasone. In vivo treatment of rat corneas also resulted in collagen type II deposition and a threefold increase in corneal hardness and elasticity. Furthermore, the treatment of corneas and subsequent deposition of collagen type II did not cause opacity, fibrosis or scarring. The induction of keratocytes with specific exogenous factors and resulting deposition of type II collagen in the stroma can potentially be controlled by withdrawal of the factors. This might be a promising new approach for in vivo corneal regeneration strategies aimed at increasing corneal integrity in diseases associated with weakened ectatic corneal tissue such as keratoconus. PMID:27539660

  1. Pulmonary edema

    MedlinePlus

    ... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

  2. Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats

    PubMed Central

    Akella, Aparna; Tiwari, Anil K.; Rai, Om P.; Deshpande, Shripad B.

    2016-01-01

    Objective: Pulmonary edema, a manifestation of scorpion envenomation syndrome, is attributed to cardiogenic or noncardiogenic factors. Morphine is a drug used for cardiogenic pulmonary edema and its effect on Mesobuthus tamulus (MBT) venom-induced changes is not known. Therefore, we hypothesized that morphine blocks the MBT venom-induced augmentation of phenyldiguanide (PDG) reflex and pulmonary edema. Materials and Methods: Experiments were performed on anesthetized adult female rats. Trachea and jugular vein were cannulated, and the electrocardiographic potentials were recorded by connecting needle electrodes in limb lead II configuration. PDG (10 ΅g/kg, IV, bolus injection) responses were elicited by bolus injection initially, after saline/morphine (1 mg/kg) and after injecting MBT venom (100 μg/kg). The time-response area of the PDG-induced bradycardiac response after treatment was calculated as % of the initial PDG response area. At the end of experiments, lungs were excised for determination of pulmonary water content. Results: PDG produced bradycardiac response that lasted for >60 s. MBT venom augmented the PDG reflex response by 2.5 times. In morphine pretreated group, augmentation of bradycardiac response induced by MBT venom was absent. MBT venom increased the pulmonary water content, and the increase was absent in morphine pretreated animals. Conclusion: The results reveal that morphine prevents the MBT venom-induced augmentation of PDG reflex response and pulmonary edema. Thus, morphine can be useful in scorpion envenomation syndrome associated with pulmonary edema. PMID:26997727

  3. A Novel Zebrafish Model to Provide Mechanistic Insights into the Inflammatory Events in Carrageenan-Induced Abdominal Edema

    PubMed Central

    Huang, Shi-Ying; Feng, Chien-Wei; Hung, Han-Chun; Chakraborty, Chiranjib; Chen, Chun-Hong; Chen, Wu-Fu; Jean, Yen-Hsuan; Wang, Hui-Min David; Sung, Chun-Sung; Sun, Yu-Min; Wu, Chang-Yi; Liu, Wangta; Hsiao, Chung-Der; Wen, Zhi-Hong

    2014-01-01

    A suitable small animal model may help in the screening and evaluation of new drugs, especially those from natural products, which can be administered at lower dosages, fulfilling an urgent worldwide need. In this study, we explore whether zebrafish could be a model organism for carrageenan-induced abdominal edema. The research results showed that intraperitoneal (i.p.) administration of 1.5% λ-carrageenan in a volume of 20 µL significantly increased abdominal edema in adult zebrafish. Levels of the proinflammatory proteins tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) were increased in carrageenan-injected adult zebrafish during the development of abdominal edema. An associated enhancement was also observed in the leukocyte marker, myeloperoxidase (MPO). To support these results, we further observed that i.p. methylprednisolone (MP; 1 µg), a positive control, significantly inhibited carrageenan-induced inflammation 24 h after carrageenan administration. Furthermore, i.p. pretreatment with either an anti-TNF-α antibody (1∶5 dilution in a volume of 20 µL) or the iNOS-selective inhibitor aminoguanidine (AG; 1 µg) inhibited carrageenan-induced abdominal edema in adult zebrafish. This new animal model is uncomplicated, easy to develop, and involves a straightforward inducement of inflammatory edema for the evaluation of small volumes of drugs or test compounds. PMID:25141004

  4. Micropatterned Macrophage Analysis Reveals Global Cytoskeleton Constraints Induced by Bacillus anthracis Edema Toxin

    PubMed Central

    Trescos, Yannick; Tessier, Emilie; Rougeaux, Clémence; Goossens, Pierre L.

    2015-01-01

    Bacillus anthracis secretes the edema toxin (ET) that disrupts the cellular physiology of endothelial and immune cells, ultimately affecting the adherens junction integrity of blood vessels that in turn leads to edema. The effects of ET on the cytoskeleton, which is critical in cell physiology, have not been described thus far on macrophages. In this study, we have developed different adhesive micropatterned surfaces (L and crossbow) to control the shape of bone marrow-derived macrophages (BMDMs) and primary peritoneal macrophages. We found that macrophage F-actin cytoskeleton adopts a specific polar organization slightly different from classical human HeLa cells on the micropatterns. Moreover, ET induced a major quantitative reorganization of F-actin within 16 h with a collapse at the nonadhesive side of BMDMs along the nucleus. There was an increase in size and deformation into a kidney-like shape, followed by a decrease in size that correlates with a global cellular collapse. The collapse of F-actin was correlated with a release of focal adhesion on the patterns and decreased cell size. Finally, the cell nucleus was affected by actin reorganization. By using this technology, we could describe many previously unknown macrophage cellular dysfunctions induced by ET. This novel tool could be used to analyze more broadly the effects of toxins and other virulence factors that target the cytoskeleton. PMID:26015478

  5. Exercise-induced interstitial pulmonary edema at sea-level in young and old healthy humans

    PubMed Central

    Taylor, Bryan J.; Carlson, Alex R.; Miller, Andrew D.; Johnson, Bruce D.

    2014-01-01

    We asked whether aged adults are more susceptible to exercise-induced pulmonary edema relative to younger individuals. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (Dm) and pulmonary-capillary blood volume (Vc) were measured before and after exhaustive discontinuous incremental exercise in 10 young (YNG; 27±3 yr) and 10 old (OLD; 69±5 yr) males. In YNG subjects, Dm increased (11±7%, P=0.031), Vc decreased (−10±9%, P=0.01) and DLCO was unchanged (30.5±4.1 vs. 29.7±2.9 ml/min/mmHg, P=0.44) pre- to post-exercise. In OLD subjects, DLCO and Dm increased (11±14%, P=0.042; 16±14%, P=0.025) but Vc was unchanged (58±23 vs. 56±23 ml, P=0.570) pre- to post-exercise. Group-mean Dm/Vc was greater after vs. before exercise in the YNG and OLD subjects. However, Dm/Vc was lower post-exercise in 2 of the 10 YNG (−7±4%) and 2 of the 10 OLD subjects (−10±5%). These data suggest that exercise decreases interstitial lung fluid in most YNG and OLD subjects, with a small number exhibiting evidence for exercise-induced pulmonary edema. PMID:24200644

  6. beta-Lapachone reduces endotoxin-induced macrophage activation and lung edema and mortality.

    PubMed

    Tzeng, Huei-Ping; Ho, Feng-Ming; Chao, Kuo-Fang; Kuo, Min-Liang; Lin-Shiau, Shoei-Yn; Liu, Shing-Hwa

    2003-07-01

    beta-Lapachone, a 1,2-naphthoquinone, is a novel chemotherapeutic agent. It has been shown to be capable of suppressing inducible nitric oxide synthase expression and function in rat alveolar macrophages. The authors further performed experiments to examine the molecular mechanism of beta-lapachone on LPS-induced responses in rat alveolar macrophages and to evaluate its in vivo antiinflammatory effect. A significant increase in nitrite production and inducible nitric oxide synthase expression was elicited in macrophages treated with LPS that was inhibited by coincubation with beta-lapachone. beta-Lapachone could also inhibit the production of tumor necrosis factor-alpha induced by LPS. LPS induces protein tyrosine phosphorylation and nuclear factor-kappaB binding activity by gel mobility shift assay in macrophages. These events were significantly inhibited by beta-lapachone. Furthermore, beta-lapachone in vivo protected against the induction of lung edema, lung-inducible nitric oxide synthase protein expression and nuclear factor-kappaB activation, lethality, and increased plasma nitrite and serum tumor necrosis factor-alpha levels induced by LPS. These results indicate that beta-lapachone suppresses inducible nitric oxide synthase induction and tumor necrosis factor-alpha production mediated by the inhibition of protein tyrosine phosphorylation and nuclear factor-kappaB activation caused by LPS. This results in a beneficial effect in an animal model of sepsis. PMID:12724123

  7. Corneal Disorders

    MedlinePlus

    ... Injuries Dystrophies - conditions in which parts of the cornea lose clarity due to a buildup of cloudy material Treatments of corneal disorders include medicines, corneal transplantation, and corneal laser surgery. NIH: National Eye Institute

  8. Decrease in hyperosmotic stress–induced corneal epithelial cell apoptosis by L-carnitine

    PubMed Central

    Khandekar, Neeta; Willcox, Mark D.P.; Shih, Sharon; Simmons, Peter; Vehige, Joseph

    2013-01-01

    Purpose To characterize the osmoprotective properties of L-carnitine on human corneal epithelial cell volume and apoptosis during hyperosmotic stress. Methods Human corneal limbal epithelial (HCLE) cells were exposed to culture medium at 300 mOsm (isotonic) or 500 mOsm (hyperosmotic) with or without L-carnitine (10 mM). Induction of apoptosis was detected by quantifying the proteolytic activity of caspase-8, caspase-9, and caspase-3/7 using caspase activity assays, the expression of tumor necrosis factor (TNF)-α with enzyme-linked immunosorbent assay, and annexin V/propidium iodide staining of HCLE cells evaluated with confocal microscopy and flow cytometry. Cell volume changes in response to hyperosmotic stress were analyzed using flow cytometry. Results After the HCLE cells were exposed to hyperosmotic medium (500 mOsm), the percentage of shrunken cells and damaged/dead cells (stained positively for annexin V and/or propidium iodide) was six- and three-fold, respectively, higher than that under isotonic conditions (300 mOsm). This was paralleled by an increase in TNF-α concentration in media and caspase-8, -9, and -3/7 activities (six-, four-, ten-, and twelve-fold, respectively; all showing p<0.001). Addition of L-carnitine during hyperosmotic stress partly restored cell volume and significantly reduced the concentration of TNF-α released (p=0.005) and caspase-9 activity (p=0.0125). Addition of L-carnitine reduced the percentage of hyperosmolarity-induced damaged/dead cells to levels observed under isotonic conditions. Conclusions L-carnitine can regulate human corneal epithelial cell volume under hyperosmotic stress and ameliorate hyperosmotic stress–induced apoptosis. PMID:24068862

  9. Treatment of tyramine-induced brain edema with anion transport inhibitor L-644,711

    SciTech Connect

    Faraj, B.A.; Cragoe, E.J. Jr.; Sarper, R.; Camp, M.; Malveaux, E.

    1988-01-01

    Tyramine induces coma in phenelzine-treated dogs. Development of coma in these animals is associated with brain edema, abnormal brain scans of Tc-99m-diethylene-triamine-penta-acetic acid (Tc-99m-DTPA), and elevated levels of CSF catecholamines. We found that the intravenous administration of 6-7 mg/kg of a single dose of L-644,711 given fifteen minutes after the oral administration of tyramine to phenelzine-pretreated animals followed by an infusion of normal saline containing 6-7 mg/kg of the drug given over a period of 2 hr caused reversal of brain injury. This was accompanied by full recovery within a period of 24 hr of all the animals tested. A follow-up study revealed that 24 hr after treatment with L-644,711 CSF levels of catecholamines and brain images of Tc-99m-DTPA were indistinguishable from normal controls. Animals that received no drug died from unresolved coma within 4 to 24 hr. Animals that had recovered due to therapy with L-644,711 were given 10-14 days rest followed by a repetition of the phenelzine and tyramine treatment but denied L-644,711 therapy. These animals also died of unresolved coma within 24 hr. This preliminary study suggest that the use of L-644,711 may constitute an important advance in treatment of brain edema of a wide range of neurological disorders.

  10. Brain natriuretic peptide levels in six basic underwater demolitions/SEAL recruits presenting with swimming induced pulmonary edema (SIPE).

    PubMed

    Shearer, Damon; Mahon, Richard

    2009-01-01

    Swimming induced pulmonary edema (SIPE) is associated with both SCUBA diving and strenuous surface swimming; however, the majority of reported cases and clinically observed cases tend to occur during or after aggressive surface swimming. Capillary stress failure appears to be central to the pathophysiology of this disorder. Regional pulmonary capillaries are exposed to relatively high pressures secondary to increased vascular volume, elevation of pulmonary vascular resistance, and regional differences in perfusion secondary to forces of gravity and high cardiac output. Acute pulmonary edema can be classified as either cardiogenic or noncardiogenic or both. Cardiogenic pulmonary edema occurs when the pulmonary capillary hydrostatic pressure exceeds plasma oncotic pressure. Noncardiogenic pulmonary edema occurs when pulmonary capillary permeability is increased. Given the pathophysiology noted above, SIPE can be described as a cardiogenic pulmonary edema, at least in part, since an increased transalveolar pressure gradient has been implicated in the pathogenesis of SIPE. Brain natriuretic peptide (BNP) is used in the clinical setting to differentiate cardiac from pulmonary sources of dyspnea, specifically to diagnose cardiogenic pulmonary edema. During clinical management, BNP levels were drawn on six BUD/S recruits simultaneously presenting with pulmonary complaints consistent with SIPE, after an extended surface bay swim. This paper analyzes that data after de-identification and reviews the pathophysiology and clinical management of SIPE. PMID:19739476

  11. Photorepair of ultraviolet radiation-induced pyrimidine dimers in corneal DNA.

    PubMed

    Ley, R D; Applegate, L A; Freeman, S E

    1988-07-01

    The induction and photorepair of pyrimidine dimers in DNA have been measured in the ultraviolet-irradiated, corneal epithelium of the marsupial, Monodelphis domestica, using damage-specific nucleases from Micrococcus luteus in conjunction with agarose gel electrophoresis. We observed that FS-40 sunlamps (280-400 nm) induced 7.2 +/- 1.0 X 10(-5) pyrimidine dimers per kilobase (kb) of DNA per J/m2. Following 100 J/m2, 50% and greater than 90% of the dimers were photorepaired during a 10- and 30-min exposure to photoreactivating light (320-400 nm), respectively. In addition, approximately 70% and approximately 60% of the dimers induced by 300 and 500 J/m2, respectively, were repaired by a 60-min exposure to photoreactivating light. The capacity of the corneal epithelium of M. domestica to photorepair pyrimidine dimers identifies this animal as a potentially useful model with which to determine whether pyrimidine dimers are involved in pathological changes of the irradiated eye. PMID:3386657

  12. Platelet-activating factor induces collagenase expression in corneal epithelial cells.

    PubMed Central

    Bazan, H E; Tao, Y; Bazan, N G

    1993-01-01

    Platelet-activating factor (PAF), a potent lipid mediator involved in inflammatory and immune responses, accumulates rapidly in response to injury in a variety of tissues, including the corneal epithelium. However, the precise role of this compound in the cascade of events following insult has not been defined. Here we examined the effect of PAF on gene expression in the epithelial cells of rabbit corneas in organ culture. We found that incubation with 100 nM methylcarbamoyl PAF, a nonhydrolyzable analog of PAF, produced rapid transient 2.8- and 3.5-fold increases in the expression of c-fos and c-jun, respectively, at 1 hr, followed by increased expression of the collagenase type I gene beginning at 3 hr and peaking at 14-fold by 8 hr. Addition of the protein-synthesis-inhibitor cycloheximide superinduced c-fos and c-jun, strongly potentiating the PAF effect, but inhibited the induction of collagenase type I expression, suggesting the existence of a transcriptional factor linking the two events. BN-50730, a selective antagonist of intracellular PAF-binding sites, blocked the expression of the immediate-early genes as well as the increase in collagenase type I mRNA. Our results suggest that one of the functions of PAF may be to enhance the breakdown of the extracellular matrix as a part of the remodeling process during corneal wound healing after injury. Pathologically, a PAF-induced overproduction of collagenase may be a factor in the development of corneal ulcers, as well as other pathophysiological conditions such as cartilage destruction in arthritis. If so, inhibitors of this signal-transduction pathway may be useful as tools for further investigation and, eventually, as therapeutic agents to treat such disorders. Images Fig. 1 Fig. 2 PMID:8378347

  13. Reversible Corneal Toxicity of Retained Intracameral Perfluoro-n-octane

    PubMed Central

    Alharbi, Saad S.; Asiri, Mohammed S.

    2016-01-01

    A 58-year-old female presented with intracameral retained perfluoro-n-octane (PFO) following previous retinal reattachment surgery. After 4 years of follow-up without related sequelae, the patient complained of a gradual decrease in vision secondary to corneal edema with whitish corneal precipitate inferiorly corresponding to the area of retained PFO. Three weeks after anterior chamber washout, corneal edema resolved and the patient obtained 20/40 visual acuity. Even though PFO considered to have a relatively good safety profile, early anterior chamber washout may prevent corneal toxicity and avoid later persistent corneal decompensation. PMID:27555718

  14. Reversible Corneal Toxicity of Retained Intracameral Perfluoro-n-octane.

    PubMed

    Alharbi, Saad S; Asiri, Mohammed S

    2016-01-01

    A 58-year-old female presented with intracameral retained perfluoro-n-octane (PFO) following previous retinal reattachment surgery. After 4 years of follow-up without related sequelae, the patient complained of a gradual decrease in vision secondary to corneal edema with whitish corneal precipitate inferiorly corresponding to the area of retained PFO. Three weeks after anterior chamber washout, corneal edema resolved and the patient obtained 20/40 visual acuity. Even though PFO considered to have a relatively good safety profile, early anterior chamber washout may prevent corneal toxicity and avoid later persistent corneal decompensation. PMID:27555718

  15. Spontaneous remission of edema and regranulation of goblet cells in rat tracheae after capsaicin-induced acute inflammation.

    PubMed

    Guo, Jin-Jang; Wang, Di-Seng; Huang, Hung-Tu

    2003-03-01

    baseline level. Seven days after capsaicin, the edema ratio was similar to the controls. The number of goblet cells was even larger than controls. It is concluded that capsaicin-induced acute inflammation in the rat trachea involves formation of endothelial gaps, extensive plasma extravasation and edema formation, and depletion of goblet-cell secretory granules. Spontaneous gradual remission of edema was accompanied by regranulation of goblet cells with gradual mucogenesis for several days. PMID:12649728

  16. Anti-Inflammatory Activity of Lactobacillus on Carrageenan-Induced Paw Edema in Male Wistar Rats

    PubMed Central

    Amdekar, Sarika; Roy, Purabi; Singh, Vinod; Kumar, Avnish; Singh, Rambir; Sharma, Poonam

    2012-01-01

    Introduction. Lactobacillus casei and Lactobacillus acidophilus were used to assess the anti-inflammatory properties in carrageenan induced acute inflammatory model. Materials and Methods. Diclofenac sodium was used as standard drug at concentration of 150 mg/kg of body weight. Culture of Lactobacillus  2 × 107 CFU/ml was given orally. Edema was induced with 1% carrageenan to all the groups after one hour of the oral treatments. Paw thickness was checked at t = 1, 2, 3, 4, 5, and 24 hours. Stair climbing score and motility score were assessed at t = 24 hours. Cytokines assay for IL-6, IL-10, and TNF-α was performed on serum samples. Results. Lactobacillus showed a statistically significant decrease in paw thickness at P < 0.001. L. acidophilus and L. casei decreased by 32% and 28% in paw thickness. They both significantly increased the stair climbing and motility score. Lactobacillus treatment significantly downregulated IL-6 and TNF-α while upregulated IL-10 at P < 0.0001. Conclusion. L. casei and L. acidophilus significantly decreased the inflammatory reactions induced by carrageenan. This study has also proposed that Lactobacillus ameliorated the inflammatory reaction by downregulating the proinflammatory cytokines pathway. PMID:22518342

  17. Platelet-activating factor-induced pulmonary edema is partly mediated by prostaglandin E(2), E-prostanoid 3-receptors, and potassium channels.

    PubMed

    Göggel, Rolf; Hoffman, Sven; Nüsing, Rolf; Narumiya, Suh; Uhlig, Stefan

    2002-09-01

    Platelet-activating factor (PAF) is an important endogenous mediator of pulmonary edema in many models of acute lung injury. PAF triggers edema formation by simultaneous activation of two independent pathways; one is mediated by a cyclooxygenase metabolite, and the other is blocked by quinine. We examined the hypothesis that the cyclooxygenase-dependent part of PAF-induced edema is mediated by prostaglandin E(2) (PGE(2)). In isolated rat lungs, PAF administration stimulated release of PGE(2) into the venous effluate and increased lung weight as a measure of edema formation. Perfusion with a neutralizing PGE(2) antibody attenuated the PAF-induced edema formation. In vivo, E-prostanoid 3-receptor-deficient mice showed less pulmonary Evans blue extravasation in response to PAF injection than did mice deficient in EP1, EP2, or EP4 receptors. Perfusion of rat lungs with PGE(2) caused pulmonary edema, which was largely prevented by inhibition of voltage-gated potassium channels (25 nM beta-dendrotoxin), but not by blocking calcium-dependent potassium currents (100 micro M paxilline). In line with its effects on PGE(2)-induced edema formation, beta-dendrotoxin attenuated PAF-induced edema partly if given alone, and completely in combination with quinine. Our findings suggest that PAF-triggered edema is partly mediated by the release of PGE(2), activation of EP3 receptors, and activation of voltage-gated potassium channels. PMID:12204861

  18. Assessment of therapeutic options for reducing alkali burn-induced corneal neovascularization and inflammation.

    PubMed

    Bakunowicz-Łazarczyk, Alina; Urban, Beata

    2016-03-01

    This article aims to review and provide the current knowledge of the possibilities of topical treatment of corneal neovascularization due to alkali burns, evidenced by laboratory experiments, in vitro studies, and clinical trials published in the specialized literature. Authors present clinically relevant treatment of corneal neovascularization used in clinical practice, potential antiangiogenic topical therapeutics against corneal neovascularization, which are under investigation, and anti-angiogenic gene-therapy. PMID:26651127

  19. Retained IOL fragment and corneal decompensation after pseudophakic IOL exchange.

    PubMed

    Hoffman, Richard S; Fine, I Howard; Packer, Mark

    2004-06-01

    A 72-year-old man had exchange of a foldable silicone multifocal intraocular lens (IOL) by transection, removal, and monofocal IOL replacement. One month after the exchange, irreversible corneal edema developed and penetrating keratoplasty was performed. At the time of the corneal transplant, a small silicone fragment was discovered in and removed from the anterior chamber. Histologic evaluation of the patient's cornea demonstrated an absence of corneal endothelium, suggesting the fragment was the etiology of the corneal decompensation. PMID:15177618

  20. Effect of Fenoterol on PAF-induced lung edema in isolated and perfused rabbit lungs.

    PubMed

    Pesce, L; Tristano, S; Friedman, E; Comellas, A; Marcano, H; Sanchez de León, R

    1998-11-01

    We have studied the effects of fenoterol on PAF-induced response in pulmonary circulation. We used 28 isolated and perfused rabbit lungs preparations: eight control preparations (CP), four vehicles preparations (VP), eight PAF preparations (PP) with two doses of PAF, one called low dose (LD = 0.5 microg/kg of weight) and the other high dose (HD = 1 microg/kg of weight) and eight Fenoterol preparations (FP) which we administered 0.05 mg of Fenoterol for 15 min, followed by a LD and HD of PAF. FP prevented elevation of pulmonary artery pressure (Ppa) as compared to PP, at LD of PAF: 12.615 (CI 95%: 8.57-20.885) versus 83.705 (CI 95%: 50.55-114.3) cm of water; and at HD of PAF: 19.38 (CI 95%: 11.235-28.94) versus 205.1 (CI 95%: 141.3-271) cm of water respectively. FP prevented the increase in fluid filtration rate (FFR) observed in PP at both doses of PAF LD: 0.765 (CI 95%: 0.07-3.385) versus 0.01 (CI 95%: -0.05-0.005) g/min; HD: 5.515 (CI 95%: 2.425-8.865) versus 0.03 (CI 95%: 0-0.33) g/min. Our results suggest that PAF has a vasoconstrictor effect that produces lung edema and this effect is inhibited by fenoterol. PMID:9865589

  1. Anti-inflammatory potential of probiotic Lactobacillus spp. on carrageenan induced paw edema in Wistar rats.

    PubMed

    Archer, Ann Catherine; Muthukumar, S P; Halami, Prakash M

    2015-11-01

    The aim of the present study was to evaluate the anti-inflammatory ability of novel indigenous probiotic Lactobacillus fermentum MCC 2759, L. fermentum MCC 2760 and Lactobacillus delbrueckii MCC 2775 in a carrageenan induced acute inflammatory paw edema model. Probiotic cultures were administered to male Wistar rats via oral route. Carrageenan at a concentration of 1% was injected into hind paw of rats 30min after oral gavage on the 8th day of treatment regimen. Paw thickness (mm), stair climbing activity and motility score were the parameters used to score the inflammatory response. L. fermentum MCC 2759, L. fermentum MCC 2760 and L. delbrueckii MCC 2775 showed significant reduction in paw thickness (P<0.05) showing percentage inhibition of 15.67%, 14.72% and 14.84%, respectively, 24h after carrageenan induction. Probiotic treatment also markedly alleviated the stair climbing and motility score. Histological analysis of tissue sections revealed reduction in cellular infiltration of probiotic and drug treatment groups. Adhesion to resected rat intestinal tissue also showed significant adherence capability (>40%) of the probiotic cultures used. Therefore, L. fermentum MCC 2759, L. fermentum MCC 2760 and L. delbrueckii MCC 2775 may be used as potent anti-inflammatory agents with probiotic health benefits. PMID:26314910

  2. CD147 Required for Corneal Endothelial Lactate Transport

    PubMed Central

    Li, Shimin; Nguyen, Tracy T.; Bonanno, Joseph A.

    2014-01-01

    Purpose. CD147/basigin is a chaperone for lactate:H+ cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. Methods. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. Results. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. Conclusions. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. PMID:24970254

  3. Gabapentin induces edema, hyperesthesia and scaling in a depressed patient; a diagnostic challenge

    PubMed Central

    Bidaki, Reza; Sadeghi, Zahra; Shafizadegan, Safiye; Sadeghi, Ali; Khalili, Behrang; Haghshenas, Alireza; Mirhosseini, Seyyed Mohammad Mahdy

    2016-01-01

    Gabapentin is a common drug used as analgesic and anticonvulsant and also is prescribed for insomnia, depression, obsessive – compulsive disorder and panic attack. We report a case of a 48-year-old man who is prescribed gabapentin because of insomnia, headache, and depressed mood. In the first period of using the drug no complication has been seen. However in the next period, side-effects such as hyperesthesia, scaling and severe localized edema has been observed. After several laboratory tests and imaging, no reason was found for his edema. And after discontinuing gabapentin the pain and edema was quite relieved. We found out the brand of the drug has been switched in the second stage. The point which makes our study special is the incidence of side-effects such as severe edema, scaling and hyperesthesia for the first time because of using gabapentin and changing the drug combination. PMID:26955622

  4. Gabapentin induces edema, hyperesthesia and scaling in a depressed patient; a diagnostic challenge.

    PubMed

    Bidaki, Reza; Sadeghi, Zahra; Shafizadegan, Safiye; Sadeghi, Ali; Khalili, Behrang; Haghshenas, Alireza; Mirhosseini, Seyyed Mohammad Mahdy

    2016-01-01

    Gabapentin is a common drug used as analgesic and anticonvulsant and also is prescribed for insomnia, depression, obsessive - compulsive disorder and panic attack. We report a case of a 48-year-old man who is prescribed gabapentin because of insomnia, headache, and depressed mood. In the first period of using the drug no complication has been seen. However in the next period, side-effects such as hyperesthesia, scaling and severe localized edema has been observed. After several laboratory tests and imaging, no reason was found for his edema. And after discontinuing gabapentin the pain and edema was quite relieved. We found out the brand of the drug has been switched in the second stage. The point which makes our study special is the incidence of side-effects such as severe edema, scaling and hyperesthesia for the first time because of using gabapentin and changing the drug combination. PMID:26955622

  5. Aplastic anemia induced disc edema and visual loss in pregnancy: a case report

    PubMed Central

    Gupta, Shailesh K; Brar, Vikram S; Keshavamurthy, Ravi; Chalam, Kakarla V

    2008-01-01

    Introduction A case of aplastic anemia diagnosed during pregnancy, which developed bilateral disc edema and acute pre-retinal hemorrhage leading to vision loss. Case Presentation A 20 year old primagravid female developed acute vision loss in her right eye, during hospitalization for treatment of aplastic anemia diagnosed during her pregnancy. Her best-corrected visual acuity (BCVA) was hand motions and fundus evaluation revealed a large pre-macular hemorrhage in the right eye (OD) and bilateral disc edema. Neuro-imaging studies did not reveal any signs of intracranial mass lesion or edema. Conclusion There was resolution of the disc edema with improvement in the pre-macular hemorrhage resulting in 20/50 vision in the right eye, following supportive transfusions. Ophthalmic manifestations developing in a pregnant patient with aplastic anemia can be successfully managed with supportive care including red blood cell and platelet transfusions. PMID:19017378

  6. MYELIN BASIC PROTEIN-MESSENGER RNA (MBP-MRNA) EXPRESSION DURING TRIETHYLTIN-INDUCED MYELIN EDEMA

    EPA Science Inventory

    Triethyltin (TET) is a neurotoxicant that produces severe but transient cerebral edema, characterized ultrastructurally by vacuolation of the intraperiod line of central nervous system (CNS) myelin. ET has been reported to depress levels of myelin basic protein (MBP), a glycoprot...

  7. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes.

    PubMed

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  8. HCV core and NS3 proteins mediate toll like receptor induced innate immune response in corneal epithelium.

    PubMed

    Rajalakshmy, Ayilam Ramachandran; Malathi, Jambulingam; Madhavan, Hajib Naraharirao

    2014-11-01

    Direct association of dry eye syndrome and hepatitis C virus (HCV) infection is a well established fact. In this context, the current study examines the in vitro corneal inflammatory response with respect to HCV core and NS3 antigens. Toll like receptors (TLRs) are pattern recognition receptors which can mediate innate immune response. In the present study, corneal epithelial cells responded to HCV core and NS3 proteins by secreting pro-inflammatory cytokines IL-8, IL-6 and TNF-α via TLR1, TLR2 and TLR6 mediated innate immune response. MyD88/NF-kB signalling was involved in pro-inflammatory cytokine production. Corneal epithelium synthesised nitric oxide (NO) via iNOS during HCV core and NS3 exposure. On later stages of inflammation, cells underwent apoptosis which lead to cell death. SiRNA mediated silencing of TLR1, TLR2 and TLR6 resulted in a significant down regulation of IL-8 and NO. In conclusion, this study indicates that HCV core and NS3 proteins are capable of inducing immune response in corneal epithelium which can potentiate the pathology of HCV associated dry eye condition. Blocking specific TLR response can have therapeutic application in controlling the inflammatory response associated with this dry eye condition. PMID:25280963

  9. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes

    PubMed Central

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  10. Lumican induces human corneal epithelial cell migration and integrin expression via ERK 1/2 signaling

    SciTech Connect

    Seomun, Young; Joo, Choun-Ki

    2008-07-18

    Lumican is a major proteoglycans of the human cornea. Lumican knock-out mice have been shown to lose corneal transparency and to display delayed wound healing. The purpose of this study was to define the role of lumican in corneal epithelial cell migration. Over-expression of lumican in human corneal epithelial (HCE-T) cells increased both cell migration and proliferation, and increased levels of integrins {alpha}2 and {beta}1. ERK 1/2 was also activated in lumican over-expressed cells. When we treated HCE-T cells with the ERK-specific inhibitor U0126, cell migration and the expression of integrin {beta}1 were completely blocked. These data provide evidence that lumican stimulates cell migration in the corneal epithelium by activating ERK 1/2, and point to a novel signaling pathway implicated in corneal epithelial cell migration.

  11. Effects of antiperoxidants on FeCl2-induced lipid peroxidation and focal edema in rat brain.

    PubMed

    Willmore, L J; Rubin, J J

    1984-01-01

    Head trauma with contusion or cortical laceration and hemorrhage causes focal edema with encephalomalacia and gliosis. Because cerebral hemorrhage ultimately results in deposition of heme compounds and iron into the neuropil, we injected an aqueous solution of iron salts to simulate the decompartmentalization of iron after trauma. We pretreated animals with saline or with 600 mg/kg alpha-tocopherol plus 5 ppm selenium added to the drinking water. Formation of lipid peroxidation products was significantly inhibited within the iron injection site in the antiperoxidant-pretreated rats at 30, 60, and 120 min after injection of iron into the isocortex. The antiperoxidants failed to prevent formation of focal brain edema at the injection site between 1 and 8 h after injection; however, significantly less edema was present in the alpha-tocopherol + selenium-pretreated animals 24 and 48 h after injection. The efficacy of antiperoxidants in preventing lipid peroxidation, and enhancing the resolution of ferrous-induced focal brain edema suggest that tocopherol + selenium administration caused free radical quenching and termination of lipid peroxidation, and increased membrane stabilization, an effect similar to the action of glucocorticoids. PMID:6690325

  12. Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema

    PubMed Central

    Chen, Shao-Jun; Yang, Jia-Fang; Kong, Fan-Ping; Ren, Ji-Long; Hao, Ke; Li, Min; Yuan, Yuan; Chen, Xin-Can; Yu, Ri-Sheng; Li, Jun-Fa; Leng, Gareth; Chen, Xue-Qun; Du, Ji-Zeng

    2014-01-01

    Cerebral edema is a potentially life-threatening illness, but knowledge of its underlying mechanisms is limited. Here we report that hypobaric hypoxia induces rat cerebral edema and neuronal apoptosis and increases the expression of corticotrophin releasing factor (CRF), CRF receptor type 1 (CRFR1), aquaporin-4 (AQP4), and endothelin-1 (ET-1) in the cortex. These effects, except for the increased expression of CRF itself, could all be blocked by pretreatment with an antagonist of the CRF receptor CRFR1. We also show that, in cultured primary astrocytes: (i) both CRFR1 and AQP4 are expressed; (ii) exogenous CRF, acting through CRFR1, triggers signaling of cAMP/PKA, intracellular Ca2+, and PKCε; and (iii) the up-regulated cAMP/PKA signaling contributes to the phosphorylation and expression of AQP4 to enhance water influx into astrocytes and produces an up-regulation of ET-1 expression. Finally, using CHO cells transfected with CRFR1+ and AQP4+, we show that transfected CRFR1+ contributes to edema via transfected AQP4+. In conclusion, hypoxia triggers cortical release of CRF, which acts on CRFR1 to trigger signaling of cAMP/PKA in cortical astrocytes, leading to activation of AQP4 and cerebral edema. PMID:25146699

  13. Corneal dystrophies

    PubMed Central

    Klintworth, Gordon K

    2009-01-01

    The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The designation is imprecise but remains in vogue because of its clinical value. Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (anterior corneal dystrophies), the corneal stroma (stromal corneal dystrophies), or Descemet membrane and the corneal endothelium (posterior corneal dystrophies). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees. Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Knowledge about the responsible genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases (mucopolysaccharidoses

  14. Hypoxia-induced production of 12-hydroxyeicosanoids in the corneal epithelium: involvement of a cytochrome P-4504B1 isoform.

    PubMed

    Mastyugin, V; Aversa, E; Bonazzi, A; Vafaes, C; Mieyal, P; Schwartzman, M L

    1999-06-01

    The corneal epithelium metabolizes arachidonic acid by a cytochrome P-450 (CYP)-mediated activity to 12-hydroxy-5,8,11, 14-eicosatetraenoic acid (12(R)-HETE) and 12-hydroxy-5,8, 14-eicosatrienoic acid (12(R)-HETrE ). Both metabolites possess potent inflammatory properties, with 12(R)-HETrE being a powerful angiogenic factor, and they assume the role of inflammatory mediators in hypoxia- and chemical-induced injury in the cornea in vivo and in vitro. We used a model of corneal organ culture that exhibits hypoxia-induced epithelial CYP-dependent 12(R)-HETE and 12(R)-HETrE synthesis for isolating, identifying, and characterizing the CYP protein responsible for these eicosanoid syntheses. Northern analysis revealed the presence of a CYP4A-hybridizable mRNA, the levels of which were increased after hypoxia. Reverse transcription-polymerase chain reaction analysis with primers specific for the CYP4A family led to the isolation of a 671-base pair fragment with a 98.8% sequence homology to the rabbit lung CYP4B1 isoform, of which the levels in the corneal epithelium were greatly increased under hypoxic conditions. Moreover, phenobarbital, an inducer of hepatic CYP4B1 in the rabbit, also induced 12-HETE and 12-HETrE synthesis. Antibodies against CYP4B1, but not against CYP4A1, inhibited hypoxia-, clofibrate-, and phenobarbital-induced 12-HETE and 12-HETrE synthesis. These results suggest the involvement of a CYP4B1 isoform in the corneal epithelial synthesis of these eicosanoids in response to hypoxia. PMID:10336559

  15. A 45-Year-Old Man With Recurrent Dyspnea and Hemoptysis during Exercise: Exercise-Induced Pulmonary Hemorrhage/Edema

    PubMed Central

    Kim, Dae Sung; Lee, Minhyeok; Kwon, Oh Jung; Jeong, Inbeom; Son, Ji Woong; Na, Moon Jun

    2015-01-01

    A 45-year-old man presented with dyspnea and hemoptysis during exercise. A chest computed tomography (CT) revealed multifocal diffuse patchy ground glass opacity and interlobular septal thickening in both the lungs. Permeability pulmonary edema or pulmonary hemorrhage was suspected. Serologic studies for autoimmune disorders and vasculitis were negative. There was no laboratory evidence of coagulopathy, other hematopoietic disease or infectious disease. Considering correlation with exercise, we diagnosed exercise-induced pulmonary hemorrhage (EIPH) or exercise-induced pulmonary edema (EIPE). The patient was managed with antifibrinolytics, antibiotics, and antitussive agent. After a week, follow-up chest CT revealed completely resolved pulmonary hemorrhage. About 2 months after the first event, he visited again with dyspnea and hemoptysis during running. In the present study, we report a case of recurrent pulmonary hemorrhage after exercise. PMID:26508928

  16. Quinidine, but Not Eicosanoid Antagonists or Dexamethasone, Protect the Gut from Platelet Activating Factor-Induced Vasoconstriction, Edema and Paralysis

    PubMed Central

    Lautenschläger, Ingmar; Frerichs, Inéz; Dombrowsky, Heike; Sarau, Jürgen; Goldmann, Torsten; Zitta, Karina; Albrecht, Martin; Weiler, Norbert; Uhlig, Stefan

    2015-01-01

    Intestinal circulatory disturbances, atony, edema and swelling are of great clinical relevance, but the related mechanisms and possible therapeutic options are poorly characterized, in part because of the difficulties to comprehensively analyze these conditions. To overcome these limitations we have developed a model of the isolated perfused rat small intestine where all of these symptoms can be studied simultaneously. Here we used this model to study the role of eicosanoids, steroids and quinidine in platelet-activating factor (PAF)-induced intestinal disorders. A vascular bolus of PAF (0.5 nmol) triggered release of thromboxane and peptidoleukotrienes into the vascular bed (peak concentration 35 nM and 0.8 nM) and reproduced all symptoms of intestinal failure: mesenteric vasoconstriction, translocation of fluid and macromolecules from the vasculature to the lumen and lymphatics, intestinal edema formation, loss of intestinal peristalsis and decreased galactose uptake. All effects of PAF were abolished by the PAF-receptor antagonist ABT491 (2.5 μM). The COX and LOX inhibitors ASA and AA861 (500 μM, 10 μM) did not exhibit barrier-protective effects and the eicosanoid antagonists SQ29548 and MK571 (10 μM, each) only moderately attenuated the loss of vascular fluid, the redistribution to the lumen and the transfer of FITC dextran to the lumen. The steroid dexamethasone (10 μM) showed no barrier-protective properties and failed to prevent edema formation. Quinidine (100 μM) inhibited the increase in arterial pressure, stabilized all the intestinal barriers, and reduced lymph production and the transfer of FITC dextran to the lymph. While quinidine by itself reduced peristalsis, it also obviated paralysis, preserved intestinal functions and prevented edema formation. We conclude that quinidine exerts multiple protective effects against vasoconstriction, edema formation and paralysis in the intestine. The therapeutic use of quinidine for intestinal ailments

  17. Quinidine, but not eicosanoid antagonists or dexamethasone, protect the gut from platelet activating factor-induced vasoconstriction, edema and paralysis.

    PubMed

    Lautenschläger, Ingmar; Frerichs, Inéz; Dombrowsky, Heike; Sarau, Jürgen; Goldmann, Torsten; Zitta, Karina; Albrecht, Martin; Weiler, Norbert; Uhlig, Stefan

    2015-01-01

    Intestinal circulatory disturbances, atony, edema and swelling are of great clinical relevance, but the related mechanisms and possible therapeutic options are poorly characterized, in part because of the difficulties to comprehensively analyze these conditions. To overcome these limitations we have developed a model of the isolated perfused rat small intestine where all of these symptoms can be studied simultaneously. Here we used this model to study the role of eicosanoids, steroids and quinidine in platelet-activating factor (PAF)-induced intestinal disorders. A vascular bolus of PAF (0.5 nmol) triggered release of thromboxane and peptidoleukotrienes into the vascular bed (peak concentration 35 nM and 0.8 nM) and reproduced all symptoms of intestinal failure: mesenteric vasoconstriction, translocation of fluid and macromolecules from the vasculature to the lumen and lymphatics, intestinal edema formation, loss of intestinal peristalsis and decreased galactose uptake. All effects of PAF were abolished by the PAF-receptor antagonist ABT491 (2.5 μM). The COX and LOX inhibitors ASA and AA861 (500 μM, 10 μM) did not exhibit barrier-protective effects and the eicosanoid antagonists SQ29548 and MK571 (10 μM, each) only moderately attenuated the loss of vascular fluid, the redistribution to the lumen and the transfer of FITC dextran to the lumen. The steroid dexamethasone (10 μM) showed no barrier-protective properties and failed to prevent edema formation. Quinidine (100 μM) inhibited the increase in arterial pressure, stabilized all the intestinal barriers, and reduced lymph production and the transfer of FITC dextran to the lymph. While quinidine by itself reduced peristalsis, it also obviated paralysis, preserved intestinal functions and prevented edema formation. We conclude that quinidine exerts multiple protective effects against vasoconstriction, edema formation and paralysis in the intestine. The therapeutic use of quinidine for intestinal ailments

  18. Activation of toll like receptor-3 induces corneal epithelial barrier dysfunction.

    PubMed

    Wei, Jie; Jiang, Hua; Gao, Hongrui; Wang, Guangjie

    2015-06-01

    The epithelial barrier is critical in the maintenance of the homeostasis of the cornea. A number of eye disorders are associated with the corneal epithelial barrier dysfunction. Viral infection is one common eye disease type. This study aims to elucidate the mechanism by which the activation of toll like receptor 3 (TLR3) in the disruption of the corneal epithelial barrier. In this study, HCE cells (a human corneal epithelial cell line) were cultured into epithelial layers using as an in vitro model of the corneal epithelial barrier. PolyI:C was used as a ligand of TLR3. The transepithelial electric resistance (TER) and permeability of the HCE epithelial layer were assessed using as the parameters to evaluate the corneal epithelial barrier integrity. The results showed that exposure to PolyI:C markedly decreased the TER and increased the permeability of the HCE epithelial layers; the levels of cell junction protein, E-cadherin, were repressed by PolyI:C via increasing histone deacetylase-1 (HDAC1), the latter binding to the promoter of E-cadherin and repressed the transcription of E-cadherin. The addition of butyrate (an inhibitor of HDAC1) to the culture blocked the corneal epithelial barrier dysfunction caused by PolyI:C. In conclusion, activation of TLR3 can disrupt the corneal epithelial barrier, which can be blocked by the inhibitor of HDAC1. PMID:25912142

  19. Inhibitory effects of PPARγ ligands on TGF-β1-induced CTGF expression in cat corneal fibroblasts.

    PubMed

    Jeon, Kye-Im; Phipps, Richard P; Sime, Patricia J; Huxlin, Krystel R

    2015-09-01

    Ligands of Peroxisome Proliferator Activated Receptor gamma (PPARγ) possess strong anti-fibrotic properties in the cornea and several other body tissues. In the cornea, we recently showed this class of molecules to prevent stromal myofibroblast differentiation partially by blocking the actions of p38 mitogen-activated protein kinase (MAPK). However, given the important role assigned to connective tissue growth factor (CTGF) in mediating corneal fibrosis, here we asked whether PPARγ ligands also act by affecting transforming growth factor-β (TGF-β) 1-induced expression of CTGF in cultured corneal fibroblasts. Corneal keratocytes were isolated from young, adult cats and early passage cells were exposed to TGF-β1 with or without the PPARγ ligands Rosiglitazone, Troglitazone and 15d-PGJ2. Western blots were used to assay levels of CTGF and alpha smooth muscle actin (αSMA), a marker of myofibroblast differentiation. CTGF siRNA demonstrated a critical role for CTGF in TGF-β1-mediated myofibroblast differentiation, while exogenously applied CTGF potentiated the pro-fibrogenic effects of TGF-β1. TGF-β1-mediated increases in CTGF and αSMA expression were strongly inhibited by all three PPARγ ligands tested, and by a c-jun N-terminal kinase (JNK) inhibitor. However, while extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT) and p38 MAPK inhibitors also blocked TGF-β1-induced αSMA induction, they did not dampen TGF-β1-induced increases in levels of CTGF. Thus, we conclude that PPARγ ligands block TGF-β1-induced increases in CTGF levels in cat corneal fibroblasts. They appear to do this in addition to their anti-fibrotic effect on p38 MAPK, providing a second intracellular pathway by which PPARγ ligands block αSMA induction. PMID:26142957

  20. Inhibition of zymosan-induced cytokine and chemokine expression in human corneal fibroblasts by triptolide

    PubMed Central

    Liu, Yang; Li, Jing; Liu, Ye; Wang, Ping; Jia, Hui

    2016-01-01

    AIM To investigate the effects of triptolide on proinflammatory cytokine and chemokine expression induced by the fungal component zymosan in cultured human corneal fibroblasts (HCFs). METHODS HCFs were cultured in the absence or presence of zymosan or triptolide. The release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) into culture supernatants was measured with enzyme-linked immunosorbent assays. The cellular abundance of the mRNAs for these proteins was determined by reverse transcription and real-time polymerase chain reaction analysis. The phosphorylation of mitogen-activated protein kinases (MAPKs) and the endogenous nuclear factor-κB (NF-κB) inhibitor IκB-α was examined by immunoblot analysis. The release of lactate dehydrogenase (LDH) activity from HCFs was measured with a colorimetric assay. RESULTS Triptolide inhibited the zymosan-induced release of IL-6, IL-8, and MCP-1 from HCFs in a concentration- and time-dependent manner. It also inhibited the zymosan-induced up-regulation of IL-6, IL-8, and MCP-1 mRNA abundance in these cells. Furthermore, triptolide attenuated zymosan-induced phosphorylation of the MAPKs extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 as well as the phosphorylation and degradation of IκB-α. Triptolide did not exhibit cytotoxicity for HCFs. CONCLUSION Triptolide inhibited proinflammatory cytokine and chemokine production by HCFs exposed to zymosan, with this action likely being mediated by suppression of MAPK and NF-κB signaling pathways. This compound might thus be expected to limit the infiltration of inflammatory cells into the cornea associated with fungal infection. PMID:26949603

  1. Nab-paclitaxel-induced cystoid macular edema in a patient with pre-existing optic neuropathy.

    PubMed

    Park, Elizabeth; Goldberg, Naomi R; Adams, Sylvia

    2016-07-01

    Paclitaxel is a widely used chemotherapy agent that has rarely been associated with ophthalmic toxicities. Cystoid macular edema is one such rare side effect of paclitaxel therapy. Its pathophysiology remains poorly understood. Here, we report on a 69-year-old woman who developed cystoid macular edema associated with the albumin-bound formulation of paclitaxel after several months of therapy for breast cancer. After 2 months of drug withdrawal, her vision improved and there was a significant improvement in the macular edema by imaging with spectral-domain optical coherence tomography. Oncologists using taxane agents should be aware of this rare adverse outcome for timely patient referral to an ophthalmologist and appropriate treatment to preserve a patient's visual acuity. PMID:26982237

  2. Immune Modulation of B. terrestris Worker (a Type of Bumblebee), Extract on CFA-induced Paw Edema in Rats

    PubMed Central

    Kim, Soon Ja; Han, Jea Woong; Yoon, Hyung Joo; Hwang, Jae Sam; Yun, Eun Young

    2014-01-01

    To develop a composition for enhancing immunity, based on alcohol extracts of the bumblebee as an active ingredient, bumblebee ethanol extracts were evaluated for their protective effect in chronic models of inflammation, adjuvant induced rat arthritis. B. terrestris worker extract (SDIEX) and, B. hypocrita sapporoensis lava an pupa extract (SPDYBEX), significantly decreased paw edema in arthritic rats, at a dose 100 mg/kg, respectively. The cytokine levels related inflammation of COX-2, sPLA2, VEGF, and TNF-α, were decreased, compared to positive control, indomethacin (5 mg/kg). Histopathological data demonstrated decreases inflammatory activity, hind paw edema, and repaired hyaline articular cartilage in DRG over a 2 wk administration. HPLC and GC-MS analysis of SDIEX and SPDYBEX revealed the presence of cantharidin. PMID:25584147

  3. Spatiotemporally Regulated Ablation of Klf4 in Adult Mouse Corneal Epithelial Cells Results in Altered Epithelial Cell Identity and Disrupted Homeostasis

    PubMed Central

    Delp, Emili E.; Swamynathan, Sudha; Kao, Winston W.; Swamynathan, Shivalingappa K.

    2015-01-01

    Purpose. In previous studies, conditional disruption of Klf4 in the developing mouse ocular surface from embryonic day 10 resulted in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells, revealing the importance of Klf4 in ocular surface maturation. Here, we use spatiotemporally regulated ablation of Klf4 to investigate its functions in maintenance of adult corneal epithelial homeostasis. Methods. Expression of Cre was induced in ternary transgenic (Klf4LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre) mouse corneal epithelium by doxycycline administered through intraperitoneal injections and drinking water, to generate corneal epithelium–specific deletion of Klf4 (Klf4Δ/ΔCE). Corneal epithelial barrier function was tested by fluorescein staining. Expression of selected Klf4-target genes was determined by quantitative PCR (QPCR), immunoblotting, and immunofluorescent staining. Results. Klf4 was efficiently ablated within 5 days of doxycycline administration in adult Klf4Δ/ΔCE corneal epithelium. The Klf4Δ/ΔCE corneal epithelial barrier function was disrupted, and the basal cells were swollen and rounded after 15 days of doxycycline treatment. Increased numbers of cell layers and Ki67-positive proliferating cells suggested deregulated Klf4Δ/ΔCE corneal epithelial homeostasis. Expression of tight junction proteins ZO-1 and occludin, desmosomal Dsg and Dsp, basement membrane laminin-332, and corneal epithelial–specific keratin-12 was decreased, while that of matrix metalloproteinase Mmp9 and noncorneal keratin-17 increased, suggesting altered Klf4Δ/ΔCE corneal epithelial cell identity. Conclusions. Ablation of Klf4 in the adult mouse corneas resulted in the absence of characteristic corneal epithelial cell differentiation, disrupted barrier function, and squamous metaplasia, revealing that Klf4 is essential for maintenance of the adult corneal epithelial cell identity and homeostasis. PMID:26047041

  4. Corneal changes induced by laser ablation: study of the visual-quality evolution by a customized eye model

    NASA Astrophysics Data System (ADS)

    Ortiz, D.; Anera, R. G.; Saiz, J. M.; Jiménez, J. R.; Moreno, F.; Jiménez Del Barco, L.; González, F.

    2006-11-01

    This study focuses on the changes induced in both the asphericity and homogeneity of the cornea for a group of myopic eyes undergoing LASIK surgery. Eyes were characterized by a Kooijman-based customized eye model in which changes were introduced in the form of Gaussian-distributed refractive-index variations of given correlation length for the inhomogeneities and in the form of an expression, based on the modified Munnerlyn's paraxial formula, for the post-LASIK asphericity. Visual quality was evaluated in terms of the Modulation Transfer Function and the Point-Spread Function. The results show that, on average, the evolution of visual acuity is consistent with the change in corneal asphericity, while the evolution of contrast sensitivity requires a loss in corneal homogeneity in order to be explained. By including both effects in the model, the overall model performance in predicting visual quality is improved.

  5. Fuchs’ corneal dystrophy

    PubMed Central

    Eghrari, Allen O; Gottsch, John D

    2010-01-01

    Fuchs’ corneal dystrophy (FCD) is a progressive, hereditary disease of the cornea first described a century ago by the Austrian ophthalmologist Ernst Fuchs. Patients often present in the fifth to sixth decade of life with blurry morning vision that increases in duration as the disease progresses. Primarily a condition of the posterior cornea, characteristic features include the formation of focal excrescences of Descemet membrane termed ‘guttae’, loss of endothelial cell density and end-stage disease manifested by corneal edema and the formation of epithelial bullae. Recent advances in our understanding of the genetic and pathophysiological mechanisms of the disease, as well as the application of new imaging modalities and less invasive surgical procedures, present new opportunities for improved outcomes among patients with FCD. PMID:20625449

  6. Oxidative Stress Markers Induced by Hyperosmolarity in Primary Human Corneal Epithelial Cells

    PubMed Central

    Deng, Ruzhi; Hua, Xia; Li, Jin; Chi, Wei; Zhang, Zongduan; Lu, Fan; Zhang, Lili; Pflugfelder, Stephen C.; Li, De-Quan

    2015-01-01

    Oxidative stress has been known to be involved in pathogenesis of dry eye disease. However, few studies have comprehensively investigated the relationship between hyperosmolarity and oxidative damage in human ocular surface. This study was to explore whether and how hyperosmolarity induces oxidative stress markers in primary human corneal epithelial cells (HCECs). Primary HCECs were established from donor limbal explants. The hyperosmolarity model was made in HCECs cultured in isosmolar (312 mOsM) or hyperosmotic (350, 400, 450 mOsM) media. Production of reactive oxygen species (ROS), oxidative damage markers, oxygenases and anti-oxidative enzymes were analyzed by DCFDA kit, RT-qPCR, immunofluorescent and immunohistochemical staining and Western blotting. Compared to isosmolar medium, ROS production significantly increased at time- and osmolarity-dependent manner in HCECs exposed to media with increasing osmolarities (350–450 mOsM). Hyperosmolarity significantly induced oxidative damage markers in cell membrane with increased toxic products of lipid peroxidation, 4–hydroxynonenal (4-HNE) and malondialdehyde (MDA), and in nuclear and mitochondria DNA with increased aconitase-2 and 8-OHdG. Hyperosmotic stress also increased the mRNA expression and protein production of heme oxygenase-1 (HMOX1) and cyclooxygenase-2 (COX2), but reduced the levels of antioxidant enzymes, superoxide dismutase-1 (SOD1), and glutathione peroxidase-1 (GPX1). In conclusion, our comprehensive findings demonstrate that hyperosmolarity induces oxidative stress in HCECs by stimulating ROS production and disrupting the balance of oxygenases and antioxidant enzymes, which in turn cause cell damage with increased oxidative markers in membrane lipid peroxidation and mitochondrial DNA damage. PMID:26024535

  7. Hypoxia attenuates inflammatory mediators production induced by Acanthamoeba via Toll-like receptor 4 signaling in human corneal epithelial cells

    SciTech Connect

    Pan, Hong; Wu, Xinyi

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Hypoxia attenuates Acanthamoeba-induced the production of IL-8 and IFN-{beta}. Black-Right-Pointing-Pointer Hypoxia inhibits TLR4 expression in a time-dependent manner in HCECs. Black-Right-Pointing-Pointer Hypoxia inhibits Acanthamoeba-induced the activation of NF-{kappa}B and ERK1/2 in HCECs. Black-Right-Pointing-Pointer Hypoxia decreases Acanthamoeba-induced inflammatory response via TLR4 signaling. Black-Right-Pointing-Pointer LPS-induced the secretion of IL-6 and IL-8 is abated by hypoxia via TLR4 signaling. -- Abstract: Acanthamoeba keratitis (AK) is a vision-threatening corneal infection that is intimately associated with contact lens use which leads to hypoxic conditions on the corneal surface. However, the effect of hypoxia on the Acanthamoeba-induced host inflammatory response of corneal epithelial cells has not been studied. In the present study, we investigated the effect of hypoxia on the Acanthamoeba-induced production of inflammatory mediators interleukin-8 (IL-8) and interferon-{beta} (IFN-{beta}) in human corneal epithelial cells and then evaluated its effects on the Toll-like receptor 4 (TLR4) signaling, including TLR4 and myeloid differentiation primary response gene (88) (MyD88) expression as well as the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-{kappa}B) and extracellular signal-regulated kinases 1/2 (ERK1/2). We then studied the effect of hypoxia on a TLR4-specific inflammatory response triggered by the TLR4 ligand lipopolysaccharide (LPS). Our data showed that hypoxia significantly decreased the production of IL-8 and IFN-{beta}. Furthermore, hypoxia attenuated Acanthamoeba-triggered TLR4 expression as well as the activation of NF-{kappa}B and ERK1/2, indicating that hypoxia abated Acanthamoeba-induced inflammatory responses by affecting TLR4 signaling. Hypoxia also inhibited LPS-induced IL-6 and IL-8 secretion, myeloid differentiation primary response gene (88

  8. Bone marrow chimeras and c-fms conditional ablation (Mafia) mice reveal an essential role for resident myeloid cells in lipopolysaccharide/TLR4-induced corneal inflammation.

    PubMed

    Chinnery, Holly R; Carlson, Eric C; Sun, Yan; Lin, Michelle; Burnett, Sandra H; Perez, Victor L; McMenamin, Paul G; Pearlman, Eric

    2009-03-01

    The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4(-/-) mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)(+)/C57BL/6 or eGFP(+)/TLR4(-/-) mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4(-/-) mice reconstituted with C57BL/6, but not TLR4(-/-) bone marrow cells donor cells were found to cause infiltration of eGFP(+) cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP(+) cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1alpha production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation. PMID:19234168

  9. Bone Marrow Chimeras and c-fms Conditional Ablation (Mafia) Mice Reveal an Essential Role for Resident Myeloid Cells in Lipopolysaccharide/TLR4-Induced Corneal Inflammation1

    PubMed Central

    Chinnery, Holly R.; Carlson, Eric C.; Sun, Yan; Lin, Michelle; Burnett, Sandra H.; Perez, Victor L.; McMenamin, Paul G.; Pearlman, Eric

    2012-01-01

    The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4−/− mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)+/C57BL/6 or eGFP+/TLR4−/− mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4−/− mice reconstituted with C57BL/6, but not TLR4−/− bone marrow cells donor cells were found to cause infiltration of eGFP+ cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP+ cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1α production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation. PMID:19234168

  10. Evidence for a role of mast cells in the lung edema induced by Tityus serrulatus venom in rats.

    PubMed

    De-Matos, I M; Talvani, A; Rocha, O O; Freire-Maia, L; Teixeira, M M

    2001-06-01

    In the most severe cases of human poisoning by Tityus serrulatus, pulmonary edema is a frequent finding and can be the cause of death. Mast cells can release a range of mediators known to be involved in the development of lung edema following T. serrulatus venom injection. The present work was designed to investigate whether mast cells participated in the acute lung injury induced by T. serrulatus scorpion venom and could, thus, be an intermediate between neuropeptide release and activation of the inflammatory cascade. To this end, mast cells were depleted using compound 48/80. Pulmonary edema, as assessed by the levels of extravasation of Evans blue dye in the bronchoalveolar lavage and in the left lung, was completely inhibited in compound 48/80-treated animals. Moreover, the number of animals surviving 60min after injection of venom rose from 20 to 60%. Our results demonstrate an important role for mast cells in the development of lung injury and lethality following the intravenous administration of T. serrulatus venom. PMID:11137547

  11. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice.

    PubMed

    Huh, Dongeun; Leslie, Daniel C; Matthews, Benjamin D; Fraser, Jacob P; Jurek, Samuel; Hamilton, Geraldine A; Thorneloe, Kevin S; McAlexander, Michael Allen; Ingber, Donald E

    2012-11-01

    Preclinical drug development studies currently rely on costly and time-consuming animal testing because existing cell culture models fail to recapitulate complex, organ-level disease processes in humans. We provide the proof of principle for using a biomimetic microdevice that reconstitutes organ-level lung functions to create a human disease model-on-a-chip that mimics pulmonary edema. The microfluidic device, which reconstitutes the alveolar-capillary interface of the human lung, consists of channels lined by closely apposed layers of human pulmonary epithelial and endothelial cells that experience air and fluid flow, as well as cyclic mechanical strain to mimic normal breathing motions. This device was used to reproduce drug toxicity-induced pulmonary edema observed in human cancer patients treated with interleukin-2 (IL-2) at similar doses and over the same time frame. Studies using this on-chip disease model revealed that mechanical forces associated with physiological breathing motions play a crucial role in the development of increased vascular leakage that leads to pulmonary edema, and that circulating immune cells are not required for the development of this disease. These studies also led to identification of potential new therapeutics, including angiopoietin-1 (Ang-1) and a new transient receptor potential vanilloid 4 (TRPV4) ion channel inhibitor (GSK2193874), which might prevent this life-threatening toxicity of IL-2 in the future. PMID:23136042

  12. Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity

    PubMed Central

    Hirata, Harumitsu; Mizerska, Kamila; Marfurt, Carl F.; Rosenblatt, Mark I.

    2015-01-01

    Purpose In an effort to elucidate possible neural mechanisms underlying diminished tearing in dry eye disease, this study sought to determine if hyperosmolar tears, a ubiquitous sign of dry eye disease, produce functional changes in corneal nerve responses to drying of the cornea and if these changes correlate with alterations in corneal nerve morphology. Methods In vivo extracellular electrophysiological recordings were performed in rat trigeminal ganglion neurons that innervated the cornea before, and up to 3 hours after, the ocular application of continuous hyperosmolar tears or artificial tears. In corollary experiments, immunohistochemical staining was performed to compare corneal nerve morphology in control and in eyes treated with hyperosmolar solutions. Results Our previous studies identified a population of corneal afferents, dry-sensitive neurons that are strongly excited by corneal dessication (“dry response”), a response thought to trigger the lacrimation reflex. In the present study, we found that the dry responses of corneal dry-sensitive neurons were depressed or even completely abolished by hyperosmolar tears in a time- (30 minutes to 3 hours) and dose (450- to 1000-mOsm solutions)-dependent manner. Furthermore, eyes treated with hyperosmolar tears for 3 hours contained large numbers of morphologically abnormal (granular, fragmented, or prominently beaded) subbasal nerves that appeared to be undergoing degeneration. Conclusions These results demonstrate that tear hyperosmolarity, considered to be a “core” mechanism of dry eye disease, significantly decreases physiological sensitivity and morphologic integrity of the corneal nerves important in tear production. These alterations might contribute to the diminished tearing seen clinically in dry eye patients. PMID:26720465

  13. A comparative study of corneal incisions induced by diamond and steel knives and two ultraviolet radiations from an excimer laser.

    PubMed Central

    Marshall, J; Trokel, S; Rothery, S; Krueger, R R

    1986-01-01

    This paper reviews the potential role of excimer lasers in corneal surgery. The morphology of incisions induced by two wavelengths of excimer laser radiation, 193 nm and 248 nm, are compared with the morphology of incisions produced by diamond and steel knives. Analysis suggests that ablation induced by excimer laser results from highly localised photochemical reactions and that 193 nm is the optimal wavelength for surgery. The only significant complication of laser surgery is loss of endothelial cells when incisions are within 40 micron of Descemet's membrane. Images PMID:3013283

  14. Treadmill exercise ameliorates ischemia-induced brain edema while suppressing Na⁺/H⁺ exchanger 1 expression.

    PubMed

    Nishioka, Ryutaro; Sugimoto, Kana; Aono, Hitomi; Mise, Ayano; Choudhury, Mohammed E; Miyanishi, Kazuya; Islam, Afsana; Fujita, Takahiro; Takeda, Haruna; Takahashi, Hisaaki; Yano, Hajime; Tanaka, Junya

    2016-03-01

    Exercise may be one of the most effective and sound therapies for stroke; however, the mechanisms underlying the curative effects remain unclear. In this study, the effects of forced treadmill exercise with electric shock on ischemic brain edema were investigated. Wistar rats were subjected to transient (90 min) middle cerebral artery occlusion (tMCAO). Eighty nine rats with substantially large ischemic lesions were evaluated using magnetic resonance imaging (MRI) and were randomly assigned to exercise and non-exercise groups. The rats were forced to run at 4-6m/s for 10 min/day on days 2, 3 and 4. Brain edema was measured on day 5 by MRI, histochemical staining of brain sections and tissue water content determination (n=7, each experiment). Motor function in some rats was examined on day 30 (n=6). Exercise reduced brain edema (P<0.05-0.001, varied by the methods) and ameliorated motor function (P<0.05). The anti-glucocorticoid mifepristone or the anti-mineralocorticoid spironolactone abolished these effects, but orally administered corticosterone mimicked the ameliorating effects of exercise. Exercise prevented the ischemia-induced expression of mRNA encoding aquaporin 4 (AQP4) and Na(+)/H(+) exchangers (NHEs) (n=5 or 7, P<0.01). Microglia and NG2 glia expressed NHE1 in the peri-ischemic region of rat brains and also in mixed glial cultures. Corticosterone at ~10nM reduced NHE1 and AQP4 expression in mixed glial and pure microglial cultures. Dexamethasone and aldosterone at 10nM did not significantly alter NHE1 and AQP4 expression. Exposure to a NHE inhibitor caused shrinkage of microglial cells. These results suggest that the stressful short-period and slow-paced treadmill exercise suppressed NHE1 and AQP4 expression resulting in the amelioration of brain edema at least partly via the moderate increase in plasma corticosterone levels. PMID:26724742

  15. Pulmonary Edema

    PubMed Central

    Tanser, Paul H.

    1980-01-01

    The physician who deals with pulmonary edema from a pathophysiologic basis will seldom make a diagnostic or therapeutic error. Recent additions to preload and afterload therapy have greatly helped in the emergency and ambulatory treatment of pulmonary edema due to left heart failure. Careful follow-up and patient self-monitoring are the most effective means of reducing hospitalization of chronic heart failure patients. PMID:21293700

  16. Long-term Outcomes of Amniotic Membrane Transplantation in Contact Lens-Induced Pseudomonas Keratitis with Impending Corneal Perforation

    PubMed Central

    Mohammadpour, Mehrdad; Sabet, Fatemeh Alsadat

    2016-01-01

    Purpose: To report the anatomical and visual outcomes of double layered amniotic membrane transplantation (AMT) in eyes with advanced Pseudomonas keratitis leading to Descemetocele formation. Methods: This prospective interventional case series included 6 eyes of 6 female patients with pseudomonas keratitis caused by contact lens-induced infection who underwent double layered AMT. Surgery was performed after the ulcers were found to be poorly responsive to antibiotics, and severe thinning or Descemetocele had developed. All patients underwent a complete examination pre- and postoperatively, as well as anterior segment optical coherence tomography (OCT) and pachymetry or Orbscan after the procedure. Results: Mean follow-up period was 24 months. There was neither frank corneal perforation nor a need for emergent corneal transplantation in any of the eyes. All patients had visual acuity of hand motions before the procedure which improved to 20/50 to 20/30 three months after surgery. No surgical or postoperative complication occurred in this series. Conclusion: Double layered AMT may result in acceptable anatomical outcomes in patients with advanced Pseudomonas keratitis with Descemetocele formation and can eliminate the need for emergent corneal transplantation. PMID:27195083

  17. In vitro ultraviolet–induced damage in human corneal, lens, and retinal pigment epithelial cells

    PubMed Central

    Youn, Hyun-Yi; Sivak, Jacob G.; Jones, Lyndon W.

    2011-01-01

    Purpose The purpose was to develop suitable in vitro methods to detect ocular epithelial cell damage when exposed to UV radiation, in an effort to evaluate UV-absorbing ophthalmic biomaterials. Methods Human corneal epithelial cells (HCEC), lens epithelial cells (HLEC), and retinal pigment epithelial cells (ARPE-19) were cultured and Ultraviolet A/Ultraviolet B (UVA/UVB) blocking filters and UVB-only blocking filters were placed between the cells and a UV light source. Cells were irradiated with UV radiations at various energy levels with and without filter protections. Cell viability after exposure was determined using the metabolic dye alamarBlue and by evaluating for changes in the nuclei, mitochondria, membrane permeability, and cell membranes of the cells using the fluorescent dyes Hoechst 33342, rhodamine 123, calcein AM, ethidium homodimer-1, and annexin V. High-resolution images of the cells were taken with a Zeiss 510 confocal laser scanning microscope. Results The alamarBlue assay results of UV-exposed cells without filters showed energy level-dependent decreases in cellular viability. However, UV treated cells with 400 nm LP filter protection showed the equivalent viability to untreated control cells at all energy levels. Also, UV irradiated cells with 320 nm LP filter showed lower cell viability than the unexposed control cells, yet higher viability than UV-exposed cells without filters in an energy level-dependent manner. The confocal microscopy results also showed that UV radiation can cause significant dose-dependent degradations of nuclei and mitochondria in ocular cells. The annexin V staining also showed an increased number of apoptotic cells after UV irradiation. Conclusions The findings suggest that UV-induced HCEC, HLEC, and ARPE-19 cell damage can be evaluated by bioassays that measure changes in the cell nuclei, mitochondria, cell membranes, and cell metabolism, and these assay methods provide a valuable in vitro model for evaluating the

  18. Aqueous and Methanolic Extracts of Caulerpa mexicana Suppress Cell Migration and Ear Edema Induced by Inflammatory Agents

    PubMed Central

    Bitencourt, Mariana Angelica Oliveira; Dantas, Gracielle Rodrigues; Lira, Daysianne Pereira; Barbosa-Filho, Jose Maria; de Miranda, George Emmanuel Cavalcanti; de Oliveira Santos, Barbara Viviana; Souto, Janeusa Trindade

    2011-01-01

    The regulation of the inflammatory response is essential to maintaining homeostasis. Several studies have investigated new drugs that may contribute to avoiding or minimizing excessive inflammatory process. The aim of this study was to evaluate the effect of extracts of green algae Caulerpa mexicana on models inflammation. In mice, the inflammatory peritonitis model is induced by zymosan. Previous treatment of mice with aqueous and methanolic extracts of C. mexicana was able to suppress the cell migration to the peritoneal cavity, in a time-dependent but not in a dose-dependent manner. The treatment of mice with C. mexicana extracts also decreased the xylene-induced ear edema, exerting strong inhibitory leukocyte migration elicited by zymosan into the air pouch. We concluded that administration of the extracts resulted in a reduction of cell migration to different sites as well as a decrease in edema formation induced by chemical irritants. This study demonstrates for the first time the anti-inflammatory effect of aqueous and methanolic extracts from the green marine algae Caulerpa mexicana. PMID:21892348

  19. Novel Peptide for Attenuation of Hyperoxia-induced Disruption of Lung Endothelial Barrier and Pulmonary Edema via Modulating Peroxynitrite Formation*

    PubMed Central

    Kondrikov, Dmitry; Gross, Christine; Black, Stephen M.; Su, Yunchao

    2014-01-01

    Pulmonary damages of oxygen toxicity include vascular leakage and pulmonary edema. We have previously reported that hyperoxia increases the formation of NO and peroxynitrite in lung endothelial cells via increased interaction of endothelial nitric oxide (eNOS) with β-actin. A peptide (P326TAT) with amino acid sequence corresponding to the actin binding region of eNOS residues 326–333 has been shown to reduce the hyperoxia-induced formation of NO and peroxynitrite in lung endothelial cells. In the present study, we found that exposure of pulmonary artery endothelial cells to hyperoxia (95% oxygen and 5% CO2) for 48 h resulted in disruption of monolayer barrier integrity in two phases, and apoptosis occurred in the second phase. NOS inhibitor NG-nitro-l-arginine methyl ester attenuated the endothelial barrier disruption in both phases. Peroxynitrite scavenger uric acid did not affect the first phase but ameliorated the second phase of endothelial barrier disruption and apoptosis. P326TAT inhibited hyperoxia-induced disruption of monolayer barrier integrity in two phases and apoptosis in the second phase. More importantly, injection of P326TAT attenuated vascular leakage, pulmonary edema, and endothelial apoptosis in the lungs of mice exposed to hyperoxia. P326TAT also significantly reduced the increase in eNOS-β-actin association and protein tyrosine nitration. Together, these results indicate that peptide P326TAT ameliorates barrier dysfunction of hyperoxic lung endothelial monolayer and attenuates eNOS-β-actin association, peroxynitrite formation, endothelial apoptosis, and pulmonary edema in lungs of hyperoxic mice. P326TAT can be a novel therapeutic agent to treat or prevent acute lung injury in oxygen toxicity. PMID:25315770

  20. Brm Inhibits the Proliferative Response of Keratinocytes and Corneal Epithelial Cells to Ultraviolet Radiation-Induced Damage

    PubMed Central

    Hassan, Nur Mohammad Monsur; Painter, Nicole; Howlett, C. Rolfe; Farrell, Andrew W.; Di Girolamo, Nick; Lyons, J. Guy; Halliday, Gary M.

    2014-01-01

    Ultraviolet radiation (UV) from sunlight is the primary cause of skin and ocular neoplasia. Brahma (BRM) is part of the SWI/SNF chromatin remodeling complex. It provides energy for rearrangement of chromatin structure. Previously we have found that human skin tumours have a hotspot mutation in BRM and that protein levels are substantially reduced. Brm−/− mice have enhanced susceptibility to photocarcinogenesis. In these experiments, Brm−/− mice, with both or a single Trp53 allele were exposed to UV for 2 or 25 weeks. In wild type mice the central cornea and stroma became atrophic with increasing time of exposure while the peripheral regions became hyperplastic, presumably as a reparative process. Brm−/−, Trp53+/−, and particularly the Brm−/− Trp53+/− mice had an exaggerated hyperplastic regeneration response in the corneal epithelium and stroma so that the central epithelial atrophy or stromal loss was reduced. UV induced hyperplasia of the epidermis and corneal epithelium, with an increase in the number of dividing cells as determined by Ki-67 expression. This response was considerably greater in both the Brm−/− Trp53+/+ and Brm−/− Trp53+/− mice indicating that Brm protects from UV-induced enhancement of cell division, even with loss of one Trp53 allele. Cell division was disorganized in Brm−/− mice. Rather than being restricted to the basement membrane region, dividing cells were also present in the suprabasal regions of both tissues. Brm appears to be a tumour suppressor gene that protects from skin and ocular photocarcinogenesis. These studies indicate that Brm protects from UV-induced hyperplastic growth in both cutaneous and corneal keratinocytes, which may contribute to the ability of Brm to protect from photocarcinogenesis. PMID:25254962

  1. microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration.

    PubMed

    Wang, Ye; Zhao, Xiaowen; Wu, Xiaoming; Dai, Yunhai; Chen, Peng; Xie, Lixin

    2016-07-01

    Sensory neurons are particularly susceptible to neuronal damage in diabetes, and silent mating type information regulation 2 homolog 1 (Sirt1) has been recently identified as a key gene in neuroprotection and wound healing. We found that the expression of Sirt1 was downregulated in trigeminal sensory neurons of diabetic mice. A microRNA microarray analysis identified microRNA-182 (miR-182) as a Sirt1 downstream effector, and the expression level of miR-182 was increased by Sirt1 overexpression in trigeminal neurons; Sirt1 bound to the promoter of miR-182 and regulated its transcription. We also revealed that miR-182 enhanced neurite outgrowth in isolated trigeminal sensory neurons and overcame the detrimental effects of hyperglycemia by stimulating corneal nerve regeneration by decreasing the expression of one of its target genes, NOX4. Furthermore, the effects of miR-182 on corneal nerve regeneration are associated with a functional recovery of corneal sensation in hyperglycemic conditions. These data demonstrate that miR-182 is a key regulator in diabetic corneal nerve regeneration through targeting NOX4, suggesting that miR-182 might be a potential target for the treatment of diabetic sensory nerve regeneration and diabetic keratopathy. PMID:27207535

  2. Keratin 12 missense mutation induces the unfolded protein response and apoptosis in Meesmann epithelial corneal dystrophy

    PubMed Central

    Allen, Edwin H.A.; Courtney, David G.; Atkinson, Sarah D.; Moore, Johnny E.; Mairs, Laura; Poulsen, Ebbe Toftgaard; Schiroli, Davide; Maurizi, Eleonora; Cole, Christian; Hickerson, Robyn P.; James, John; Murgatroyd, Helen; Smith, Frances J.D.; MacEwen, Carrie; Enghild, Jan J.; Nesbit, M. Andrew; Leslie Pedrioli, Deena M.; McLean, W.H. Irwin; Moore, C.B. Tara

    2016-01-01

    Meesmann epithelial corneal dystrophy (MECD) is a rare autosomal dominant disorder caused by dominant-negative mutations within the KRT3 or KRT12 genes, which encode the cytoskeletal protein keratins K3 and K12, respectively. To investigate the pathomechanism of this disease, we generated and phenotypically characterized a novel knock-in humanized mouse model carrying the severe, MECD-associated, K12-Leu132Pro mutation. Although no overt changes in corneal opacity were detected by slit-lamp examination, the corneas of homozygous mutant mice exhibited histological and ultrastructural epithelial cell fragility phenotypes. An altered keratin expression profile was observed in the cornea of mutant mice, confirmed by western blot, RNA-seq and quantitative real-time polymerase chain reaction. Mass spectrometry (MS) and immunohistochemistry demonstrated a similarly altered keratin profile in corneal tissue from a K12-Leu132Pro MECD patient. The K12-Leu132Pro mutation results in cytoplasmic keratin aggregates. RNA-seq analysis revealed increased chaperone gene expression, and apoptotic unfolded protein response (UPR) markers, CHOP and Caspase 12, were also increased in the MECD mice. Corneal epithelial cell apoptosis was increased 17-fold in the mutant cornea, compared with the wild-type (P < 0.001). This elevation of UPR marker expression was also observed in the human MECD cornea. This is the first reporting of a mouse model for MECD that recapitulates the human disease and is a valuable resource in understanding the pathomechanism of the disease. Although the most severe phenotype is observed in the homozygous mice, this model will still provide a test-bed for therapies not only for corneal dystrophies but also for other keratinopathies caused by similar mutations. PMID:26758872

  3. Corneal Alternations Induced by Topical Application of Benzalkonium Chloride in Rabbit

    PubMed Central

    Chen, Wensheng; Li, Zhiyuan; Hu, Jiaoyue; Zhang, Zhenhao; Chen, Lelei; Chen, Yongxiong; Liu, Zuguo

    2011-01-01

    Benzalkonium chloride (BAC) is the most common preservative in ophthalmic preparations. Here, we investigated the corneal alternations in rabbits following exposure to BAC. Twenty-four adult male New Zealand albino rabbits were randomly divided into three groups. BAC at 0.01%, 0.05%, or 0.1% was applied twice daily to one eye each of rabbits for 4 days. The contralateral untreated eyes were used as control. Aqueous tear production and fluorescein staining scores of BAC-treated eyes were compared with those of controls. The structure of the central cornea was examined by in vivo confocal microscopy. Expression of mucin-5 subtype AC (MUC5AC) in conjunctiva was detected by immunostainig on cryosections. Corneal barrier function was assessed in terms of permeability to carboxy fluorescein (CF). The distribution and expression of ZO-1, a known marker of tight junction, and reorganization of the perijunctional actomyosin ring (PAMR) were examined by immunofluorescence analysis. Although there were no significant differences between control and BAC-treated eyes in Schirmer scores, corneal fluorescein scores and the number of conjunctival MUC5AC staining cells, in vivo confocal microscopy revealed significant epithelial and stromal defects in all BAC-treated corneas. Moreover, BAC at 0.1% resulted in significant increases in central corneal thickness and endothelial CF permeability, compared with those in control eyes, and endothelial cell damage with dislocation of ZO-1 and disruption of PAMR. Topical application of BAC can quickly impair the whole cornea without occurrence of dry eye. A high concentration of BAC breaks down the barrier integrity of corneal endothelium, concomitant with the disruption of PAMR and remodeling of apical junctional complex in vivo. PMID:22022526

  4. Mechanisms involved in the protection of UV-induced protein inactivation by the corneal crystallin ALDH3A1.

    PubMed

    Estey, Tia; Cantore, Miriam; Weston, Philip A; Carpenter, John F; Petrash, J Mark; Vasiliou, Vasilis

    2007-02-16

    Various lines of evidence have shown that ALDH3A1 (aldehyde dehydrogenase 3A1) plays a critical and multifaceted role in protecting the cornea from UV-induced oxidative stress. ALDH3A1 is a corneal crystallin, which is defined as a protein recruited into the cornea for structural purposes without losing its primary function (i.e. metabolism). Although the primary role of ALDH3A1 in the metabolism of toxic aldehydes has been clearly demonstrated, including the detoxification of aldehydes produced during UV-induced lipid peroxidation, the structural role of ALDH3A1 in the cornea remains elusive. We therefore examined the potential contribution of ALDH3A1 in maintaining the optical integrity of the cornea by suppressing the aggregation and/or inactivation of other proteins through chaperone-like activity and other protective mechanisms. We found that ALDH3A1 underwent a structural transition near physiological temperatures to form a partially unfolded conformation that is suggestive of chaperone activity. Although this structural transition alone did not correlate with any protection, ALDH3A1 substantially reduced the inactivation of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal and malondialdehyde when co-incubated with NADP(+), reinforcing the importance of the metabolic function of this corneal enzyme in the detoxification of toxic aldehydes. A large excess of ALDH3A1 also protected glucose-6-phosphate dehydrogenase from inactivation because of direct exposure to UVB light, which suggests that ALDH3A1 may shield other proteins from damaging UV rays. Collectively, these data demonstrate that ALDH3A1 can reduce protein inactivation and/or aggregation not only by detoxification of reactive aldehydes but also by directly absorbing UV energy. This study provides for the first time mechanistic evidence supporting the structural role of the corneal crystallin ALDH3A1 as a UV-absorbing constituent of the cornea. PMID:17158879

  5. Blue light-induced retinal lesions, intraretinal vascular leakage and edema formation in the all-cone mouse retina

    PubMed Central

    Geiger, P; Barben, M; Grimm, C; Samardzija, M

    2015-01-01

    Little is known about the mechanisms underlying macular degenerations, mainly for the scarcity of adequate experimental models to investigate cone cell death. Recently, we generated R91W;Nrl−/− double-mutant mice, which display a well-ordered all-cone retina with normal retinal vasculature and a strong photopic function that generates useful vision. Here we exposed R91W;Nrl−/− and wild-type (wt) mice to toxic levels of blue light and analyzed their retinas at different time points post illumination (up to 10 days). While exposure of wt mice resulted in massive pyknosis in a focal region of the outer nuclear layer (ONL), the exposure of R91W;Nrl−/− mice led to additional cell death detected within the inner nuclear layer. Microglia/macrophage infiltration at the site of injury was more pronounced in the all-cone retina of R91W;Nrl−/− than in wt mice. Similarly, vascular leakage was abundant in the inner and outer retina in R91W;Nrl−/− mice, whereas it was mild and restricted to the subretinal space in wt mice. This was accompanied by retinal swelling and the appearance of cystoid spaces in both inner and ONLs of R91W;Nrl−/− mice indicating edema in affected areas. In addition, basal expression levels of tight junction protein-1 encoding ZO1 were lower in R91W;Nrl−/− than in wt retinas. Collectively, our data suggest that exposure of R91W;Nrl−/− mice to blue light not only induces cone cell death but also disrupts the inner blood–retinal barrier. Macular edema in humans is a result of diffuse capillary leakage and microaneurysms in the macular region. Blue light exposure of the R91W;Nrl−/− mouse could therefore be used to study molecular events preceding edema formation in a cone-rich environment, and thus potentially help to develop treatment strategies for edema-based complications in macular degenerations. PMID:26583326

  6. Corneal injury

    MedlinePlus

    ... as sand or dust Ultraviolet injuries: Caused by sunlight, sun lamps, snow or water reflections, or arc- ... a corneal injury if you: Are exposed to sunlight or artificial ultraviolet light for long periods of ...

  7. Corneal transplant

    MedlinePlus

    ... clear outer lens on the front of the eye. A corneal transplant is surgery to replace the cornea with tissue ... years. Rejection can sometimes be controlled with steroid eye drops. Other ... are: Bleeding Cataracts Infection of the eye Glaucoma ( ...

  8. Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

    PubMed

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative. PMID:25215245

  9. Nicardipine-Induced Acute Pulmonary Edema: A Rare but Severe Complication of Tocolysis

    PubMed Central

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative. PMID:25215245

  10. Observation on ultrastructure and histopathology of cornea following femtosecond laser-assisted deep lamellar keratoplasty for acute corneal alkaline burns

    PubMed Central

    Li, Wen-Jing; Hu, Yu-Kun; Song, Hui; Gao, Xiao-Wei; Zhao, Xu-Dong; Dong, Jing; Guo, Yun-Lin; Cai, Yan

    2016-01-01

    AIM To demonstrate the changes in ultrastructure and histopathology of the cornea in acute corneal alkaline burns after femtosecond laser-assisted deep lamellar keratoplasty. METHODS The New Zealand white rabbits treated with alkaline corneal burn were randomized into two groups, Group A (16 eyes) with femtosecond laser-assisted deep lamellar keratoplasty 24h after burn and Group B (16 eyes) without keratoplasty as controls. All eyes were evaluated with transmission electron microscopy (TEM) at 1, 2, 3, and 4wk follow-up, then all corneas were tested by hematoxylin and eosin staining histology. RESULTS The corneal grafts in Group A were transparent, while those in Group B showed corneal stromal edema and loosely arranged collagen fibers. One week after treatment, TEM revealed the intercellular desmosomes in the epithelial layers and intact non-dissolving nuclei in Group A. At week 4, the center of the corneas in Group A was transparent with regularly arranged collagen fibers and fibroblasts in the stroma. In Group B, squamous cells were observed on the corneal surface and some epithelial cells were detached. CONCLUSION Femtosecond laser-assisted deep lamellar keratoplasty can suppress inflammatory responses, prevent toxic substance-induced injury to the corneal endothelium and inner tissues with quicker recovery and better visual outcomes. PMID:27162716

  11. Vortex or whorl formation of cultured human corneal epithelial cells induced by magnetic fields.

    PubMed

    Dua, H S; Singh, A; Gomes, J A; Laibson, P R; Donoso, L A; Tyagi, S

    1996-01-01

    The terms 'vortex keratopathy' and 'hurricane keratopathy' describe two similar conditions affecting the corneal surface. In the former, a vortex or whorl pattern is seen on the corneal surface and is due to the deposition of substances such as pigment, iron or drugs in the epithelial cells. In the latter, a similar pattern is presented by migrating epithelial cells but, unlike the former, the pattern is rendered more visible by fluorescein staining. Both represent the migratory pattern of normal epithelial cells which is otherwise not visible due to the slow rate of epithelial turnover and migration. The whorl pattern has a clockwise predisposition in the majority of cases and is hypothesised to be due to the influence of ocular electro-magnetic fields on the migrating epithelial cells. In this study we tested in vitro the effect of static magnetic fields on corneal epithelial cells. We were able to reproduce dramatic vortex or whorl patterns in response to magnetic fields, but without preferential migration towards the North or South Pole. PMID:8944095

  12. Advances in corneal cell therapy.

    PubMed

    Fuest, Matthias; Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Mehta, Jodhbir S

    2016-09-01

    Corneal integrity is essential for visual function. Transplantation remains the most common treatment option for advanced corneal diseases. A global donor material shortage requires a search for alternative treatments. Different stem cell populations have been induced to express corneal cell characteristics in vitro and in animal models. Yet before their application to humans, scientific and ethical issues need to be solved. The in vitro propagation and implantation of primary corneal cells has been rapidly evolving with clinical practices of limbal epithelium transplantation and a clinical trial for endothelial cells in progress, implying cultivated ocular cells as a promising option for the future. This review reports on the latest developments in primary ocular cell and stem cell research for corneal therapy. PMID:27498943

  13. Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes.

    PubMed

    Mallet, Justin D; Dorr, Marie M; Drigeard Desgarnier, Marie-Catherine; Bastien, Nathalie; Gendron, Sébastien P; Rochette, Patrick J

    2016-01-01

    Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced. PMID:27611318

  14. Halofuginone down-regulates Smad3 expression and inhibits the TGFbeta-induced expression of fibrotic markers in human corneal fibroblasts

    PubMed Central

    Nelson, Elizabeth F.; Huang, Craig W.; Ewel, Jillian M.; Chang, Angela A.

    2012-01-01

    Purpose Due to its ability to disrupt transforming growth factor beta (TGF-β) signaling, halofuginone has been successfully used to treat various fibrotic disorders. Here we investigated the antifibrotic potential of halofuginone in human corneal fibroblasts. Methods Human corneal fibroblasts were isolated from human donor corneas for in vitro experiments. TGF-β was used to stimulate pro-fibrotic responses from corneal fibroblasts under halofuginone treatment. The expression of alpha smooth muscle actin (α-SMA) and fibronectin was analyzed by western blots. Phalloidin toxin was used to stain cultures for stress fiber assemblies. Quantitative reverse transcription PCR (qRT–PCR) and immunostaining were used to analyze the expression of type I collagen mRNA and protein, respectively. The expression of Smad2, Smad3, phospho-Smad2, and phospho-Smad3 was determined by western blots. Results Halofuginone was well tolerated by human corneal fibroblasts up to 10 ng/ml as demonstrated by a cell viability assay. At this concentration, TGF-β-induced expression of the fibrotic markers α-SMA, fibronectin, and type I collagen was significantly reduced. Interestingly, under our experimental conditions, halofuginone treatment led to reduced protein expression of Smad3, which was both dose- and time-dependent. Conclusions Our results suggest that halofuginone may exert its antifibrotic effects in the cornea via a novel molecular mechanism and may be used as an antifibrotic agent for corneal fibrosis treatment. PMID:22393274

  15. The anti-inflammatory effects of venlafaxine in the rat model of carrageenan-induced paw edema

    PubMed Central

    Hajhashemi, Valiollah; Minaiyan, Mohsen; Banafshe, Hamid Reza; Mesdaghinia, Azam; Abed, Alireza

    2015-01-01

    Objective(s): Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin norepinephrine reuptake inhibition property. The pain alleviating properties of venlafaxine in different pain models such as neurogenic pain, diabetic neuropathy, and fibromyalgia have been demonstrated. Anti-inflammatory effects of venlafaxine and also its underlying mechanisms remain unclear. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine and determine possible underlying mechanisms. Materials and Methods: We examined the anti-inflammatory effects of intraperitoneal (IP) and intracerebroventricular (ICV) administration of venlafaxine in the rat model of carrageenan-induced paw edema. Results: Our results showed that both IP (50 and 100 mg/kg) and ICV (50 and 100 μg/rat) injection of venlafaxine inhibited carrageenan-induced paw edema. Also IP and ICV administration of venlafaxine significantly decreased myeloperoxidase (MPO) activity and interleukin (IL)-1β and tumor necrosis factor (TNF)-α production. Finally, we tried to reverse the anti-inflammatory effect of venlafaxine by yohimbine (5 mg/kg, IP), an alpha2-adrenergic antagonist. Our results showed that applied antagonist failed to change the anti-inflammatory effect of venlafaxine. Conclusion: These results demonstrated that venlafaxine has potent anti-inflammatory effect which is related to the peripheral and central effects of this drug. Also we have shown that anti-inflammatory effect of venlafaxine is mediated mostly through the inhibition of IL-1β and TNF-α production and decreases MPO activity in the site of inflammation. PMID:26351555

  16. Micromechanics of alveolar edema.

    PubMed

    Perlman, Carrie E; Lederer, David J; Bhattacharya, Jahar

    2011-01-01

    The decrease of lung compliance in pulmonary edema underlies ventilator-induced lung injury. However, the cause of the decrease in compliance is unknown. We tested the hypothesis that in pulmonary edema, the mechanical effects of liquid-filled alveoli increase tissue stress in adjacent air-filled alveoli. By micropuncture of isolated, perfused rat lungs, we established a single-alveolus model of pulmonary edema that we imaged using confocal microscopy. In this model, we viewed a liquid-filled alveolus together with its air-filled neighbor at different transpulmonary pressures, both before and after liquid-filling. Instilling liquid in an alveolus caused alveolar shrinkage. As a result, the interalveolar septum was stretched, causing the neighboring air-filled alveolus to bulge. Thus, the air-filled alveolus was overexpanded by virtue of its adjacency to a liquid-filled alveolus. Confocal microscopy at different depths of the liquid-filled alveolus revealed a meniscus. Lung inflation to near-total lung capacity (TLC) demonstrated decreased compliance of the air-filled but not liquid-filled alveolus. However, at near TLC, the air-filled alveolus was larger than it was in the pre-edematous control tissue. In pulmonary edema, liquid-filled alveoli induce mechanical stress on air-filled alveoli, reducing the compliance of air-filled alveoli, and hence overall lung compliance. Because of increased mechanical stress, air-filled alveoli may be susceptible to overdistension injury during mechanical ventilation of the edematous lung. PMID:20118224

  17. Substance P Inhibits Hyperosmotic Stress-Induced Apoptosis in Corneal Epithelial Cells through the Mechanism of Akt Activation and Reactive Oxygen Species Scavenging via the Neurokinin-1 Receptor

    PubMed Central

    Yang, Lingling; Sui, Wenjie; Li, Yunqiu; Qi, Xia; Wang, Yao; Zhou, Qingjun; Gao, Hua

    2016-01-01

    Hyperosmolarity has been recognized as an important pathological factor in dry eye leading to ocular discomfort and damage. As one of the major neuropeptides of corneal innervation, substance P (SP) has been shown to possess anti-apoptotic effects in various cells. The aim of this study was to determine the capacity and mechanism of SP against hyperosmotic stress-induced apoptosis in cultured corneal epithelial cells. The cells were exposed to hyperosmotic stress by the addition of high glucose in the presence or absence of SP. The results showed that SP inhibited hyperosmotic stress-induced apoptosis of mouse corneal epithelial cells. Moreover, SP promoted the recovery of phosphorylated Akt level, mitochondrial membrane potential, Ca2+ contents, intracellular reactive oxygen species (ROS) and glutathione levels that impaired by hyperosmotic stress. However, the antiapoptotic capacity of SP was partially suppressed by Akt inhibitor or glutathione depleting agent, while the neurokinin-1 (NK-1) receptor antagonist impaired Akt activation and ROS scavenging that promoted by SP addition. In conclusion, SP protects corneal epithelial cells from hyperosmotic stress-induced apoptosis through the mechanism of Akt activation and ROS scavenging via the NK-1 receptor. PMID:26901348

  18. Levels of interleukin-6, superoxide dismutase and malondialdehyde in the lung tissue of a rat model of hypoxia-induced acute pulmonary edema

    PubMed Central

    GAO, HENGBO; TIAN, YINGPING; WANG, WEI; YAO, DONGQI; ZHENG, TUOKANG; MENG, QINGBING

    2016-01-01

    The present study aimed to investigate the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and interleukin (IL)-6 in the lung tissue of a rat model of acute pulmonary edema induced by acute hypoxia, and its pathophysiological significance. A total of 48 adult Wistar rats were randomly divided into group A, a normal group; group B, a model of acute pulmonary edema induced by hypoxia for 24 h; group C, a model of acute pulmonary edema induced by hypoxia for 48 h; and group D, a model of acute pulmonary edema induced by hypoxia for 72 h. The rats in groups B-D were intraperitoneally injected with 6% ammonium chloride to establish the model of acute pulmonary edema, and were subsequently sacrificed following successful modeling for 24, 48 and 72 h. The plasma of rats was isolated and the lungs of the rats were removed. Subsequently, a 10% lung homogenate was prepared and the contents and the activities of MDA, SOD and IL-6 in the lung tissue and IL-6 in the plasma were detected by enzyme-linked immunosorbent assay. MDA and IL-6 expression levels increased and SOD activity decreased in the lung tissue in group B as compared with group A; however the difference did not reach significance (P>0.05). MDA, IL-6 and SOD levels in the lung tissue of rats were significantly altered following the increased duration of pulmonary edema in groups C and D, as compared group A (P<0.05). The plasma IL-6 levels of the rats in groups B-D significantly increased, as compared with those in group A (P<0.05). In conclusion, the results of the present study demonstrated that the incidence of acute pulmonary edema may be associated with oxidative stress. Furthermore, decreased antioxidant capacity and increased free radical levels may be associated with pulmonary edema, as in the present study the levels of IL-6, SOD and MDA in the lung tissue were observed to be associated with the pathological changes of the disease. PMID:26998026

  19. The genetics of Fuchs′ corneal dystrophy

    PubMed Central

    Iliff, Benjamin W; Riazuddin, S Amer; Gottsch, John D

    2013-01-01

    Fuchs′ corneal dystrophy (FCD) is a common late-onset genetic disorder of the corneal endothelium. It causes loss of endothelial cell density and excrescences in the Descemet membrane, eventually progressing to corneal edema, necessitating corneal transplantation. The genetic basis of FCD is complex and heterogeneous, demonstrating variable expressivity and incomplete penetrance. To date, three causal genes, ZEB1, SLC4A11 and LOXHD1, have been identified, representing a small proportion of the total genetic load of FCD. An additional four loci have been localized, including a region on chromosome 18 that is potentially responsible for a large proportion of all FCD cases. The elucidation of the causal genes underlying these loci will begin to clarify the pathogenesis of FCD and pave the way for the emergence of nonsurgical treatments. PMID:23585771

  20. Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology

    SciTech Connect

    Testylier, Guy . E-mail: guytestylier@crssa.net; Lahrech, Hana; Montigon, Olivier; Foquin, Annie; Delacour, Claire; Bernabe, Denis; Segebarth, Christoph; Dorandeu, Frederic; Carpentier, Pierre

    2007-04-15

    Purpose: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. Methods: Three hours and 24 h after the intoxication with soman (172 {mu}g/kg), the mice were anesthetized with an isoflurane/N{sub 2}O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. Results: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. Conclusions: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into Brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures.

  1. Anti-asthmatic agents alleviate pulmonary edema by upregulating AQP1 and AQP5 expression in the lungs of mice with OVA-induced asthma.

    PubMed

    Dong, Chunling; Wang, Guifang; Li, Bo; Xiao, Kui; Ma, Zhongsen; Huang, Hua; Wang, Xiangdong; Bai, Chunxue

    2012-04-15

    Ovalbumin (OVA)-induced asthma in mouse lungs causes changes in the mRNA and protein levels of aquaporins (AQPs). AQP expression was examined in the presence of various anti-asthmatic agents, including dexamethasone, ambroxol, and terbutaline. The influence of these agents on OVA-induced airway inflammation was also evaluated. The mRNA expression levels of AQP1, 4, and 5 were significantly reduced and that of AQP3 was significantly increased 24h after the last OVA exposure. The protein levels of AQP1, 3, and 5 mirrored the mRNA expression profiles, but AQP4 did not exhibit any changes. Only the mRNA and protein expression levels of AQP1 and AQP5 were significantly increased by these three anti-asthmatic agents. Dexamethasone and ambroxol improved the eosinophil infiltration, mucus secretion, and pulmonary edema caused by OVA, but terbutaline only alleviated pulmonary edema. These results indicate that AQP1 and AQP5 are closely related to pulmonary edema but not to eosinophil infiltration or mucus secretion during asthma. Anti-asthmatic agents could alleviate pulmonary edema through upregulating the expression of AQP1 and AQP5 in mouse lungs that have OVA-induced asthma. PMID:22226856

  2. Macular edema-like change and pseudopapilledema in a case of Scheie syndrome.

    PubMed

    Usui, T; Shirakashi, M; Takagi, M; Abe, H; Iwata, K

    1991-09-01

    We reported a case of Scheie syndrome in which diffuse fine corneal deposits, pigmentary retinal degeneration, pseudopapilledema, and macular edema-like change were observed bilaterally. This is the first report describing macular change in Scheie syndrome. PMID:1836802

  3. Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals.

    PubMed

    Kovács, Illés; Dienes, Lóránt; Perényi, Kristóf; Quirce, Susana; Luna, Carolina; Mizerska, Kamila; Acosta, M Carmen; Belmonte, Carlos; Gallar, Juana

    2016-09-15

    Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34°C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals. The characteristics of the spontaneous and the stimulus-evoked (cooling ramps from 34°C to 15°C) activity before and in presence of lacosamide 100µM and lidocaine 100µM were compared. Cold nerve terminals (n=34) recorded from dry eye corneas showed significantly enhanced spontaneous activity (8.0±1.1 vs. 5.2±0.7imp/s; P<0.05) and cold response (21.2±1.7 vs. 16.8±1.3imp/s; P<0.05) as well as reduced cold threshold (1.5±0.1 vs. 2.8±0.2 Δ°C; P<0.05) to cooling ramps compared to terminals (n=58) from control animals. Both lacosamide and lidocaine decreased spontaneous activity and peak response to cooling ramps significantly (P<0.05). Temperature threshold was increased by the addition of lidocaine (P<0.05) but not lacosamide (P>0.05) to the irrigation fluid. In summary, the application of lacosamide results in a significant decrease of the augmented spontaneous activity and responsiveness to cold of corneal sensory nerves from tear-deficient animals. Based on these promising results we speculate that lacosamide might be used to reduce the hyperexcitability of corneal cold receptors caused by prolonged ocular surface dryness due to hyposecretory or evaporative dry eye disease. PMID:27263827

  4. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

    PubMed

    Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

    2016-04-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes. PMID:25833102

  5. Molecular Bases of Corneal Endothelial Dystrophies

    PubMed Central

    Schmedt, Thore; Silva, Mariana Mazzini; Ziaei, Alireza; Jurkunas, Ula

    2011-01-01

    The phrase “corneal endothelial dystrophies” embraces a group of bilateral corneal conditions that are characterized by a non-inflammatory and progressive degradation of corneal endothelium. Corneal endothelial cells exhibit a high pump site density and, along with barrier function, are responsible for maintaining the cornea in its natural state of relative dehydration. Gradual loss of endothelial cells leads to an insufficient water outflow, resulting in corneal edema and loss of vision. Since the pathologic mechanisms remain largely unknown, the only current treatment option is surgical transplantation when vision is severely impaired. In the past decade, important steps have been taken to understand how endothelial degeneration progresses on the molecular level. Studies of affected multigenerational families and sporadic cases identified genes and chromosomal loci, and revealed either Mendelian or complex disorder inheritance patterns. Mutations have been detected in genes that carry important structural, metabolic, cytoprotective, and regulatory functions in corneal endothelium. In addition to genetic predisposition, environmental factors like oxidative stress were found to be involved in the pathogenesis of endotheliopathies. This review summarizes and crosslinks the recent progress on deciphering the molecular bases of corneal endothelial dystrophies. PMID:21855542

  6. Lysophosphatidic acid induces YAP-promoted proliferation of human corneal endothelial cells via PI3K and ROCK pathways

    PubMed Central

    Hsueh, Yi-Jen; Chen, Hung-Chi; Wu, Sung-En; Wang, Tze-Kai; Chen, Jan-Kan; Ma, David Hui-Kang

    2015-01-01

    The first two authors contributed equally to this work.Silence of p120-catenin has shown promise in inducing proliferation in human corneal endothelial cells (HCECs), but there is concern regarding off-target effects in potential clinical applications. We aimed to develop ex vivo expansion of HCECs using natural compounds, and we hypothesized that lysophosphatidic acid (LPA) can unlock the mitotic block in contact-inhibited HCECs via enhancing nuclear translocation of yes-associated protein (YAP). Firstly, we verified that exogenous YAP could induce cell proliferation in contact-inhibited HCEC monolayers and postconfluent B4G12 cells. In B4G12 cells, enhanced cyclin D1 expression, reduced p27KIP1/p21CIP1 levels, and the G1/S transition were detected upon transfection with YAP. Secondly, we confirmed that LPA induced nuclear expression of YAP and promoted cell proliferation. Moreover, PI3K and ROCK, but not ERK or p38, were required for LPA-induced YAP nuclear translocation. Finally, cells treated with LPA or transfected with YAP remained hexagonal in shape, in addition to unchanged expression of ZO-1, Na/K-ATPase, and smooth muscle actin (SMA), suggestive of a preserved phenotype, without endothelial–mesenchymal transition. Collectively, our findings indicate an innovative strategy for ex vivo cultivation of HCECs for transplantation and cell therapy. PMID:26029725

  7. Anti-Inflammatory and Antioxidant Effects of Repeated Exposure to Cruciferous Allyl Nitrile in Sensitizer-Induced Ear Edema in Mice

    PubMed Central

    Tanii, Hideji; Sugitani, Kayo; Saijoh, Kiyofumi

    2016-01-01

    Background Skin sensitizers induce allergic reactions through the induction of reactive oxygen species. Allyl nitrile from cruciferous vegetables has been reported to induce antioxidants and phase II detoxification enzymes in various tissues. We assessed the effects of repeated exposure to allyl nitrile on sensitizer-induced allergic reactions. Material/Methods Mice were dosed with allyl nitrile (0–200 μmol/kg), and then received a dermal application of 1 of 3 sensitizers on the left ear or 1 of 2 vehicles on the right ear. Quantitative assessment of edema was carried out by measuring the difference in weight between the portions taken from the right and left ears. We tested enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) in ears. Results Repeated exposure to allyl nitrile reduced edemas induced by glutaraldehyde and by 2, 4-dinitrochlorobenzene (DNCB), but not by formaldehyde. The repeated exposure decreased levels of TBARS, a marker of oxidative stress, induced by glutaraldehyde and by DNCB, but not by formaldehyde. Allyl nitrile elevated SOD levels for the 3 sensitizers, and CAT levels for formaldehyde and DNCB. Allyl nitrile also increased GPx levels for formaldehyde and DNCB, but not for glutaraldehyde. The reduced edemas were associated with changes in oxidative stress levels and antioxidant enzymes. Conclusions Repeated exposure to allyl nitrile reduced allergic reactions induced by glutaraldehyde and by DNCB, but not by formaldehyde. This reduction was associated with changes in ROS levels and antioxidant enzyme activities. PMID:26932717

  8. The role of free radicals in paraquat-induced corneal lesions.

    PubMed

    Nordquist, R E; Nguyen, H; Poyer, J L; Carubelli, R

    1995-07-01

    Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant. Enzyme-catalyzed redoxcycling of paraquat generates oxygen radicals. The toxic, even lethal, effects of paraquat are due to free radical-mediated tissue injury. Ocular lesions, sometimes quite severe, have been observed following accidental splashing of paraquat solutions onto the eyes. These studies were designed to document the generation of paraquat free radicals in corneal tissue, and to describe the histological nature of the corneal injuries in experimental animals (rabbits and monkeys). The EPR spectrum of rabbit corneas, 30 min. after intrastromal injection of paraquat, showed the signal of the free radical of paraquat. Ultrastructural studies of corneas 8 days after intrastromal injections (100 microliters) of paraquat solutions showed that the initial lesions occur at the epithelium/basement membrane interface. In rabbit cornea, dose dependent lesions were observed, i.e. whereas 50 mM paraquat caused only minimal damage to the epithelial basement membrane, 75 mM caused complete dissolution to the basement membrane with some damage to stromal collagen, and loss of epithelium with stromal ulceration and severe inflammatory response were observed with 150 mM paraquat. Monkey corneas were less susceptible than those of rabbits to the effects of paraquat. No lesions were observed following intrastromal injections of 50 mM or 75 mM paraquat. With higher concentrations of paraquat (100 mM and 150 mM) the primary injuries were to the proximal and lateral plasma membranes of basal epithelial cells; basement membrane alterations were detected only adjacent to areas of significant plasma membrane damage. The underlying Bowman's membrane and stroma were not affected. Anatomical differences between the corneas of rabbit and monkeys as well as possible biochemical differences may account for the species differences observed. PMID:7647920

  9. Tissue-type transglutaminase and the effects of cystamine on intracerebral hemorrhage-induced brain edema and neurological deficits

    PubMed Central

    Okauchi, Masanobu; Xi, Guohua; Keep, Richard F.; Hua, Ya

    2009-01-01

    Introduction Neurodegeneration occurs after intracerebral hemorrhage (ICH) and tissue-type transglutaminase (tTG) has a role in neurodegenerative disorders. The present study investigated tTG expression after ICH and the effects of a tTG inhibitor, cystamine, on ICH-induced brain edema and neurological deficits. Methods This study had two parts. In the first, male Sprague-Dawley rats received an intracaudate injection of 100 µL autologous whole blood or a needle insertion (sham). Rats were killed 3 days later and the brains used for immunohistochemistry, Western blots and real-time quantitative polymerase chain reaction. In the second set, ICH rats were treated intraperitoneally with either a tTG inhibitor, cystamine, or vehicle. Rats underwent behavioral testing and were killed at day-3 for measurement of brain swelling. Results tTG positive cells were found in the ipsilateral basal ganglia after ICH and most of those cells were neuron-like. Western blot analysis showed a 3-fold increase in tTG in the ipsilateral basal ganglia (p<0.01 vs. sham) after ICH. tTG mRNA levels were also significantly higher (8.5-fold increase vs. sham). Cystamine treatment attenuated ICH-induced brain swelling (day 3: 14.4±3.2 vs. 21.4±4.0% in vehicle-treated rats, p<0.01), neuronal death and improved functional outcome (forelimb placing score: 47±23 vs. 17±16% in vehicle-treated rats, p<0.05). Conclusions ICH induces perihematomal tTG upregulation and cystamine, a tTG inhibitor, reduces ICH-induced brain swelling and neurological deficits. PMID:19007756

  10. Contribution of TNFalpha, IL-1beta and CINC-1 for articular incapacitation, edema and cell migration in a model of LPS-induced reactive arthritis.

    PubMed

    Bressan, Elisângela; Cunha, Fernando De Queiroz; Tonussi, Carlos Rogério

    2006-10-01

    The protective effect of anti-CINC-1, -TNFalpha and -IL-1beta antisera on articular inflammatory incapacitation, articular diameter and synovial fluid cell content, which are correlated to nociception, edema and cell migration, respectively, were evaluated in a rat model of LPS-induced reactive arthritis. In this model, Escherichia coli lipopolysaccharide (LPS; 30 ng) was injected in a knee-joint previously primed with carrageenan (300 microg). Articular incapacitation was evaluated hourly by the automated registering of the knee-joint function during animal walking, and the knee-joint edema was evaluated by measuring the articular diameter increase. After 6 h, the animals were euthanized for collecting synovial fluid for the evaluation of cell migration. LPS produced dose-dependent incapacitation and edema. Anti-TNFalpha, -IL-1beta, and -CINC-1 antisera (20 and 40 microl) were used as pretreatment into knee-joint before LPS injection. At higher dose, Anti-TNFalpha and anti-CINC-1 were able to inhibit incapacitation, articular edema and mononuclear (MON) migration. Anti-IL1beta did not affect incapacitation at any dose, although inhibited edema and cell migration. Surprisingly, the higher dose of anti-IL1beta antisera did not inhibit cell migration, although inhibited articular edema. These findings corroborate the role TNFalpha has in different forms of arthritis, but points out the idea that CINC-1 (the homologue for human IL-8) may constitute a promising target for reactive arthritis management. Indeed, the potent antiedematogenic effect, and principally the anti-migration effect of anti-CINC-1, raises the possibility of a better control of disease progression than with anti-IL-1beta therapies. PMID:17166735

  11. LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp).

    PubMed

    Poulsen, Ebbe Toftgaard; Nielsen, Nadia Sukusu; Jensen, Morten M; Nielsen, Esben; Hjortdal, Jesper; Kim, Eung Kweon; Enghild, Jan J

    2016-02-01

    More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals. PMID:26864644

  12. Imaging, Reconstruction, And Display Of Corneal Topography

    NASA Astrophysics Data System (ADS)

    Klyce, Stephen D.; Wilson, Steven E.

    1989-12-01

    The cornea is the major refractive element in the eye; even minor surface distortions can produce a significant reduction in visual acuity. Standard clinical methods used to evaluate corneal shape include keratometry, which assumes the cornea is ellipsoidal in shape, and photokeratoscopy, which images a series of concentric light rings on the corneal surface. These methods fail to document many of the corneal distortions that can degrade visual acuity. Algorithms have been developed to reconstruct the three dimensional shape of the cornea from keratoscope images, and to present these data in the clinically useful display of color-coded contour maps of corneal surface power. This approach has been implemented on a new generation video keratoscope system (Computed Anatomy, Inc.) with rapid automatic digitization of the image rings by a rule-based approach. The system has found clinical use in the early diagnosis of corneal shape anomalies such as keratoconus and contact lens-induced corneal warpage, in the evaluation of cataract and corneal transplant procedures, and in the assessment of corneal refractive surgical procedures. Currently, ray tracing techniques are being used to correlate corneal surface topography with potential visual acuity in an effort to more fully understand the tolerances of corneal shape consistent with good vision and to help determine the site of dysfunction in the visually impaired.

  13. Corneal Neovascularization: An Anti-VEGF Therapy Review

    PubMed Central

    Chang, Jin-Hong; Garg, Nitin K.; Lunde, Elisa; Han, Kyu-Yeon; Jain, Sandeep; Azar, Dimitri T.

    2013-01-01

    Corneal neovascularization is a serious condition that can lead to a profound decline in vision. The abnormal vessels block light, cause corneal scarring, compromise visual acuity, and may lead to inflammation and edema. Corneal neovascularization occurs when the balance between angiogenic and antiangiogenic factors is tipped toward angiogenic molecules. Vascular endothelial growth factor (VEGF), one of the most important mediators of angiogenesis, is upregulated during neovascularization. In fact, anti-VEGF agents have efficacy in the treatment of neovascular age-related macular degeneration, diabetic retinopathy, macular edema, neovascular glaucoma, and other neovascular diseases. These same agents have great potential for the treatment of corneal neovascularization. We review some of the most promising anti-VEGF therapies, including bevacizumab, VEGF trap, siRNA, and tyrosine kinase inhibitors. PMID:22898649

  14. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice

    PubMed Central

    Gupta, Ashok Kumar; Parasar, Devraj; Sagar, Amin; Choudhary, Vikas; Chopra, Bhupinder Singh; Garg, Renu; Ashish; Khatri, Neeraj

    2015-01-01

    Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse) in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse) compared with anti-inflammatory drug diclofenac sodium (10 mg/kg)] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histo-pathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model. PMID:26426535

  15. pH Induced Conformational Transitions in the Transforming Growth Factor β-Induced Protein (TGFβIp) Associated Corneal Dystrophy Mutants

    PubMed Central

    Murugan, Elavazhagan; Venkatraman, Anandalakshmi; Lei, Zhou; Mouvet, Victoria; Rui Yi Lim, Rayne; Muruganantham, Nandhakumar; Goh, Eunice; Swee Lim Peh, Gary; Beuerman, Roger W.; Chaurasia, Shyam S.; Rajamani, Lakshminarayanan; Mehta, Jodhbir S.

    2016-01-01

    Most stromal corneal dystrophies are associated with aggregation and deposition of the mutated transforming growth factor-β induced protein (TGFβIp). The 4th_FAS1 domain of TGFβIp harbors ~80% of the mutations that forms amyloidogenic and non-amyloidogenic aggregates. To understand the mechanism of aggregation and the differences between the amyloidogenic and non-amyloidogenic phenotypes, we expressed the 4th_FAS1 domains of TGFβIp carrying the mutations R555W (non-amyloidogenic) and H572R (amyloidogenic) along with the wild-type (WT). R555W was more susceptible to acidic pH compared to H572R and displayed varying chemical stabilities with decreasing pH. Thermal denaturation studies at acidic pH showed that while WT did not undergo any conformational transition, the mutants exhibited a clear pH-dependent irreversible conversion from αβ conformation to β-sheet oligomers. The β-oligomers of both mutants were stable at physiological temperature and pH. Electron microscopy and dynamic light scattering studies showed that β-oligomers of H572R were larger compared to R555W. The β-oligomers of both mutants were cytotoxic to primary human corneal stromal fibroblast (pHCSF) cells. The β-oligomers of both mutants exhibit variations in their morphologies, sizes, thermal and chemical stabilities, aggregation patterns and cytotoxicities. PMID:27030015

  16. Pimaradienoic Acid Inhibits Carrageenan-Induced Inflammatory Leukocyte Recruitment and Edema in Mice: Inhibition of Oxidative Stress, Nitric Oxide and Cytokine Production

    PubMed Central

    Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    Pimaradienoic acid (PA; ent-pimara-8(14),15-dien-19-oic acid) is a pimarane diterpene found in plants such as Vigueira arenaria Baker (Asteraceae) in the Brazilian savannas. Although there is evidence on the analgesic and in vitro inhibition of inflammatory signaling pathways, and paw edema by PA, its anti-inflammatory effect deserves further investigation. Thus, the objective of present study was to investigate the anti-inflammatory effect of PA in carrageenan-induced peritoneal and paw inflammation in mice. Firstly, we assessed the effect of PA in carrageenan-induced leukocyte recruitment in the peritoneal cavity and paw edema and myeloperoxidase activity. Next, we investigated the mechanisms involved in the anti-inflammatory effect of PA. The effect of PA on carrageenan-induced oxidative stress in the paw skin and peritoneal cavity was assessed. We also tested the effect of PA on nitric oxide, superoxide anion, and inflammatory cytokine production in the peritoneal cavity. PA inhibited carrageenan-induced recruitment of total leukocytes and neutrophils to the peritoneal cavity in a dose-dependent manner. PA also inhibited carrageenan-induced paw edema and myeloperoxidase activity in the paw skin. The anti-inflammatory mechanism of PA depended on maintaining paw skin antioxidant activity as observed by the levels of reduced glutathione, ability to scavenge the ABTS cation and reduce iron as well as by the inhibition of superoxide anion and nitric oxide production in the peritoneal cavity. Furthermore, PA inhibited carrageenan-induced peritoneal production of inflammatory cytokines TNF-α and IL-1β. PA presents prominent anti-inflammatory effect in carrageenan-induced inflammation by reducing oxidative stress, nitric oxide, and cytokine production. Therefore, it seems to be a promising anti-inflammatory molecule that merits further investigation. PMID:26895409

  17. Pimaradienoic Acid Inhibits Carrageenan-Induced Inflammatory Leukocyte Recruitment and Edema in Mice: Inhibition of Oxidative Stress, Nitric Oxide and Cytokine Production.

    PubMed

    Mizokami, Sandra S; Hohmann, Miriam S N; Staurengo-Ferrari, Larissa; Carvalho, Thacyana T; Zarpelon, Ana C; Possebon, Maria I; de Souza, Anderson R; Veneziani, Rodrigo C S; Arakawa, Nilton S; Casagrande, Rubia; Verri, Waldiceu A

    2016-01-01

    Pimaradienoic acid (PA; ent-pimara-8(14),15-dien-19-oic acid) is a pimarane diterpene found in plants such as Vigueira arenaria Baker (Asteraceae) in the Brazilian savannas. Although there is evidence on the analgesic and in vitro inhibition of inflammatory signaling pathways, and paw edema by PA, its anti-inflammatory effect deserves further investigation. Thus, the objective of present study was to investigate the anti-inflammatory effect of PA in carrageenan-induced peritoneal and paw inflammation in mice. Firstly, we assessed the effect of PA in carrageenan-induced leukocyte recruitment in the peritoneal cavity and paw edema and myeloperoxidase activity. Next, we investigated the mechanisms involved in the anti-inflammatory effect of PA. The effect of PA on carrageenan-induced oxidative stress in the paw skin and peritoneal cavity was assessed. We also tested the effect of PA on nitric oxide, superoxide anion, and inflammatory cytokine production in the peritoneal cavity. PA inhibited carrageenan-induced recruitment of total leukocytes and neutrophils to the peritoneal cavity in a dose-dependent manner. PA also inhibited carrageenan-induced paw edema and myeloperoxidase activity in the paw skin. The anti-inflammatory mechanism of PA depended on maintaining paw skin antioxidant activity as observed by the levels of reduced glutathione, ability to scavenge the ABTS cation and reduce iron as well as by the inhibition of superoxide anion and nitric oxide production in the peritoneal cavity. Furthermore, PA inhibited carrageenan-induced peritoneal production of inflammatory cytokines TNF-α and IL-1β. PA presents prominent anti-inflammatory effect in carrageenan-induced inflammation by reducing oxidative stress, nitric oxide, and cytokine production. Therefore, it seems to be a promising anti-inflammatory molecule that merits further investigation. PMID:26895409

  18. 4-Hydroxyphenylacetic Acid Attenuated Inflammation and Edema via Suppressing HIF-1α in Seawater Aspiration-Induced Lung Injury in Rats

    PubMed Central

    Liu, Zhongyang; Xi, Ronggang; Zhang, Zhiran; Li, Wangping; Liu, Yan; Jin, Faguang; Wang, Xiaobo

    2014-01-01

    4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats. PMID:25050781

  19. Penetrating keratoplasty restoring vision in an unusual case of corneal opacity following exposure to Euphorbia latex.

    PubMed

    Dutta, Jayanta; Choudhury, Somnath; Lahiri, Kapildeb; Savale, Smruti; Banerjee, Monideepa; Datta, Himadri

    2015-10-01

    The milky sap of the Euphorbia plant is highly toxic and causes inflammation to the skin and eyes. Damage to the eye ranges from superficial epithelial defects, keratoconjunctivitis, mild to moderate corneal edema, anterior uveitis, Descemet membrane folds, raised intraocular pressure and rarely corneal opacity in severe untreated cases. Here we report a case of visual restoration by optical penetrating keratoplasty in a patient with severe corneal opacity following exposure to Euphorbia latex. PMID:25540165

  20. Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

    PubMed

    Kimura, Louise F; Prezotto-Neto, José Pedro; Távora, Bianca C L F; Faquim-Mauro, Eliana L; Pereira, Nicole A; Antoniazzi, Marta M; Jared, Simone G S; Teixeira, Catarina F P; Santoro, Marcelo L; Barbaro, Katia C

    2015-09-01

    This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays. PMID:26100666

  1. [MODELING INFLAMMATORY EDEMA: ARE THE MODELS INTERCHANGEABLE].

    PubMed

    Hanh, Cong Hong; Khaziakhmetova, V N; Ziganshina, L E

    2015-01-01

    Experimental modeling of inflammatory edema by sub-plantar injection of carrageenan and formalin in mice and rats is widely used to evaluate potential anti-inflammatory activity of new drugs. This systematic analysis of published data showed that carrageenan induced paw edema model is used for evaluating the anti-inflammatory activity mostly in rats rather than mice. Formalin induced paw edema in rats and mice is used primarily for evaluation of the analgesic activity of drugs. Taken together, the results of this systematic review of available literature on edema modeling substantiate recommendation to use carrageenan paw edema in rats and formalin paw edema in mice as complementary, but not interchangeable models of inflammation. PMID:26591204

  2. Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy

    PubMed Central

    Ferdousi, Maryam; Azmi, Shazli; Petropoulos, Ioannis Nikolaos; Fadavi, Hassan; Ponirakis, Georgios; Marshall, Andrew; Tavakoli, Mitra; Malik, Imaan; Mansoor, Wasat; Malik, Rayaz Ahmed

    2015-01-01

    There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration. PMID:26430773

  3. Effects of one minute and ten minutes of walking activity in rats with arthritis induced by complete Freund's adjuvant on pain and edema symptoms.

    PubMed

    Gomes, Raquel Pinheiro; Bressan, Elisângela; Silva, Tatiane Morgana da; Gevaerd, Monique da Silva; Tonussi, Carlos Rogério; Domenech, Susana Cristina

    2014-01-01

    This study evaluated the effects of two protocols of exercise on nociception, edema and cell migration in rats with CFA-induced arthritis. Female Wistar rats (200 - 250 g, n = 50) was monoarthritis-induced by complete Freund's adjuvant (CFA; Mycobacterium butyricum, 0.5 mg/mL; 50 μL) into the right knee joint (TF; n = 24) or right ankle joint (TT; n = 26). Incapacitation was measured by the paw elevation time (TEP; s) in 1-min periods of observation. The edema of the knee or ankle joints was evaluated by the variation of the articular diameter (DA, cm) and by the paw volume variation (EP, mL), respectively. Both were measured during 10 consecutive days. Two protocols of exercise were performed: (a) in the constant exercise group (TF, n = 6; TT, n = 6) performing 1 minute of daily exercise on the cylinder; (b) variable exercise group (TF, n = 6; TT, n = 7), the exercise increased by 1 minute per day. The control groups (TF, n = 12; TT, n = 13) didn't perform the exercise. After 10 days, the animals were euthanized for total (CT; cells/mm3) and differential leukocyte counts (mononuclear - MON, and polymorphonuclear - PMN, cells/mm3) of the articular inflammatory exudate. The variable exercise protocol inhibited incapacitation and edema for both joints. However, cell migration decreased only in the TF.The constant exercise reduced edema in both joints, and cell migration was decreased in the TT. However, the incapacitation was not reduced. Variable exercise seemed to be more effective in reducing the inflammatory parameters than constant exercise. PMID:24878853

  4. Gelam Honey Inhibits the Production of Proinflammatory, Mediators NO, PGE(2), TNF-α, and IL-6 in Carrageenan-Induced Acute Paw Edema in Rats.

    PubMed

    Hussein, Saba Zuhair; Mohd Yusoff, Kamaruddin; Makpol, Suzana; Mohd Yusof, Yasmin Anum

    2012-01-01

    Natural honey is well known for its therapeutic value and has been used in traditional medicine of different cultures throughout the world. The aim of this study was to investigate the anti-inflammatory effect of Malaysian Gelam honey in inflammation-induced rats. Paw edema was induced by a subplantar injection of 1% carrageenan into the rat right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) Indomethacin (10 mg/kg, p.o.) or Gelam honey at different doses (1 or 2 g/kg, p.o.). The increase in footpad thickness was considered to be edema, which was measured using a dial caliper. Plasma and paw tissue were collected to analyze the production of inflammatory mediators, such as NO, PGE(2), TNF-α, and IL-6, as well as iNOS and COX-2. The results showed that Gelam honey could reduce edema in a dose-dependent fashion in inflamed rat paws, decrease the production of NO, PGE(2), TNF-α, and IL-6 in plasma, and suppress the expression of iNOS, COX-2, TNF-α, and IL-6 in paw tissue. Oral pretreatment of Gelam honey at 2 g/kg of body weight at two time points (1 and 7 days) showed a significantly decreased production of proinflammatory cytokines, which was similar to the effect of the anti-inflammatory drug Indomethacin (NSAID), both in plasma and tissue. Thus, our results suggest that Gelam honey has anti-inflammatory effects by reducing the rat paw edema size and inhibiting the production of proinflammatory mediators. Gelam honey is potentially useful for treating inflammatory conditions. PMID:22919407

  5. The Impact of Type 1 Diabetes Mellitus on Corneal Epithelial Nerve Morphology and the Corneal Epithelium

    PubMed Central

    Cai, Daniel; Zhu, Meifang; Petroll, W. Matthew; Koppaka, Vindhya; Robertson, Danielle M.

    2015-01-01

    Diabetic corneal neuropathy can result in chronic, sight-threatening corneal pathology. Although the exact etiology is unknown, it is believed that a reduction in corneal sensitivity and loss of neurotrophic support contributes to corneal disease. Information regarding the relationship between nerve loss and effects on the corneal epithelium is limited. We investigated changes in the corneal epithelium and nerve morphology using three-dimensional imaging in vivo and in situ in a streptozotocin-induced diabetic mouse model. Streptozotocin-treated mice showed increased levels of serum glucose and growth retardation consistent with a severe diabetic state. A reduction in the length of the subbasal nerve plexus was evident after 6 weeks of disease. Loss of the subbasal nerve plexus was associated with corneal epithelial thinning and a reduction in basal epithelial cell density. In contrast, loss of the terminal epithelial nerves was associated with animal age. Importantly, this is the first rodent model of type 1 diabetes that shows characteristics of corneal epithelial thinning and a reduction in basal epithelial cell density, both previously have been documented in humans with diabetic corneal neuropathy. These findings indicate that in type 1 diabetes, nerve fiber damage is evident in the subbasal nerve plexus before terminal epithelial nerve loss and that neurotrophic support from both the subbasal nerve plexus and terminal epithelial nerves is essential for the maintenance of corneal epithelial homeostasis. PMID:25102563

  6. The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium.

    PubMed

    Cai, Daniel; Zhu, Meifang; Petroll, W Matthew; Koppaka, Vindhya; Robertson, Danielle M

    2014-10-01

    Diabetic corneal neuropathy can result in chronic, sight-threatening corneal pathology. Although the exact etiology is unknown, it is believed that a reduction in corneal sensitivity and loss of neurotrophic support contributes to corneal disease. Information regarding the relationship between nerve loss and effects on the corneal epithelium is limited. We investigated changes in the corneal epithelium and nerve morphology using three-dimensional imaging in vivo and in situ in a streptozotocin-induced diabetic mouse model. Streptozotocin-treated mice showed increased levels of serum glucose and growth retardation consistent with a severe diabetic state. A reduction in the length of the subbasal nerve plexus was evident after 6 weeks of disease. Loss of the subbasal nerve plexus was associated with corneal epithelial thinning and a reduction in basal epithelial cell density. In contrast, loss of the terminal epithelial nerves was associated with animal age. Importantly, this is the first rodent model of type 1 diabetes that shows characteristics of corneal epithelial thinning and a reduction in basal epithelial cell density, both previously have been documented in humans with diabetic corneal neuropathy. These findings indicate that in type 1 diabetes, nerve fiber damage is evident in the subbasal nerve plexus before terminal epithelial nerve loss and that neurotrophic support from both the subbasal nerve plexus and terminal epithelial nerves is essential for the maintenance of corneal epithelial homeostasis. PMID:25102563

  7. Involvement of the extrinsic and intrinsic pathways in ultraviolet B-induced apoptosis of corneal epithelial cells.

    PubMed

    Ubels, John L; Glupker, Courtney D; Schotanus, Mark P; Haarsma, Loren D

    2016-04-01

    The goal of this study was to elucidate the pathway by which UVB initiates efflux of K(+) and subsequently apoptosis in human corneal limbal epithelial (HCLE) cells. The initial focus of the study was on the extrinsic pathway involving Fas. HCLE cells transfected with Fas siRNA were exposed to 80-150 mJ/cm(2) UVB and incubated in culture medium with 5.5 mM K(+). Knockdown of Fas resulted in limited reduction in UVB-induced caspase-8 and -3 activity. Patch-clamp recordings showed no difference in UVB-induced normalized K(+) currents between Fas transfected and control cells. Knockdown of caspase-8 had no effect on the activation of caspase-3 following UVB exposure, while a caspase-8 inhibitor completely eliminated UVB activation of caspase-3. This suggests that caspase-8 is a robust enzyme, able to activate caspase-3 via residual caspase-8 present after knockdown, and that caspase-8 is directly involved in the UVB activation of caspase-3. Inhibition of caspase-9 significantly decreased the activation of caspases-8 and -3 in response to UVB. Knockdown of Apaf-1, required for activation of caspase-9, resulted in a significant reduction in UVB-induced activation of caspases-9, -8, and -3. Knockdown of Apaf-1 also inhibited intrinsic and UVB-induced levels of apoptosis, as determined by DNA fragmentation measured by TUNEL assay. In UVB exposed cultures treated with caspase-3 inhibitor, the percentage of apoptotic cells was reduced to control levels, confirming the necessity of caspase-3 activation in DNA fragmentation. The lack of effect of Fas knockdown on K(+) channel activation, as well as the limited effect on activation of caspases-8 and -3, strongly suggest that Fas and the extrinsic pathway is not of primary importance in the initiation of apoptosis in response to UVB in HCLE cells. Inhibition of caspase-8 and -3 activation following inhibition of caspase-9, as well as reduction in activation of caspases-9, -8, and -3 and DNA fragmentation in response to Apaf

  8. Targeted Overexpression of TGF-α in the Corneal Epithelium of Adult Transgenic Mice Induces Changes in Anterior Segment Morphology and Activates Noncanonical Wnt Signaling

    PubMed Central

    Yuan, Yong; Yeh, Lung-Kun; Liu, Hongshan; Yamanaka, Osamu; Hardie, William D.; Kao, Winston W.-Y.; Liu, Chia-Yang

    2013-01-01

    Purpose. Transforming growth factor-alpha (TGF-α) transduces its signal through the epidermal growth factor receptor and is essential for corneal epithelial homeostasis. Previous studies have demonstrated that overexpression of TGF-α in the developing eye leads to anterior segment dysgenesis. However, the underlying mechanisms remain unclear. Here we examined the effects of TGF-α overexpression on adult ocular surface homeostasis. Methods. Binary Tet-On transgenic Krt12rtTA/tet-O-TGF-α mice were subjected to doxycycline (Dox) induction to overexpress TGF-α in the corneal epithelium. Intraocular pressure (IOP) was measured by noninvasive tonometry. The enucleated eyes of the experimental mice were subjected to histopathology, immunohistochemistry, and biochemistry examination. Results. Histologic and immunofluorescent examination showed that double-transgenic mice overexpressing TGF-α manifested peripheral anterior synechiae. Elevation of IOP, activation of glial cells, and loss of retinal ganglion cells were also observed. Quantitative real-time PCR revealed that the expressions of genes (RXRα, PITX2, and FOXC1) related to anterior segment dysgenesis were downregulated. Canonical Wnt signaling was suppressed, whereas noncanonical Wnt ligands (Wnt4 and Wnt5a) were upregulated. Increased myosin light chain phosphorylation suggested that noncanonical Wnt signaling is activated in affected eyes. Conclusions. Overexpression of TGF-α in the corneal epithelium induces changes in anterior segment morphology. Corneal endothelial abnormalities are associated with the activation of the noncanonical Wnt and RhoA/ROCK signaling axis, indicating a potential application of RhoA/ROCK inhibitors as a therapeutic strategy for certain types of secondary angle-closure glaucoma. PMID:23412089

  9. Intrastromal Corneal Ring Implants for Corneal Thinning Disorders

    PubMed Central

    2009-01-01

    refractive surgeons. It involves creating tunnels in the corneal stroma to secure the implants either by a diamond knife or laser calibrated to an approximate depth of 70% of the cornea. Variable approaches have been employed by surgeons in selecting ring segment size, number and position. Generally, two segments of equal thickness are placed superiorly and inferiorly to manage symmetrical patterns of corneal thinning whereas one segment may be placed to manage asymmetric thinning patterns. Following implantation, the major safety concerns are for potential adverse events including corneal perforation, infection, corneal infiltrates, corneal neovascularization, ring migration and extrusion and corneal thinning. Technical results can be unsatisfactory for several reasons. Treatment may result in an over or under-correction of refraction and may induce astigmatism or asymmetry of the cornea. Progression of the corneal cone with corneal opacities is also invariably an indication for progression to corneal transplant. Other reasons for treatment failure or patient dissatisfaction include foreign body sensation, unsatisfactory visual quality with symptoms such as double vision, fluctuating vision, poor night vision or visual side effects related to ring edge or induced or unresolved astigmatism. Evidence-Based Analysis Methods The literature search strategy employed keywords and subject headings to capture the concepts of 1) intrastromal corneal rings and 2) corneal diseases, with a focus on keratoconus, astigmatism, and corneal ectasia. The initial search was run on April 17, 2008, and a final search was run on March 6, 2009 in the following databases: Ovid MEDLINE (1996 to February Week 4 2009), OVID MEDLINE In-Process and Other Non-Indexed Citations, EMBASE (1980 to 2009 Week 10), OVID Cochrane Library, and the Centre for Reviews and Dissemination/International Agency for Health Technology Assessment. Parallel search strategies were developed for the remaining databases

  10. Excipients of preservative-free latanoprost induced inflammatory response and cytotoxicity in immortalized human HCE-2 corneal epithelial cells

    PubMed Central

    Smedowski, Adrian; Paterno, Jussi J.; Toropainen, Elisa; Sinha, Debasish; Wylegala, Edward; Kaarniranta, Kai

    2014-01-01

    Various preservative-free eye drop formulations for glaucoma treatment have been marketed intending to decrease ocular surface side effects and improve tolerability. However, preservative-free eye drops including different solubilizers to dissolve the antiglaucoma drugs may induce detrimental effects in the eye. In this study, we exposed human corneal epithelial cells (HCE-2) for 1, 6, 12, 24 and 48 hours to the first preservative-free (PF) tafluprost (Taflotan®), the recently-launched preservative-free (PF) latanoprost (Monoprost®), preservative benzalkonium chloride (BAK) and the excipient macrogolglycerol hydroxystearate 40 (MGHS40) using dilutions 0.1%, 0.3%, 1.0%, 3.0% and 10.0% of the original products. The cells also were exposed to undiluted PF tafluprost and PF latanoprost once a day for 9 days. Cellular morphology was examined by light microscopy and cell proliferation by Ki-67 fluorescent staining with cell viability being determined by erythrosine staining and the release of lactate dehydrogenase (LDH). Mitochondrial metabolic activity was evaluated with the colorimetric MTT assay. The secretion of interleukin 6 (IL-6) was measured with ELISA. HCE-2 cells displayed no significant morphological changes after PF tafluprost treatment, but PF latanoprost caused clear cell loss. Moreover, PF latanoprost, BAK and MGHS40 evoked cellular damage and inflammation with increasing concentrations and time. Furthermore, undiluted daily PF latanoprost application significantly increased LDH release and IL-6 secretion as compared to PF tafluprost. MGHS40 was observed to be associated with the toxicity of PF latanoprost. Excipients in ocular drops should receive more attention in the future, since they seem to trigger similar detrimental effects in cells as preservatives. PMID:25530926

  11. Fabricated or Induced Illness Presenting as Recurrent Corneal Lesions, Cataracts, and Uveitis.

    PubMed

    Valeina, Sandra; Krumina, Zita; Sepetiene, Svetlana; Andzane, Gunta; Sture, Elize Anna; Taylor, David

    2016-01-01

    Two siblings with ophthalmic findings, psychomotor retardation, somnolence, and seizures underwent diagnostic studies, genetic investigations, ultrasonography, biomicroscopy, and posterior and anterior optical coherence tomography. Both siblings experienced eye problems at different times from the age of 6 months to 12 years. The family pedigree and neurological problems (ie, hypotony, seizures, sleepiness, and speech and psychomotor delay) suggested a metabolic or mitochondrial pathology. After exclusion of multiple potential diseases, a fabricated or induced illness was suspected. Fabricated or induced illness can be a cause for unusual clinical findings and should be considered in the differential diagnosis when ocular and other abnormalities cannot be explained after a comprehensive evaluation. The diagnosis of fabricated or induced illness should not be based on exclusion alone but rather on positive findings. [J Pediatr Ophthalmol Strabismus. 2016;53:e6-e11.]. PMID:27007397

  12. Influence of corneal hydration on optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Twa, Michael D.; Vantipalli, Srilatha; Singh, Manmohan; Li, Jiasong; Larin, Kirill V.

    2016-03-01

    Corneal biomechanical properties are influenced by several factors, including intraocular pressure, corneal thickness, and viscoelastic responses. Corneal thickness is directly proportional to tissue hydration and can influence corneal stiffness, but there is no consensus on the magnitude or direction of this effect. We evaluated the influence of corneal hydration on dynamic surface deformation responses using optical coherence elastography (OCE). Fresh rabbit eyes (n=10) were prepared by removing the corneal epithelium and dropping with 0.9% saline every 5 minutes for 1 hour, followed by 20% dextran solution every 5 minutes for one hour. Corneal thickness was determined from structural OCT imaging and OCE measurements were performed at baseline and every 20 minutes thereafter. Micron-scale deformations were induced at the apex of the corneal tissue using a spatially-focused (150μm) short-duration (<1ms) air-pulse delivery system. These dynamic tissue responses were measured non-invasively with a phase-stabilized swept source OCT system. The tissue surface deformation response (Relaxation Rate: RR) was quantified as the time constant, over which stimulated tissue recovered from the maximum deformation amplitude. Elastic wave group velocity (GV) was also quantified and correlated with change in corneal thickness due to hydration process. Corneal thickness rapidly increased and remained constant following epithelium removal and changed little thereafter. Likewise, corneal stiffness changed little over the first hour and then decreased sharply after Dextran application (thickness: -46% [-315/682 μm] RR: - 24% [-0.7/2.88 ms-1]; GV: -19% [-0.6/3.2 m/s]). Corneal thickness and corneal stiffness (RR) were well correlated (R2 = .66). Corneal biomechanical properties are highly correlated with tissue hydration over a wide range of corneal thickness and these changes in corneal stiffness are quantifiable using OCE.

  13. The phacoemulsification procedure. II. Corneal endothelial changes.

    PubMed

    Polack, F M; Sugar, A

    1976-06-01

    The effect of phacoemulsification, with the Cavitron-Kelman instrument, on the corneal endothelium of rabbit and cats was studied by scanning electron microscopy and nitroblue tetrazolium staining. The various steps of the procedure were examined separately. Irrigation of the anterior chamber of the eye with balanced salt solution (Plasma-Lyte) for ten minutes caused no cell damage. Ultrasound and irrigation alone for four to six minutes caused increased permeability to NBT. Edema of endothelial cells and cell junction disruption occurred after eight minutes of anterior chamber irrigation with Plasma-Lyte. Uncomplicated phacoemulsification produced moderate cellular edema with scattered loss of endothelial cells. Destruction of endothelial cells was frequent after phacoemulsification, it appeared to be due to lens nucleus manipulation in the anterior chamber, instrumentation, and needle contact. From two to five days postoperatively, intercellular edema, altered cell morphology, and mosaic pattern were seen. However, it gradually recovered and seven to ten days later the endothelium appeared normal. PMID:931690

  14. Atrial natriuretic peptide attenuates agonist-induced pulmonary edema in mice with targeted disruption of the gene for natriuretic peptide receptor-A

    PubMed Central

    Tsai, Shu-Whei; Green, Sabrina; Grinnell, Katie L.; Machan, Jason T.; Harrington, Elizabeth O.

    2013-01-01

    Atrial natriuretic peptide (ANP) inhibits agonist-induced pulmonary edema formation, but the signaling pathway responsible is not well defined. To investigate the role of the particulate guanylate cyclase-linked receptor, natriuretic peptide receptor-A (NPR-A), we measured acute lung injury responses in intact mice and pulmonary microvascular endothelial cells (PMVEC) with normal and disrupted expression of NPR-A. NPR-A wild-type (NPR-A+/+), heterozygous (NPR-A+/−), and knockout (NPR-A−/−) mice were anesthetized and treated with thrombin receptor agonist peptide (TRAP) or lipopolysaccharide (LPS). Lung injury was assessed by lung wet-to-dry (W/D) weight and by protein and cell concentration of bronchoalveolar lavage (BAL) fluid. No difference in pulmonary edema formation was seen between NPR-A genotypes under baseline conditions. TRAP and LPS increased lung W/D weight and BAL fluid cell counts more in NPR-A−/− mice than in NPR-A+/− or NPR-A+/+ mice, but no genotype-related differences were seen in TRAP-induced increases in bloodless lung W/D weight or LPS-induced increases in BAL protein concentration. Pretreatment with ANP infusion completely blocked TRAP-induced increases in lung W/D weight and blunted LPS-induced increases in BAL cell counts and protein concentration in both NPR-A−/− and NPR-A+/+ mice. Thrombin decreased transmembrane electrical resistance in monolayers of PMVECs in vitro, and this effect was attenuated by ANP in PMVECs isolated from both genotypes. Administration of the NPR-C-specific ligand, cANF, also blocked TRAP-induced increases in lung W/D weight and LPS-induced increases in BAL cell count and protein concentration in NPR-A+/+ and NPR-A−/− mice. We conclude that ANP is capable of attenuating agonist-induced lung edema in the absence of NPR-A. The protective effect of ANP on agonist-induced lung injury and pulmonary barrier function may be mediated by NPR-C. PMID:23195629

  15. Atrial natriuretic peptide attenuates agonist-induced pulmonary edema in mice with targeted disruption of the gene for natriuretic peptide receptor-A.

    PubMed

    Klinger, James R; Tsai, Shu-Whei; Green, Sabrina; Grinnell, Katie L; Machan, Jason T; Harrington, Elizabeth O

    2013-02-01

    Atrial natriuretic peptide (ANP) inhibits agonist-induced pulmonary edema formation, but the signaling pathway responsible is not well defined. To investigate the role of the particulate guanylate cyclase-linked receptor, natriuretic peptide receptor-A (NPR-A), we measured acute lung injury responses in intact mice and pulmonary microvascular endothelial cells (PMVEC) with normal and disrupted expression of NPR-A. NPR-A wild-type (NPR-A+/+), heterozygous (NPR-A+/-), and knockout (NPR-A-/-) mice were anesthetized and treated with thrombin receptor agonist peptide (TRAP) or lipopolysaccharide (LPS). Lung injury was assessed by lung wet-to-dry (W/D) weight and by protein and cell concentration of bronchoalveolar lavage (BAL) fluid. No difference in pulmonary edema formation was seen between NPR-A genotypes under baseline conditions. TRAP and LPS increased lung W/D weight and BAL fluid cell counts more in NPR-A-/- mice than in NPR-A+/- or NPR-A+/+ mice, but no genotype-related differences were seen in TRAP-induced increases in bloodless lung W/D weight or LPS-induced increases in BAL protein concentration. Pretreatment with ANP infusion completely blocked TRAP-induced increases in lung W/D weight and blunted LPS-induced increases in BAL cell counts and protein concentration in both NPR-A-/- and NPR-A+/+ mice. Thrombin decreased transmembrane electrical resistance in monolayers of PMVECs in vitro, and this effect was attenuated by ANP in PMVECs isolated from both genotypes. Administration of the NPR-C-specific ligand, cANF, also blocked TRAP-induced increases in lung W/D weight and LPS-induced increases in BAL cell count and protein concentration in NPR-A+/+ and NPR-A-/- mice. We conclude that ANP is capable of attenuating agonist-induced lung edema in the absence of NPR-A. The protective effect of ANP on agonist-induced lung injury and pulmonary barrier function may be mediated by NPR-C. PMID:23195629

  16. Thrombomodulin Promotes Corneal Epithelial Wound Healing

    PubMed Central

    Huang, Yi-Hsun; I, Ching-Chang; Kuo, Cheng-Hsiang; Hsu, Yun-Yan; Lee, Fang-Tzu; Shi, Guey-Yueh; Tseng, Sung-Huei; Wu, Hua-Lin

    2015-01-01

    Purpose To determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23) has therapeutic potential in corneal epithelial wound healing. Methods TM localization and expression in the murine cornea were examined by immunofluorescence staining. TM expression after injury was also studied. The effect of rTMD23 on corneal wound healing was evaluated by in vitro and in vivo assays. Results TM was expressed in the cornea in normal adult mice. TM expression increased in the early phase of wound healing and decreased after wound recovery. In the in vitro study, platelet-derived growth factor-BB (PDGF-BB) induced TM expression in murine corneal epithelial cells by mediating E26 transformation-specific sequence-1 (Ets-1) via the mammalian target of rapamycin (mTOR) signaling pathway. The administration of rTMD23 increased the rate of corneal epithelial wound healing. Conclusions TM expression in corneal epithelium was modulated during the corneal wound healing process, and may be regulated by PDGF-BB. In addition, rTMD23 has therapeutic potential in corneal injury. PMID:25816372

  17. Corneal Abrasions and Corneal Foreign Bodies.

    PubMed

    Ahmed, Faheem; House, Robert James; Feldman, Brad Hal

    2015-09-01

    Corneal abrasions and corneal foreign bodies are frequently encountered ophthalmological injuries that are commonly diagnosed and managed by primary care physicians. The clinical course of a corneal epithelial defect can range from a relatively benign self-healing abrasion to a potentially sight-threatening complication such as a corneal ulcer, recurrent erosion, or traumatic iritis. A detailed clinical history regarding risk factors and exposure, along with a thorough slit lamp examination with fluorescein dye are essential for proper diagnosis and treatment, as well as to rule out penetrating globe injuries. Referral to an ophthalmologist is recommended in difficult cases or if other injuries are suspected. PMID:26319343

  18. Corneal temperature in schizophrenia patients.

    PubMed

    Shiloh, Roni; Munitz, Hanan; Portuguese, Shirley; Gross-Isseroff, Ruth; Sigler, Mayanit; Bodinger, Liron; Katz, Nachum; Stryjer, Rafael; Hermesh, Haggai; Weizman, Abraham

    2005-12-01

    Most data imply that dopaminergic transmission is essential for proper hypothalamic-mediated core temperature regulation. Altered central dopaminergic transmission is suggested to be involved in the pathophysiology of schizophrenia. Thus, hypothetically, schizophrenia patients might be at increased risk of developing thermoregulatory dysregulation manifested by alterations in core temperature, as well as in peripheral tissue, the temperature of which has been shown to correlate with core temperature (e.g. cornea). Previous small pilot studies of ours showed that schizophrenia patients may exhibit corneal temperature abnormalities. Hence, we assessed corneal temperature in a controlled sample of drug-free ( n =11) and medicated ( n =28) schizophrenia patients compared to healthy comparison subjects ( n =9), using a FLIR thermal imaging camera. Drug-free schizophrenia patients exhibited significantly higher corneal temperature compared to healthy subjects, typical antipsychotic drug (APD)-treated patients ( n =16) and atypical APD-treated patients ( n =12) (37.08+/-1.46 degrees C vs. 33.37+/-2.51 degrees C, 31.08+/-1.43 degrees C and 31.67+/-0.44 degrees C respectively, p <0.0001; p <0.001 vs. each group separately). The healthy comparison subjects and the atypical APD-treated patients exhibited comparable corneal temperatures and these two groups exhibited higher corneal temperatures compared to the typical APD-treated patients ( p <0.01 and p =0.051 respectively). In conclusion, this study indicates that drug-free schizophrenia patients exhibit substantially higher corneal temperature compared to healthy comparison subjects or medicated patients, and that APDs may decrease corneal temperature either to normal (atypical APD) or to subnormal (typical APD) values. The relevance of these phenomena to the pathophysiology of schizophrenia, the biological mechanism underlying drug-induced corneal temperature alterations, the possible role of temperature-lowering drugs

  19. Outcome of Two Corneal Collagen Crosslinking Methods in Bullous Keratopathy due to Fuchs' Endothelial Dystrophy.

    PubMed

    Ucakhan, Omur O; Saglik, Ayhan

    2014-01-01

    Four eyes of 2 patients with corneal edema due to Fuchs' endothelial dystrophy were treated with CXL using the standard protocol. Since no improvement in visual acuity, corneal clarity, thickness, or pain sensation was evident in any eye at month 12, 2 eyes of the 2 patients were retreated, this time, following intraoperative corneal dehydration with glycerol 70% drops. This retreatment also failed to produce any significant effect on vision, corneal clarity, thickness, or pain in either eye. Collagen crosslinking with the current protocols may not be effective in the management of eyes with corneal edema due to Fuchs' endothelial dystrophy. Further studies are required to establish the efficacy of CXL and optimize the technique and/or dehydration method utilized in these cases. PMID:25484904

  20. Corneal Foreign Body

    MedlinePlus

    ... Care Guidelines As with corneal abrasions and recurrent erosion of the cornea, self-care includes: Never rubbing ... can be found about corneal abrasions and recurrent erosion of the cornea in their respective diagnoses. When ...

  1. Post DSAEK Optical Changes: A Comprehensive Prospective Analysis on the Role of Ocular Wavefront Aberrations, Haze, and Corneal Thickness

    PubMed Central

    Hindman, Holly B.; Huxlin, Krystel R.; Pantanelli, Seth M.; Callan, Christine L.; Sabesan, Ramkumar; Ching, Steven S.T.; Miller, Brooke E.; Martin, Tim; Yoon, Geunyoung

    2014-01-01

    Purpose To assess the visual impact of ocular wavefront aberrations, corneal thickness, and corneal light scatter prospectively after Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK) in humans. Methods Data were obtained prospectively from 20 eyes pre-operatively and at 1, 3, 6, and 12 months post- DSAEK. At each visit, best spectacle corrected visual acuity (BSCVA) and visual acuity with glare (Brightness Acuity Testing - BAT) were recorded and ocular wavefront measurements and corneal Optical Coherence Tomography (OCT) performed. Magnitude and sign of individual Zernike terms (higher order aberrations HOA) were determined. Epithelial, host stromal, donor stromal, and total corneal thickness were quantified. Brightness, intensity profiles of OCT images were generated to quantify light scatter in the whole cornea, subepithelial region, anterior and posterior host stroma, interface, and donor stroma. Results Mean BSCVA and glare disability at low light levels improved from 1 to 12 months post-DSAEK. All corneal thicknesses and ocular lower- and HOAs were stable from 1 through 12 months, whereas total corneal, host stromal, and interface brightness intensities decreased significantly over the same period. A repeated measures ANOVA across the follow up period found that the change in scatter, but not the change in higher order aberrations, could account for the variability occurring in acuity from 1 to 12 months post-DSAEK. Conclusions While ocular HOAs and scatter are both elevated over normal post-DSAEK, our results demonstrate that improvements in visual performance occurring over the first year post-DSAEK are associated with decreasing light scatter. In contrast, there were no significant changes in ocular HOAs during this time. Because corneal light scatter decreased between 1 and 12 months despite stable corneal thicknesses over the same period, we conclude that factors that induced light scatter, other than tissue thickness or swelling (corneal

  2. A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats

    PubMed Central

    Mansouri, Mohammad Taghi; Hemmati, Ali Asghar; Naghizadeh, Bahareh; Mard, Seyyed Ali; Rezaie, Anahita; Ghorbanzadeh, Behnam

    2015-01-01

    Objectives: Ellagic acid (EA) has shown antinociceptive and anti-inflammatory effects. Inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) enzymes and also cytokines play a key role in many inflammatory conditions. This study was aimed to investigate the mechanisms involved in the anti-inflammatory effect of EA. Materials and Methods: Carrageenan-induced mouse paw edema model was used for induction of inflammation. Results: The results showed that intraplantar injection of carrageenan led to time-dependent development of peripheral inflammation, which resulted in a significant increase in the levels of tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) β, nitric oxide (NO) and prostaglandin E2 (PGE2) and also iNOS and COX-2 protein expression in inflamed paw. However, systemic administration of EA (1–30 mg/kg, intraperitoneal [i.p.]) could reduce edema in a dose-dependent fashion in inflamed rat paws with ED50 value 8.41 (5.26–14.76) mg/kg. It decreased the serum concentration of NO, PGE2, aspartate aminotransferase and alanine aminotransferase, and suppress the protein expression of iNOS, COX-2 enzymes, and attenuated the formation of PGE2, TNF-α and IL-1 β in inflamed paw tissue. We also demonstrated that EA significantly decreased the malondialdehyde (MDA) level in liver at 5 h after carrageenan injection. Moreover, histopathological studies indicated that EA significantly diminished migration of polymorphonuclear leukocytes into site of inflammation, as did indomethacin. Conclusions: Collectively, the anti-inflammatory mechanisms of EA might be related to the decrease in the level of MDA, iNOS, and COX-2 in the edema paw via the suppression of pro-inflammatory cytokines (TNFα, IL1 β), NO and PGE2 overproduction. PMID:26069367

  3. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    SciTech Connect

    Arab, Hany H.; El-Sawalhi, Maha M.

    2013-04-15

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of

  4. Analysis of gene regulation in rabbit corneal epithelial cells induced by ultraviolet radiation.

    PubMed

    Stevens, Jacqueline J; Rogers, Christian; Howard, Carolyn B; Moore, Caronda; Chan, Lai-Man

    2005-04-01

    Ultraviolet (UV)-induced cataracts are becoming a major environmental health concern because of the possible decrease in the stratospheric ozone layer. Experiments were designed to isolate gene(s) affected by UV irradiation in rabbit cornea tissues using fluorescent differential display-reverse transcription-polymerase chain reaction (FDDRT-PCR). The epithelial cells were grown in standard medium for 2 or 4 hours post treatment. Cornea epithelial cells were irradiated with UVB for 20 minutes. RNA was extracted and amplified by reverse transcriptase-polymerase chain reaction using poly A+ specific anchoring primers and random arbitrary primers. Polyacrylamide gel electrophoresis revealed several differentially expressed genes in untreated versus UV irradiated cells. Complimentary DNA (cDNA) fragments resulting from fluorescent differentially expressed mRNAs were eluted from the gel and re-amplified. The re-amplified PCR products were cloned directly into the PCR-TRAP cloning system. These data showed that FDDRT-PCR is a useful technique to elucidate UV-regulated gene expressions. Future experiments will involve sequence analysis of cloned inserts. The identification of these genes through sequence analysis could lead to a better understanding of cataract formation via DNA damage and mechanisms of prevention. PMID:16705801

  5. Progress in corneal wound healing.

    PubMed

    Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2015-11-01

    Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal

  6. Sulforaphane Decreases Endothelial Cell Apoptosis in Fuchs Endothelial Corneal Dystrophy: A Novel Treatment

    PubMed Central

    Ziaei, Alireza; Schmedt, Thore; Chen, Yuming; Jurkunas, Ula V.

    2013-01-01

    Purpose. Fuchs endothelial corneal dystrophy (FECD) is an oxidative stress disorder that leads to age-related and gradual loss of corneal endothelial cells resulting in corneal edema and loss of vision. To date, other than surgical intervention, there are no treatment options for patients with FECD. We have shown that in FECD, there is a deficiency in nuclear factor erythroid 2-related factor 2 (Nrf2)–regulated antioxidant defense due to decreased Nrf2 nuclear translocation and activation of antioxidant response element (ARE). In this study, we used sulforaphane (SFN) and D3T to investigate a strategy of targeting Nrf2-ARE in FECD. Methods. FECD and normal ex vivo corneas and human corneal endothelial cell lines were pretreated with SFN or D3T and exposed to oxidative stress with tert-Butyl hydroperoxide (tBHP). Apoptosis was detected with TUNEL. Cellular localization of Nrf2 and p53 was assessed by immunohistochemistry. Effect of SFN was determined by using DCFDA assay, Western blot and real-time PCR. Results. After pretreatment with SFN, oxidative stress was induced with tBHP. In ex vivo FECD specimens, SFN decreased CEC apoptosis by 55% in unstressed group and by 43% in tBHP-treated specimens. SFN enhanced nuclear translocation of Nrf2 in FECD specimens and decreased p53 staining under oxidative stress. Pretreatment with SFN enhanced cell viability by decreasing intracellular reactive oxygen species production. Upregulation of Nrf2 levels led to increased synthesis of DJ-1, heme oxygenase 1, and nicotinamide adenine dinucleotide quinone oxidoreductase-1. SFN significantly upregulated major ARE-dependent antioxidants and ameliorated oxidative stress–induced apoptosis in FECD. Conclusions. Our results suggest that targeting Nrf2-ARE pathway may arrest degenerative cell loss seen in FECD. PMID:24030461

  7. Release-active dilutions of diclofenac enhance anti-inflammatory effect of diclofenac in carrageenan-induced rat paw edema model.

    PubMed

    Sakat, Sachin S; Mani, Kamaraj; Demidchenko, Yulia O; Gorbunov, Evgeniy A; Tarasov, Sergey A; Mathur, Archna; Epstein, Oleg I

    2014-02-01

    The study was aimed to investigate the effect of technologically treated diclofenac (release-active dilutions of diclofenac (RAD of diclofenac)) on anti-inflammatory activity of diclofenac in carrageenan-induced rat paw edema model. Ninety male Wistar albino rats (6-8 weeks) divided into nine groups (n = 10) were used. Anti-inflammatory activity was assessed at 1, 2, 3, 4, and 6 h after subplantar injection of carrageenan (0.1 ml of a 1 % solution in normal saline). Diclofenac alone was studied at 5 and 20 mg/kg, RAD of diclofenac alone at 7.5 ml/kg and their combination at 5 and 7.5 ml/kg, respectively. Diclofenac reduced (p < 0.05 at least) paw edema at all time points. RAD of diclofenac enhanced (p < 0.05) anti-inflammatory effect of diclofenac (5 mg/kg) at 2, 4, and 6 h on concurrent and at 2 and 4 h on sequential administration. Moreover at 2 h, anti-inflammatory effect of combination treatment reached values comparable to those of diclofenac (20 mg/kg). In conclusion, RAD of diclofenac enhanced anti-inflammatory effect of diclofenac. PMID:24005897

  8. Research on mouse model of grade II corneal alkali burn

    PubMed Central

    Bai, Jun-Qiang; Qin, Hai-Feng; Zhao, Shi-Hong

    2016-01-01

    AIM To choose appropriate concentration of sodium hydroxide (NaOH) solution to establish a stable and consistent corneal alkali burn mouse model in grade II. METHODS The mice (n=60) were randomly divided into four groups and 15 mice each group. Corneal alkali burns were induced by placing circle filter paper soaked with NaOH solutions on the right central cornea for 30s. The concentrations of NaOH solutions of groups A, B, C, and D were 0.1 mol/L, 0.15 mol/L, 0.2 mol/L, and 1.0 mol/L respectively. Then these corneas were irrigated with 20 mL physiological saline (0.9% NaCl). On day 7 postburn, slit lamp microscope was used to observe corneal opacity, corneal epithelial sodium fluorescein staining positive rate, incidence of corneal ulcer and corneal neovascularization, meanwhile pictures of the anterior eyes were taken. Cirrus spectral domain optical coherence tomography was used to scan cornea to observe corneal epithelial defect and corneal ulcer. RESULTS Corneal opacity scores (x±s) were not significantly different between the group A and group B (P=0.097). Incidence of corneal ulcer in group B was significantly higher than that in group A (P=0.035). Incidence of corneal ulcer and perforation rate in group B was lower than that in group C. Group C and D had corneal neovascularization, and incidence of corneal neovascularization in group D was significantly higher than that in group C (P=0.000). CONCLUSION Using 0.15 mol/L NaOH can establish grade II mouse model of corneal alkali burns. PMID:27162717

  9. Novel insights into phosgene-induced acute lung injury in rats: role of dysregulated cardiopulmonary reflexes and nitric oxide in lung edema pathogenesis.

    PubMed

    Li, Wenli; Liu, Fangfang; Wang, Chen; Truebel, Hubert; Pauluhn, Juergen

    2013-02-01

    Phosgene gas is a lower respiratory tract irritant. As such, it stimulates nociceptive vagal C-fiber-related reflexes in a dose-rate and concentration × exposure duration (C × t)-dependent manner. In rats, this reflex is characterized by extended apnea time periods, bradycardia, and hypothermia. Although inhalation exposures at nonlethal C × t products show rapid reversibility of reflexively induced changes in respiratory patterns, lethal C × t products seem to cause prolonged stimulation after discontinued exposure to phosgene. This observation has been taken as indirect evidence that phosgene-induced lethal lung edema is likely to be associated with a dysfunctional neurogenic control of cardiopulmonary and microvascular physiology. In order to verify this hypothesis, data from respiratory function measurements during and after the inhalation exposure to phosgene gas were compared with time-course measurements of cardiac function over 20 h post-phosgene exposure. These data were complemented by time-course analyses of nitric oxide (NO(e)) and carbon dioxide in exhaled breath, including time-dependent changes of extravasated protein in bronchoalveolar lavage fluid and hemoglobin in blood. The nitric oxidase synthetase inhibitors L-NAME and L-NIL were used to further elucidate the role of NO(e) in this type of acute lung injury and whether its analysis can serve as an early biomarker of pulmonary injury. Collectively, the sequence and time course of pathological events in phosgene-induced lung edema appear to suggest that overstimulated, continued sensorimotor vagal reflexes affect cardiopulmonary hemodynamics. A continued parasympathetic tone appears to be involved in this etiopathology. PMID:23143928

  10. Molecular mechanisms of dust-induced toxicity in human corneal epithelial cells: Water and organic extract of office and house dust.

    PubMed

    Xiang, Ping; Liu, Rong-Yan; Sun, Hong-Jie; Han, Yong-He; He, Rui-Wen; Cui, Xin-Yi; Ma, Lena Q

    2016-01-01

    Human corneal epithelial (HCE) cells are continually exposed to dust in the air, which may cause corneal epithelium damage. Both water and organic soluble contaminants in dust may contribute to cytotoxicity in HCE cells, however, the associated toxicity mechanisms are not fully elucidated. In this study, indoor dust from residential houses and commercial offices in Nanjing, China was collected and the effects of organic and water soluble fraction of dust on primary HCE cells were examined. The concentrations of heavy metals in the dust and dust extracts were determined by ICP-MS and PAHs by GC-MS, with office dust having greater concentrations of heavy metals and PAHs than house dust. Based on LC50, organic extract was more toxic than water extract, and office dust was more toxic than house dust. Accordingly, the organic extracts induced more ROS, malondialdehyde, and 8-Hydroxydeoxyguanosine and higher expression of inflammatory mediators (IL-1β, IL-6, and IL-8), and AhR inducible genes (CYP1A1, and CYP1B1) than water extracts (p<0.05). Extracts of office dust presented greater suppression of superoxide dismutase and catalase activity than those of house dust. In addition, exposure to dust extracts activated NF-κB signal pathway except water extract of house dust. The results suggested that both water and organic soluble fractions of dust caused cytotoxicity, oxidative damage, inflammatory response, and activation of AhR inducible genes, with organic extracts having higher potential to induce adverse effects on primary HCE cells. The results based on primary HCE cells demonstrated the importance of reducing contaminants in indoor dust to reduce their adverse impacts on human eyes. PMID:27131017

  11. Evidence against a blood derived origin for transforming growth factor beta induced protein in corneal disorders caused by mutations in the TGFBI gene

    PubMed Central

    Karring, Henrik; Valnickova, Zuzana; Thøgersen, Ida B.; Hedegaard, Chris J.; Møller-Pedersen, Torben; Kristensen, Torsten; Klintworth, Gordon K.

    2007-01-01

    Purpose Several inherited corneal disorders in humans result from mutations in the transforming growth factor beta induced gene (TGFBI), which encodes for the extracellular transforming growth factor beta induced protein (TGFBIp) that is one of the most abundant proteins in the cornea. We previously reported a significant amount of TGFBIp in plasma by immunoblotting using the only TGFBIp antiserum (anti-p68βig-h3) available at that time (anti-p68βig-h3 was generated against residues Val210-His683 of TGFBIp). This observation raised the possibility that a fraction of corneal TGFBIp may originate from the plasma. However, recent experiments in our laboratory indicated that the anti-p68βig-h3 antiserum cross-reacts with an environmental protein contaminant. Therefore, we investigated the specificity of the originally utilized anti-p68βig-h3 antiserum and re-evaluated the amount of TGFBIp in human plasma by immunoblotting using a new specific antiserum. Methods The observed cross-reactivity of the previously utilized anti-p68βig-h3 antiserum was tested by immunoblotting and the antigen identity was determined by mass spectrometry. A part of human TGFBI encoding an NH2-terminal 11.4 kDa fragment of TGFBIp (residues Gly134-Ile236) was amplified by polymerase chain reaction (PCR) and cloned in E. coli. The TGFBIp fragment was expressed in E. coli, purified by Ni2+-affinity chromatography, and used to immunize rabbits to produce a specific antiserum (anti-TGFBIp134-236). To enhance the detection of possible TGFBIp in plasma by allowing a higher sample load, albumin and immunoglobulin G (IgG) were specifically depleted from normal human plasma by affinity chromatography. The presence of TGFBIp in plasma was investigated by immunoblotting using the anti-TGFBIp134-236 antiserum. Purified TGFBIp from porcine corneas was used for estimation of the TGFBIp detection limit. Results The previously utilized TGFBIp antiserum, anti-p68βig-h3, cross-reacted with human keratin-1

  12. Clear Corneal Incision in Cataract Surgery

    PubMed Central

    Al Mahmood, Ammar M.; Al-Swailem, Samar A.; Behrens, Ashley

    2014-01-01

    Since the introduction of sutureless clear corneal cataract incisions, the procedure has gained increasing popularity worldwide because it offers several advantages over the traditional sutured scleral tunnels and limbal incisions. Some of these benefits include lack of conjunctival trauma, less discomfort and bleeding, absence of suture-induced astigmatism, and faster visual rehabilitation. However, an increasing incidence of postoperative endophthalmitis after clear corneal cataract surgery has been reported. Different authors have shown a significant increase up to 15-fold in the incidence of endophthalmitis following clear corneal incision compared to scleral tunnels. The aim of this report is to review the advantages and disadvantages of clear corneal incisions in cataract surgery, emphasizing on wound construction recommendations based on published literature. PMID:24669142

  13. Clear corneal incision in cataract surgery.

    PubMed

    Al Mahmood, Ammar M; Al-Swailem, Samar A; Behrens, Ashley

    2014-01-01

    Since the introduction of sutureless clear corneal cataract incisions, the procedure has gained increasing popularity worldwide because it offers several advantages over the traditional sutured scleral tunnels and limbal incisions. Some of these benefits include lack of conjunctival trauma, less discomfort and bleeding, absence of suture-induced astigmatism, and faster visual rehabilitation. However, an increasing incidence of postoperative endophthalmitis after clear corneal cataract surgery has been reported. Different authors have shown a significant increase up to 15-fold in the incidence of endophthalmitis following clear corneal incision compared to scleral tunnels. The aim of this report is to review the advantages and disadvantages of clear corneal incisions in cataract surgery, emphasizing on wound construction recommendations based on published literature. PMID:24669142

  14. Positional accommodative intraocular lens power error induced by the estimation of the corneal power and the effective lens position

    PubMed Central

    Piñero, David P; Camps, Vicente J; Ramón, María L; Mateo, Verónica; Pérez-Cambrodí, Rafael J

    2015-01-01

    Purpose: To evaluate the predictability of the refractive correction achieved with a positional accommodating intraocular lenses (IOL) and to develop a potential optimization of it by minimizing the error associated with the keratometric estimation of the corneal power and by developing a predictive formula for the effective lens position (ELP). Materials and Methods: Clinical data from 25 eyes of 14 patients (age range, 52–77 years) and undergoing cataract surgery with implantation of the accommodating IOL Crystalens HD (Bausch and Lomb) were retrospectively reviewed. In all cases, the calculation of an adjusted IOL power (PIOLadj) based on Gaussian optics considering the residual refractive error was done using a variable keratometric index value (nkadj) for corneal power estimation with and without using an estimation algorithm for ELP obtained by multiple regression analysis (ELPadj). PIOLadj was compared to the real IOL power implanted (PIOLReal, calculated with the SRK-T formula) and also to the values estimated by the Haigis, HofferQ, and Holladay I formulas. Results: No statistically significant differences were found between PIOLReal and PIOLadj when ELPadj was used (P = 0.10), with a range of agreement between calculations of 1.23 D. In contrast, PIOLReal was significantly higher when compared to PIOLadj without using ELPadj and also compared to the values estimated by the other formulas. Conclusions: Predictable refractive outcomes can be obtained with the accommodating IOL Crystalens HD using a variable keratometric index for corneal power estimation and by estimating ELP with an algorithm dependent on anatomical factors and age. PMID:26139807

  15. Cytotoxicity of carteolol to human corneal epithelial cells by inducing apoptosis via triggering the Bcl-2 family protein-mediated mitochondrial pro-apoptotic pathway.

    PubMed

    Shan, Ming; Fan, Ting-Jun

    2016-09-01

    Carteolol is a frequently used nonselective β-adrenoceptor antagonist for glaucoma and ocular hypertension treatment, and its repeated/prolonged usage might be cytotoxic to the cornea, especially the outmost human corneal epithelium (HCEP). The aim of the present study was to characterize the cytotoxicity of carteolol to HCEP and its underlying cellular and molecular mechanisms using an in vitro model of HCEP cells. After HCEP cells were treated with carteolol at concentrations varying from 2% to 0.015625%, the cytotoxicity, apoptosis-inducing effect and pro-apoptotic pathway was investigated, respectively. Our results showed that carteolol at concentrations above 0.03125% induced time- and dose-dependent growth retardation, cytopathic morphological changes and viability decline of HCEP cells. Moreover, carteolol induced G1 phase arrest, plasma membrane permeability elevation, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation of HCEP cells. Furthermore, carteolol also induced activation of caspase-9 and -3, disruption of mitochondrial transmembrane potential, up-regulation the cytoplasmic amount of cytochrome c and apoptosis-inducing factor, and up-regulation of pro-apoptotic Bax and Bad, down-regulation of anti-apoptotic Bcl-2 and Bcl-xL. In conclusion, carteolol above 1/64 of its clinical therapeutic dosage has a time- and dose-dependent cytotoxicity to HCEP cells, which is achieved by inducing apoptosis via triggering Bcl-2 family protein-mediated mitochondrial pro-apoptotic pathway. PMID:27216471

  16. Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants - a bio-mathematical model

    NASA Astrophysics Data System (ADS)

    Yue, Ning; Chen, Zhe; Nath, Ravinder

    2002-04-01

    Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both 125I and 103Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T) = Vp (1 + M exp(-0.693T/Te)) where Vp is the prostate volume before implantation, M is the edema magnitude and Te is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. Λg(r) αBED), where α is the linear coefficient of the survival curve. The tumour cell survival was calculated for both 125I and 103Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days and a magnitude of 50%, the edema increased tumour cell survival by about 1 and 2 orders of magnitude for 125I and 103Pd seed implants respectively. At the extreme (95% edema magnitude and an edema half-life of 30 days), the increase was more than 3 and 5 orders of magnitude for 125I and 103Pd seed implants respectively. The absolute increases were almost independent of TPDT and the prostate edema did not significantly change the effective treatment time. Tumour cell survival for prostate undergoing CLDRI using 125I or 103Pd seeds may be increased substantially due to the presence of edema caused by surgical trauma. This effect appears to be more pronounced for

  17. Clinical correlates of common corneal neovascular diseases: a literature review

    PubMed Central

    Abdelfattah, Nizar Saleh; Amgad, Mohamed; Zayed, Amira A; Salem, Hamdy; Elkhanany, Ahmed E; Hussein, Heba; Abd El-Baky, Nawal

    2015-01-01

    A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far. PMID:25709930

  18. Effect of melengestrol acetate on development of 3-methylindole-induced pulmonary edema and emphysema in sheep.

    PubMed Central

    Popp, J D; McAllister, T A; Kastelic, J P; Majak, W; Ayroud, M; VanderKop, M A; Karren, D; Yost, G S; Cheng, K J

    1998-01-01

    The involvement of melengestrol acetate (MGA) in susceptibility to developing pulmonary edema and emphysema following oral administration of 3-methylindole (3MI) was investigated using 10 Suffolk ewes receiving 0 or 0.15 mg of MGA daily (n = 5). Blood, urine and ruminal fluid were collected immediately prior to 3MI dosing (0.2 g/kg BW) and 1, 2, 3, 4, 5, 6, 12 and 24 h (blood); 3, 6, 9, 12 and 15 h (urine) and 1, 2, 3 and 12 h (ruminal fluid) afterward. Ewes receiving MGA experienced earlier (P < 0.05) onset of respiratory distress than the control ewes (2.5 vs 4 h), and upon euthanasia at 96 h, their lung weight relative to body weight tended (P < 0.10) to be lower. Ruminal 3MI concentrations did not differ between treatments (P > 0.05). Ewes receiving MGA had higher (P < 0.05) concentrations of 3MI metabolites in plasma prior to dosing than did control ewes, and these values tended to remain higher throughout the sampling period. Immunoreactivity assays indicated more pneumotoxin present in the lungs of MGA-treated ewes than controls. Lung damage was apparently more acute and accelerated in the MGA-treated ewes than in the controls. Urinary 3MI mercapturate concentrations differed (control > MGA-treated, P < 0.05) at 9, 12, and 15 h, but this difference was not apparent when urinary production (as estimated by creatinine concentration) was considered. The implications of these findings for MGA-treated feedlot heifers are currently under investigation. Images Figure 1. PMID:9798092

  19. Purification and inflammatory edema induced by two PLA2 (Anch TX-I and Anch TX-II) from sea anemone Anthothoe chilensis (Actiniaria: Sagartiidae).

    PubMed

    Landucci, Elen Cristina Teizem; Dias, Queila Cristina; Marangoni, Fábio André; Vilca-Quispe, Augusto; Valeriano-Zapana, José Antonio; Torres-Huaco, Frank Denis; Martins-de-Souza, Daniel; Marangoni, Sergio; Ponce-Soto, Luis Alberto

    2012-02-01

    The Anch TX-I and II PLA(2) were purified from Anthothoe chilensis (Lesson, 1830) from the extract of the anemone after only two chromatographic step using molecular exclusion chromatography (Sephadex G-75) and reverse phase HPLC on μ-Bondapak C18 column. Both PLA(2) showed a molecular mass of ~14kDa determined by MALDI-TOF mass spectrometry and showed a high catalytic activity (data not showed). Although homologous with mammalian or snake venom group I PLA(2)s, Anch TX-I and II is sufficiently structurally different for the question of its placement into the existing PLA(2) classification scheme to arise. In addition, Anch TX-I and II, despite possessing many common structural features, also differ in some important structural properties. The amino acid sequence of both PLA(2) (Anch TX-I and III) showed high amino acid sequence identity with PLA(2)Rhopilema nomadica and Bunodosoma caissarum Cnidaria and PLA(2) of group III protein isolated from the Mexican lizard Heloderma horridum horridum and Heloderma suspectum. In addition, Anch TX-I and Anch TX-II showed high amino acid sequence identity with PLA(2) from group III also showed significant overall homology to bee Apis dorsata, Bombus terrestris and Bombus pennsylvanicus and PLA(2). We also investigated the in vivo edematogenic activity of Anch TX-I and Anch TX-II in a model of paw and skin edema in rats and observed that both are able to induce dose-dependent edema. PMID:22100907

  20. Delayed Corneal Epithelial Healing after Intravitreal Bevacizumab: A Clinical and Experimental Study

    PubMed Central

    Colombres, Gustavo A; Gramajo, Ana L; Arrambide, Maria P; Juarez, Silvina M; Arevalo, J Fernando; Bar, Jorge; Juarez, Claudio P; Luna, Jose D

    2011-01-01

    Purpose To report corneal epithelial defects (CEDs) and delayed epithelial healing after intravitreal bevacizumab (IVB) injection and to describe delayed corneal epithelial healing with topical administration of bevacizumab in an experimental rabbit model. Methods A retrospective chart review was performed on 850 eyes of 850 patients with neovascular eye disease and diabetic macular edema who had received 1.25 to 2.5 mg IVB. In the experimental arm of the study, photorefractive keratectomy was used to create a 3 mm CED in the right eyes of 18 New Zealand rabbits which were then randomized to three equal groups. All rabbits received topical antibiotics, additionally those in group A received topical bevacizumab and animals in group B were treated with topical corticosteroids. The rate of epithelial healing was assessed at different time points using slitlamp photography. Results In the clinical study, seven eyes of seven subjects developed CEDs the day after IVB injection. All of these eyes had preexisting corneal edema. The healing period ranged from 3 to 38 days (average 11 days) despite appropriate medical management. In the experimental study, topical bevacizumab and corticosteroids both significantly hindered corneal epithelial healing at 12 and 24 hours. Conclusion Bevacizumab was demonstrated to cause CEDs in clinical settings. Moreover, corneal epithelial healing was delayed by topical application of bevacizumab, in the experimental model. These short-term results suggest that corneal edema may be considered as a risk factor for epithelial defects after IVB. PMID:22454702

  1. Effects of Lutein on Hyperosmoticity-Induced Upregulation of IL-6 in Cultured Corneal Epithelial Cells and Its Relevant Signal Pathways

    PubMed Central

    Chao, Shih-Chun; Nien, Chan-Wei; Iacob, Codrin; Hu, Dan-Ning; Huang, Sheng-Chieh

    2016-01-01

    Dry eye is a common disorder characterized by deficiency of tear. Hyperosmoticity of tear stimulates inflammation and damage of ocular surface tissues and plays an essential role in the pathogenesis of dry eye. Cultured human corneal epithelial (CE) cells were used for the study of effects of lutein and hyperosmoticity on the secretion of IL-6 by CE cells. Cell viability of CE cells was not affected by lutein at 1–10 μM as determined by MTT assay. Hyperosmoticity significantly elevated the secretion of IL-6 by CE cells as measured by ELISA analysis. The constitutive secretion of IL-6 was not affected by lutein. Lutein significantly and dose-dependently inhibited hyperosmoticity-induced secretion of IL-6. Phosphorylated- (p)- p38 MAPK, p-JNK levels in cell lysates and NF-κB levels in cell nuclear extracts were increased by being exposed to hyperosmotic medium. JNK, p38, and NF-κB inhibitors decreased hyperosmoticity-induced secretion of IL-6. Lutein significantly inhibited hyperosmoticity-induced elevation of NF-κB, p38, and p-JNK levels. We demonstrated that lutein inhibited hyperosmoticity-induced secretion of IL-6 in CE cells through the deactivation of p38, JNK, and NF-κB pathways. Lutein may be a promising agent to be explored for the treatment of dry eye. PMID:27047687

  2. Corneal-shaping electrode

    DOEpatents

    Doss, James D.; Hutson, Richard L.

    1982-01-01

    The disclosure relates to a circulating saline electrode for changing corneal shape in eyes. The electrode comprises a tubular nonconductive electrode housing having an annular expanded base which has a surface substantially matched to a subject corneal surface. A tubular conductive electrode connected to a radiofrequency generating source is disposed within the electrode housing and longitudinally aligned therewith. The electrode has a generally hemispherical head having at least one orifice. Saline solution is circulated through the apparatus and over the cornea to cool the corneal surface while radiofrequency electric current emitted from the electrode flows therefrom through the cornea to a second electrode, on the rear of the head. This current heats the deep corneal stroma and thereby effects corneal reshaping as a biological response to the heat.

  3. Corneal cells for regeneration.

    PubMed

    Kinoshita, S; Nakamura, T

    2005-01-01

    In cases of corneal epithelial stem cell deficiency where ocular surface reconstruction is required, corneal epithelial replacement using a tissue engineering technique shows great potential. Autologous cultivated corneal epithelial stem cell sheets are the safest and most reliable forms of sheet we can use for such treatment; however, they are not useful for treating bilaterally affected ocular surface disorders. In order to treat such cases, we must choose either an allogeneic cultivated corneal epithelial sheet or an autologous cultivated oral mucosal epithelial sheet. If we use the former, the threat of immunological reaction must be dealt with. Therefore, it is imperative that we have a basic understanding of the immunological aspects of ocular surface reconstruction using allogeneic tissues. When using an autologous cultivated oral mucosal epithelial sheet, a basic understanding of ocular surface epithelial biology is required as the sheet is not exactly the same as corneal epithelium. PMID:16080287

  4. Brain edema in diseases of different etiology.

    PubMed

    Adeva, María M; Souto, Gema; Donapetry, Cristóbal; Portals, Manuel; Rodriguez, Alberto; Lamas, David

    2012-07-01

    Cerebral edema is a potentially life-threatening complication shared by diseases of different etiology, such as diabetic ketoacidosis, acute liver failure, high altitude exposure, dialysis disequilibrium syndrome, and salicylate intoxication. Pulmonary edema is also habitually present in these disorders, indicating that the microcirculatory disturbance causing edema is not confined to the brain. Both cerebral and pulmonary subclinical edema may be detected before it becomes clinically evident. Available evidence suggests that tissue hypoxia or intracellular acidosis is a commonality occurring in all of these disorders. Tissue ischemia induces physiological compensatory mechanisms to ensure cell oxygenation and carbon dioxide removal from tissues, including hyperventilation, elevation of red blood cell 2,3-bisphosphoglycerate content, and capillary vasodilatation. Clinical, laboratory, and necropsy findings in these diseases confirm the occurrence of low plasma carbon dioxide partial pressure, increased erythrocyte 2,3-bisphosphoglycerate concentration, and capillary vasodilatation with increased vascular permeability in all of them. Baseline tissue hypoxia or intracellular acidosis induced by the disease may further deteriorate when tissue oxygen requirement is no longer matched to oxygen delivery resulting in massive capillary vasodilatation with increased vascular permeability and plasma fluid leakage into the interstitial compartment leading to edema affecting the brain, lung, and other organs. Causative factors involved in the progression from physiological adaptation to devastating clinical edema are not well known and may include uncontrolled disease, malfunctioning adaptive responses, or unknown factors. The role of carbon monoxide and local nitric oxide production influencing tissue oxygenation is unclear. PMID:22579570

  5. Effects of electroacupuncture preconditioning on jugular vein glucose level and cerebral edema in rats undergoing cerebral ischemia reperfusion that induced injury

    PubMed Central

    Wan, Qiuxia; Pan, Peng; Xu, Changqing; Li, Wenzhi

    2014-01-01

    Objective: To determine the effects of electroacupuncture (EA) preconditioning on the blood glucose level in jugular vein and water content in brain tissues in rats undergoing cerebral ischemia reperfusion that induced injury. Methods: 90 healthy male Wister rats were randomly assigned to 3 groups: sham-operation (SH) group, cerebral ischemia reperfusion (IR) group and electroacupuncture (EA) preconditioning plus IR group. EA group was pretreated with EA delivered to acupoints of “Baihui” (Du 20) and “Shuigou” (Du 26) 30 min before cerebral ischemia. Results: No marked difference was observed in brain water content 2 h after procedure in IR group, SH group and EA group. Compared with SH group, the brain water contents in IR group and EA group were significantly higher 6 h after reperfusion and peaked at 48 h (P < 0.01). The blood glucose levels in EA and IR groups were significantly higher than that of SH group 2 h after reperfusion, which peaked at 6 h and tended to decline up to 24 h after reperfusion (P < 0.01). 2 h, 6 h, and 24 h after reperfusion, EA group had significantly lower blood glucose levels than IR group (P < 0.01). Conclusion: Electroacupuncture preconditioning can significantly inhibit the augmentation of the blood glucose level and attenuate cerebral edema induced by reperfusion, which leads to alleviation of injury caused by ischemia reperfusion. PMID:25550958

  6. Lipopolysaccharide-induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate stimulation of AC10.

    PubMed

    Nickols, Jordan; Obiako, Boniface; Ramila, K C; Putinta, Kevin; Schilling, Sarah; Sayner, Sarah L

    2015-12-15

    Bacteria-induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome. Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized: whether cAMP is barrier-protective or -disruptive depends on the compartment (plasma membrane or cytosol, respectively) in which the signal is generated. The mammalian soluble adenylyl cyclase isoform 10 (AC10) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. We tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability are dependent on extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent on extracellular bicarbonate: LPS-induced barrier failure and increased permeability are exacerbated in elevated bicarbonate compared with low extracellular bicarbonate. The AC10 inhibitor KH7 attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase Kf in the presence of minimal perfusate bicarbonate. An increase in perfusate bicarbonate to the physiological range (24 mM) revealed the LPS-induced increase in Kf, which was attenuated by KH7. Furthermore, in PMVECs treated with LPS for 6 h, there was a dose-dependent increase in AC10 expression. Thus these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10. PMID:26475732

  7. Anti-inflammatory effects of anthocyanins-rich extract from bilberry (Vaccinium myrtillus L.) on croton oil-induced ear edema and Propionibacterium acnes plus LPS-induced liver damage in mice.

    PubMed

    Luo, Hui; Lv, Xiao-Dan; Wang, Guo-En; Li, Yi-Fang; Kurihara, Hiroshi; He, Rong-Rong

    2014-08-01

    Bilberry (Vaccinium myrtillus L.) has been known to play a protective role in human health due to its high anthocyanin content. This study investigated the anti-inflammatory effects of bilberry extract (BE, containing 42.04% anthocyanin) on Propionibacterium acnes (P. acnes) plus lipopolysaccharide (LPS) induced liver injury and croton oil-induced ear edema in mice. Results showed that BE could effectively inhibit croton oil-induced ear edema and liver inflammation provoked by P. acnes plus LPS, as reflected by the reduced plasma alanine aminotransferase and aspartate aminotransferase activities. These findings were confirmed by hepatic pathological examination. Moreover, BE administration markedly suppressed the increase of liver mRNA levels of iNOS, TNF-α, IL-1β and IL-6, and the protein levels of iNOS, TNF-α and NF-κB. In addition, liver malondialdehyde and NO contents were significantly reduced by BE treatment. These results indicated that BE has potent protective effects on acute and immunological inflammation, which might contribute to the study of the anti-inflammatory effects of natural products and healthy food. PMID:24548119

  8. Proton nuclear magnetic resonance studies on brain edema

    SciTech Connect

    Naruse, S.; Horikawa, Y.; Tanaka, C.; Hirakawa, K.; Nishikawa, H.; Yoshizaki, K.

    1982-06-01

    The water in normal and edematous brain tissues of rats was studied by the pulse nuclear magnetic resonance (NMR) technique, measuring the longitudinal relaxation time (T1) and the transverse relaxation time (T2). In the normal brain, T1 and T2 were single components, both shorter than in pure water. Prolongation and separation of T2 into two components, one fast and one slow, were the characteristic findings in brain edema induced by both cold injury and triethyl tin (TET), although some differences between the two types of edema existed in the content of the lesion and in the degree of changes in T1 and T2 values. Quantitative analysis of T1 and T2 values in their time course relating to water content demonstrated that prolongation of T1 referred to the volume of increased water in tissues examined, and that two phases of T2 reflected the distribution and the content of the edema fluid. From the analysis of the slow component of T2 versus water content during edema formation, it was demonstrated that the increase in edema fluid was steady, and its content was constant during formation of TET-induced edema. On the contrary, during the formation of cold-injury edema, water-rich edema fluid increased during the initial few hours, and protein-rich edema fluid increased thereafter. It was concluded that proton NMR relaxation time measurements may provide new understanding in the field of brain edema research.

  9. Corneal blindness and xenotransplantation.

    PubMed

    Lamm, Vladimir; Hara, Hidetaka; Mammen, Alex; Dhaliwal, Deepinder; Cooper, David K C

    2014-01-01

    Approximately 39 million people are blind worldwide, with an estimated 285 million visually impaired. The developing world shoulders 90% of the world's blindness, with 80% of causative diseases being preventable or treatable. Blindness has a major detrimental impact on the patient, community, and healthcare spending. Corneal diseases are significant causes of blindness, affecting at least 4 million people worldwide. The prevalence of corneal disease varies between parts of the world. Trachoma, for instance, is the second leading cause of blindness in Africa, after cataracts, but is rarely found today in developed nations. When preventive strategies have failed, corneal transplantation is the most effective treatment for advanced corneal disease. The major surgical techniques for corneal transplantation include penetrating keratoplasty (PK), anterior lamellar keratoplasty, and endothelial keratoplasty (EK). Indications for corneal transplantation vary between countries, with Fuchs' dystrophy being the leading indication in the USA and keratoconus in Australia. With the exception of the USA, where EK will soon overtake PK as the most common surgical procedure, PK is the overwhelming procedure of choice. Success using corneal grafts in developing nations, such as Nepal, demonstrates the feasibility of corneal transplantation on a global scale. The number of suitable corneas from deceased human donors that becomes available will never be sufficient, and so research into various alternatives, for example stem cells, amniotic membrane transplantation, synthetic and biosynthetic corneas, and xenotransplantation, is progressing. While each of these has potential, we suggest that xenotransplantation holds the greatest potential for a corneal replacement. With the increasing availability of genetically engineered pigs, pig corneas may alleviate the global shortage of corneas in the near future. PMID:25268248

  10. Donor corneal tissue evaluation.

    PubMed

    Saini, J S; Reddy, M K; Sharma, S; Wagh, S

    1996-03-01

    Proper evaluation of donor cornea is critical to the success of corneal transplantation. Attention must be paid to the cause of death and ocular condition as several general and ocular diseases constitute contraindications for donor corneal usage. Death to enucleation time should be noted. Gross examination and slit lamp biomicroscopy are mandatory for the evaluation of the donor eye while specular microscopy adds another useful dimension to information regarding donor cornea. This article provides a comprehensive review of all the aspects of donor corneal evaluation as practised today worldwide. PMID:8828299

  11. Combining femtosecond laser ablation and diode laser welding in lamellar and endothelial corneal transplants

    NASA Astrophysics Data System (ADS)

    Pini, Roberto; Rossi, Francesca; Matteini, Paolo; Ratto, Fulvio; Menabuoni, Luca; Lenzetti, Ivo; Yoo, Sonia H.; Parel, Jean-Marie

    2008-02-01

    Based on our previous clinical experiences in minimally invasive diode laser-induced welding of corneal tissue in penetrating keratoplasty (PK), i.e. full-thickness transplant of the cornea, we combined this technique with the use of a femtosecond laser for applications in lamellar (LK) and endothelial (EK) keratoplasty. In LK, the femtosecond laser was used to prepare donor button and recipient corneal bed; the wound edges were stained with a water solution of Indocyanine Green (ICG) and then irradiated with a diode laser emitting in CW mode to induce stromal welding. Intraoperatory observations and follow-up results up to 6 months indicated the formation of a smooth stromal interface, total absence of edema as well as inflammation, and reduction of post-operative astigmatism, as compared with conventional suturing procedures. In EK the femtosecond laser was used for the preparation of a 100 μm thick, 8.5mm diameter donor corneal endothelium flap. The flap stromal side was stained with ICG. After stripping the recipient Descemet's membrane and endothelium, the donor flap was positioned in the anterior chamber on the inner face of the cornea by an air bubble and secured to the recipient cornea by diode laser pulses delivered by means of a fiberoptic contact probe introduced in the anterior chamber, which produced welding spots of 200 μm diameter. Femtosecond laser sculpturing of the donor cornea provided lamellar and endothelial flaps of preset and constant thickness. Diode laserinduced welding showed a unique potential to permanently secure the donor flap in place, avoiding postoperative displacement and inflammation reaction.

  12. Aronia melanocarpa Concentrate Ameliorates Pro-Inflammatory Responses in HaCaT Keratinocytes and 12-O-Tetradecanoylphorbol-13-Acetate-Induced Ear Edema in Mice.

    PubMed

    Goh, Ah Ra; Youn, Gi Soo; Yoo, Ki-Yeon; Won, Moo Ho; Han, Sang-Zin; Lim, Soon Sung; Lee, Keun Wook; Choi, Soo Young; Park, Jinseu

    2016-07-01

    Abnormal expression of pro-inflammatory mediators such as cell adhesion molecules and cytokines has been implicated in various inflammatory skin diseases, including atopic dermatitis. In this study, we investigated the anti-inflammatory activity of Aronia melanocarpa concentrate (AC) and its action mechanisms using in vivo and in vitro skin inflammation models. Topical application of AC on mouse ears significantly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema formation, as judged by measuring ear thickness and weight, and histological analysis. Topical administration of AC also reduced the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in TPA-stimulated mouse ears. Pretreatment with AC suppressed TNF-α-induced ICAM-I expression and subsequent monocyte adhesiveness in human keratinocyte cell line HaCaT. In addition, AC significantly decreased intracellular reactive oxygen species (ROS) generation as well as mitogen-activated protein kinase (MAPK) activation in TNF-α-stimulated HaCaT cells. AC and its constituent cyanidin 3-glucoside also attenuated TNF-α-induced IKK activation, IκB degradation, p65 phosphorylation/nuclear translocation, and p65 DNA binding activity in HaCaT cells. Overall, our results indicate that AC exerts anti-inflammatory activities by inhibiting expression of pro-inflammatory mediators in vitro and in vivo possibly through suppression of ROS-MAPK-NF-κB signaling pathways. Therefore, AC may be developed as a therapeutic agent to treat various inflammatory skin diseases. PMID:27331630

  13. Gamma-Irradiated Sterile Cornea for Use in Corneal Transplants in a Rabbit Model

    PubMed Central

    Yoshida, Junko; Heflin, Thomas; Zambrano, Andrea; Pan, Qing; Meng, Huan; Wang, Jiangxia; Stark, Walter J.; Daoud, Yassine J.

    2015-01-01

    Purpose: Gamma irradiated corneas in which the donor keratocytes and endothelial cells are eliminated are effective as corneal lamellar and glaucoma patch grafts. In addition, gamma irradiation causes collagen cross inking, which stiffens collagen fibrils. This study evaluated gamma irradiated corneas for use in corneal transplantations in a rabbit model comparing graft clarity, corneal neovascularization, and edema. Methods: Penetrating keratoplasty was performed on rabbits using four types of corneal grafts: Fresh cornea with endothelium, gamma irradiated cornea, cryopreserved cornea, and fresh cornea without endothelium. Slit lamp examination was performed at postoperative week (POW) one, two, and four. Corneal clarity, edema, and vascularization were graded. Confocal microscopy and histopathological evaluation were performed. A P < 0.05 was statistically significant. Results: For all postoperative examinations, the corneal clarity and edema were statistically significantly better in eyes that received fresh cornea with endothelium compared to the other three groups (P < 0.05). At POW 1, gamma irradiated cornea scored better than the cryopreserved and fresh cornea without endothelium groups in clarity (0.9 vs. 1.5 and 2.6, respectively), and edema (0.6 vs. 0.8 and 2.0, respectively). The gamma irradiated corneas, cryopreserved corneas and the fresh corneas without endothelium, developed haze and edema after POW 2. Gamma irradiated cornea remained statistically significantly clearer than cryopreserved and fresh cornea without endothelium during the observation period (P < 0.05). Histopathology indicated an absence of keratocytes in gamma irradiated cornea. Conclusion: Gamma irradiated corneas remained clearer and thinner than the cryopreserved cornea and fresh cornea without endothelium. However, this outcome is transient. Gamma irradiated corneas are useful for lamellar and patch grafts, but cannot be used for penetrating keratoplasty. PMID:26180475

  14. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury

    PubMed Central

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F.; Liu, Boyi; Kaelberer, Melanie M.; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S.; Ye, Guosen; Willette, Robert N.; Thorneloe, Kevin S.; Bradshaw, Heather B.; Matalon, Sadis

    2014-01-01

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  15. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury.

    PubMed

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F; Liu, Boyi; Kaelberer, Melanie M; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S; Ye, Guosen; Willette, Robert N; Thorneloe, Kevin S; Bradshaw, Heather B; Matalon, Sadis; Jordt, Sven-Eric

    2014-07-15

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  16. Bioassay-guided chemical study of the anti-inflammatory effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-induced ear edema.

    PubMed

    Susunaga-Notario, Ana del Carmen; Pérez-Gutiérrez, Salud; Zavala-Sánchez, Miguel Angel; Almanza-Pérez, Julio Cesar; Gutiérrez-Carrillo, Atilano; Arrieta-Báez, Daniel; López-López, Ana Laura; Román-Ramos, Rubén; Flores-Sáenz, José Luis Eduardo; Alarcón-Aguilar, Francisco Javier

    2014-01-01

    Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractions were obtained from the bioassay-guided chemical study, including a white precipitate from fractions 2 and 3. Although none of the nine fractions presented anti-inflammatory activity, the white precipitate exhibited pharmacological activity. It was chemically characterized using mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, resulting in a mixture of three aliphatic esters, which were identified as the principal constituents: hexyl tetradecanoate (C20H40O2), heptyl tetradecanoate (C21H42O2) and octyl tetradecanoate (C22H44O2). This research provides, for the first time, evidence of the anti-inflammatory and anti-proliferative properties of compounds isolated from Senna villosa. PMID:25029073

  17. Downregulation of miR-18a induces CTGF and promotes proliferation and migration of sodium hyaluronate treated human corneal epithelial cells.

    PubMed

    Guo, Yingzhuo; Lu, Xiaohe; Wang, Hua

    2016-10-10

    Properly controlled corneal epithelial wound healing is critical for health of cornea, which involves cell proliferation, migration, anchoring and differentiation. Sodium hyaluronate (SH) has been proven to exert beneficial pharmacological effect on corneal wound healing, though the underlying mechanism remained open to investigation. MicroRNAs (miRNAs) are small single-stranded RNAs that could bind to 3'UTR of mRNAs of target genes. The multi-target regulation of miRNAs may favor treatment of corneal wound given the complicated processes implicated in the healing process, which has inspired initiatives to develop miRNA therapy in corneal wound healing. In this light, we used miRNAs profiling to detect whether miRNAs are also implicated in the mechanism underlying the stimulatory effect of SH on corneal epithelial wound healing. We found miR-18a was most susceptible to SH treatment, the target prediction of which were enriched in a bunch of pathways implicated in corneal wound healing. Connective tissue growth factor (CTGF) was found to be overrepresented in most significant enriched pathways and was experimentally confirmed as a bona fide target of miR-18a, which modulated cell migration and proliferation of human corneal epithelial cells. PMID:27390086

  18. Corneal cross-linking.

    PubMed

    Randleman, J Bradley; Khandelwal, Sumitra S; Hafezi, Farhad

    2015-01-01

    Since its inception in the late 1990s, corneal cross-linking has grown from an interesting concept to a primary treatment for corneal ectatic disease worldwide. Using a combination of ultraviolet-A light and a chromophore (vitamin B2, riboflavin), the cornea can be stiffened, usually with a single application, and progressive thinning diseases such as keratoconus arrested. Despite being in clinical use for many years, some of the underlying processes, such as the role of oxygen and the optimal treatment times, are still being worked out. More than a treatment technique, corneal cross-links represent a physiological principle of connective tissue, which may explain the enormous versatility of the method. We highlight the history of corneal cross-linking, the scientific underpinnings of current techniques, evolving clinical treatment parameters, and the use of cross-linking in combination with refractive surgery and for the treatment of infectious keratitis. PMID:25980780

  19. Importance of Corneal Thickness

    MedlinePlus

    ... News About Us Donate In This Section The Importance of Corneal Thickness email Send this article to ... is important because it can mask an accurate reading of eye pressure, causing doctors to treat you ...

  20. Refractive corneal surgery - discharge

    MedlinePlus

    Nearsightedness surgery - discharge; Refractive surgery - discharge; LASIK - discharge; PRK - discharge ... You had refractive corneal surgery to help improve your vision. This surgery uses a laser to reshape your cornea. It corrects ...

  1. Effects of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell counts

    PubMed Central

    Gao, Feng; Lin, Tao; Pan, Yingzhe

    2016-01-01

    Diabetic keratopathy is an ocular complication that occurs with diabetes. In the present study, the effect of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell count was investigated. One hundred and eighty diabetic patients (360 eyes) were enrolled in the study during the period from March, 2012 to March, 2013. The patients were divided into three age groups: <5, 5–10 and >10 years, with 60 patients per group (120 eyes). During the same period, 60 healthy cases (120 eyes) were selected and labeled as the normal control group. The Pentacam was used to measure the corneal optical density, and central corneal thickness. Specular microscopy was used to examine the corneal endothelial cell density. The coefficient of partial correlation was used to control age and correlate the analysis between the corneal optical density, corneal endothelial cell density, and central corneal thickness. The stage of the disease, the medial and intimal corneal optical density and central corneal thickness was analyzed in the diabetes group. The corneal optical density in the diabetes group increased compared with that of the normal control group. The medial and intimal corneal optical density and central corneal thickness were positively correlated with the course of the disease. However, the corneal endothelial cell density was not associated with the course of diabetes. There was a positive association between the medial and intimal corneal optical density and central corneal thickness of the diabetic patients. In conclusion, the results of the present study show that medial and intimal corneal optical density and central corneal thickness were sensitive indicators for early diabetic keratopathy.

  2. Models of Inflammation: Carrageenan- or Complete Freund’s Adjuvant-Induced Edema and Hypersensitivity in the Rat

    PubMed Central

    Fehrenbacher, Jill C.; Vasko, Michael R.; Duarte, Djane B.

    2012-01-01

    Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds to reverse cutaneous hypersensitivity. This protocol details methods to elicit and measure carrageenan- and complete Freund’s adjuvant-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections of either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) and by the trigeminal ganglion neurons (vibrissal pad). PMID:22382999

  3. Models of Inflammation: Carrageenan- or Complete Freund's Adjuvant (CFA)-Induced Edema and Hypersensitivity in the Rat.

    PubMed

    McCarson, Kenneth E

    2015-01-01

    Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this unit are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). PMID:26331888

  4. Quantitative proteomic analysis of mice corneal tissues reveals angiogenesis-related proteins involved in corneal neovascularization.

    PubMed

    Shen, Minqian; Tao, Yimin; Feng, Yifan; Liu, Xing; Yuan, Fei; Zhou, Hu

    2016-07-01

    Corneal neovascularization (CNV) was induced in Balb/c mice by alkali burns in the central area of the cornea with a diameter of 2.5mm. After fourteen days, the cornea from one eye was collected for histological staining for CNV examination, while the cornea from the other eye of the same mouse was harvested for proteomic analysis. The label-free quantitative proteomic approach was applied to analyze five normal corneal tissues (normal group mice n=5) and five corresponding neovascularized corneal tissues (model group mice n=5). A total of 2124 proteins were identified, and 1682 proteins were quantified from these corneal tissues. Among these quantified proteins, 290 proteins were significantly changed between normal and alkali burned corneal tissues. Of these significantly changed proteins, 35 were reported or predicted as angiogenesis-related proteins. Then, these 35 proteins were analyzed using Ingenuity Pathway Analysis Software, resulting in 26 proteins enriched and connected to each other in the protein-protein interaction network, such as Lcn-2, αB-crystallin and Serpinf1 (PEDF). These three significantly changed proteins were selected for further Western blotting validation. Consistent with the quantitative proteomic results, Western blotting showed that Lcn-2 and αB-crystallin were significantly up-regulated in CNV model, while PEDF was down-regulated. This study provided increased understanding of angiogenesis-related proteins involved in corneal vascular development, which will be useful in the ophthalmic clinic of specifically target angiogenesis. PMID:27049463

  5. Hypertonicity-induced p38MAPK activation elicits recovery of corneal epithelial cell volume and layer integrity.

    PubMed

    Bildin, V N; Wang, Z; Iserovich, P; Reinach, P S

    2003-05-01

    In hypertonicity-stressed (i.e., 600 mOsm) SV40-immortalized rabbit and human corneal epithelial cell layers (RCEC and HCEC, respectively), we characterized the relationship between time-dependent changes in translayer resistance, relative cell volume and modulation of MAPK superfamily activities. Sulforhodamine B permeability initially increased by 1.4- and 2-fold in RCEC and HCEC, respectively. Subsequently, recovery to its isotonic level only occurred in RCEC. Light scattering revealed that in RCEC 1) regulatory volume increase (RVI) extent was 20% greater; 2) RVI half-time was 2.5-fold shorter. However, inhibition of Na-K-2Cl cotransporter and Na/K-ATPase activity suppressed the RVI response more in HCEC. MAPK activity changes were as follows: 1) p38 was wave-like and faster as well as larger in RCEC than in HCEC (90- and 18-fold, respectively); 2) increases in SAPK/JNK activity were negligible in comparison to those of p38; 3) Erk1/2 activity declined to 30-40% of their basal values. SB203580, a specific p38 inhibitor, dose dependently suppressed the RVI responses in both cell lines. However, neither U0126, which inhibits MEK, the kinase upstream of Erk, nor SP600125, inhibitor of SAPK/JNK, had any effect on this response. Taken together, sufficient activation of the p38 limb of the MAPK superfamily during a hypertonic challenge is essential for maintaining epithelial cell volume and translayer resistance. On the other hand, Erk1/2 activity restoration seems to be dependent on cell volume recovery. PMID:12879161

  6. Reactive oxygen species activated NLRP3 inflammasomes initiate inflammation in hyperosmolarity stressed human corneal epithelial cells and environment-induced dry eye patients.

    PubMed

    Zheng, Qinxiang; Ren, Yueping; Reinach, Peter S; Xiao, Bing; Lu, Huihui; Zhu, Yirui; Qu, Jia; Chen, Wei

    2015-05-01

    In studies on dry eye (DE) disease, an association has been identified between tear film hyperosmolarity and inflammation severity elicited through receptor-induced increases in proinflammatory cytokine and chemokine release. These immune reactions might be mediated by inflammasomes, macromolecular complexes mounted around the NLRP3 protein and can be activated by reactive oxygen species (ROS) over-generation. Hence in this study we determine whether: a) ROS activated NLRP3 inflammasomes mediate hyperosmotic stress-induced inflammation in human corneal epithelial cells (HCECs); b) the ROS-NLRP3-IL-1β axis activation is associated with environment-induced DE. Immortalized HCECs were exposed to 500 mOsm medium in the presence and absence of a ROS inhibitor, N-acetyl-l-cysteine (NAC). HCECs transfected with NLRP3 siRNA or a negative control (NC) siRNA. Intracellular ROS was measured by fluorometric analysis using the probe 2',7'-dichlorofluorescin diacetate (DCFH-DA). Real-time PCR evaluated NLRP3, ASC, pro-caspase-1 and pro-IL-1β mRNA levels. Western blot analysis assessed NLRP3 protein expression whereas caspase-1 activity was determined with a fluorometric assay. Bioactive IL-1β release was assessed by ELISA. ROS production, NLRP3 inflammasome and pro-IL-1β gene expression as well as IL-1β secretion were also evaluated in the conjunctival epithelial cells and tear fluid samples of environment-induced DE patients and normal subjects. NAC suppressed hyperosmolarity-induced rises in ROS levels, NLRP3 inflammasome formation and activation, caspase-1 activity and IL-1β release. On the other hand, NLRP3 siRNA knockdown inhibited hyperosmotic stress-induced NLRP3 activation, which led to ASC, pro-caspase-1 and pro-IL-1β mRNA down-regulation followed by suppression of associated caspase-1 activity and IL-1β secretion. In addition, in ocular surface samples of environment-induced DE patients, ROS generation, NLRP3, ASC, pro-caspase-1 and pro-IL-1β gene expression

  7. Latest advances in edema

    NASA Technical Reports Server (NTRS)

    Villavicencio, J. L.; Hargens, A. R.; Pikoulicz, E.

    1996-01-01

    Basic concepts in the physiopathology of edema are reviewed. The mechanisms of fluid exchange across the capillary endothelium are explained. Interstitial flow and lymph formation are examined. Clinical disorders of tissue and lymphatic transport, microcirculatory derangements in venous disorders, protein disorders, and lymphatic system disorders are explored. Techniques for investigational imaging of the lymphatic system are explained.

  8. Anti-Inflammatory and Analgesic Effects of Pyeongwisan on LPS-Stimulated Murine Macrophages and Mouse Models of Acetic Acid-Induced Writhing Response and Xylene-Induced Ear Edema

    PubMed Central

    Oh, You-Chang; Jeong, Yun Hee; Cho, Won-Kyung; Ha, Jeong-Ho; Gu, Min Jung; Ma, Jin Yeul

    2015-01-01

    Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine to treat anorexia, abdominal distension, borborygmus and diarrhea caused by gastric catarrh, atony and dilatation. However, its effects on inflammation-related diseases are unknown. In this study, we investigated the biological effects of PW on lipopolysaccharide (LPS)-mediated inflammation in macrophages and on local inflammation in vivo. We investigated the biological effects of PW on the production of inflammatory mediators, pro-inflammatory cytokines and related products as well as the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated macrophages. Additionally, we evaluated the analgesic effect on the acetic acid-induced writhing response and the inhibitory activity on xylene-induced ear edema in mice. PW showed anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and interleukin-1β (IL-1β). In addition, PW strongly suppressed inducible nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO-1) expression and inhibited NF-κB activation and MAPK phosphorylation. Also, PW suppressed TNF-α, IL-6 and IL-1β cytokine production in LPS-stimulated peritoneal macrophage cells. Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema. We demonstrated the anti-inflammatory effects and inhibitory mechanism in macrophages as well as inhibitory activity of PW in vivo for the first time. Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance. PMID:25569097

  9. Characteristics of the low density corneal endothelial monolayer.

    PubMed

    Singh, Jorawer S; Haroldson, Thomas A; Patel, Sangita P

    2013-10-01

    Corneal endothelial cells form a leaky barrier on the posterior surface of the cornea, allowing influx of nutrient-carrying aqueous humor through the paracellular space and efflux of excess fluid. Corneal edema arises when the density of these non-proliferative endothelial cells declines from endothelial disease or intraocular surgery. The cellular changes occurring at low densities are ill-defined. We therefore investigated the paracellular pathway of corneal endothelial cell monolayers of varying density to determine alterations occurring in paracellular permeability and monolayer morphology. Primary cultures of bovine corneal endothelial cells (BCECs) were passaged onto permeable supports under varying culture conditions to obtain confluent monolayers of <1000, 1000-1999 and >2000 cells/mm(2). Culture growth was monitored by transendothelial electrical resistance measurements. Diffusional permeability to sodium fluorescein, FITC-dextran MW 4000 or FITC-dextran MW 20,000 was measured. Confluent cultures were also analyzed by immunofluorescence localization of the tight junction protein ZO-1 and by transmission electron microscopy. For comparison, we evaluated ZO-1 for low and high density human corneal endothelium. Our results showed that all BCEC cultures grew to the same final transendothelial electrical resistance regardless of final density. In the diffusional permeability assay, permeability increased significantly only for the smallest tracer molecule (sodium fluorescein) in the lowest density monolayers (<1000 cells/mm(2)). ZO-1 immunofluorescence distinctly localized to intercellular junctions in high density BCEC cultures but had more diffuse localization at lower densities. Transmission electron microscopy imaging revealed cells with thinner cross-sectional profiles and longer overlapping intercellular processes at low density relative to high density cultures. Low density human corneal endothelium lacked the diffuse ZO-1 distribution seen in BCECs

  10. Plasma infusions into porcine cerebral white matter induce early edema, oxidative stress, pro-inflammatory cytokine gene expression and DNA fragmentation: implications for white matter injury with increased blood-brain-barrier permeability.

    PubMed

    Wagner, Kenneth R; Dean, Christopher; Beiler, Shauna; Bryan, David W; Packard, Benjamin A; Smulian, A George; Linke, Michael J; de Courten-Myers, Gabrielle M

    2005-04-01

    Plasma infused into porcine cerebral white matter induces both acute interstitial and delayed vasogenic edema. Edematous white matter contains extracellular plasma proteins and rapidly induces oxidative stress as evidenced by increased protein carbonyl formation and heme oxygenase-1 induction. We tested the hypothesis that edematous white matter would also upregulate pro-inflammatory cytokine gene expression and develop DNA damage. We infused autologous plasma into the frontal hemispheric white matter of pentobarbital-anesthetized pigs. We monitored and controlled physiological variables and froze brains in situ at 1, 4 or 24 hrs. We determined edema volumes by computer-assisted morphometry. We measured white matter protein carbonyl formation by immunoblotting, cytokine gene expression by standard RT-PCR methods and DNA fragmentation by agarose gel electrophoresis. White matter edema developed acutely (1 hr) after plasma infusion and increased significantly in volume between 4 and 24 hrs. Protein carbonyl formation also occurred rapidly in edematous white matter with significant elevations (3 to 4-fold) already present at 1 hr. This increase remained through 24 hrs. Pro-inflammatory cytokine gene expression was also rapidly increased at 1 hr post-infusion. Evidence for DNA fragmentation began at 2 to 4 hrs, and a pattern indicative of both ongoing necrosis and apoptosis was robust by 24 hrs. Plasma protein accumulation in white matter induces acute edema development and a cascade of patho-chemical events including oxidative stress, pro-inflammatory cytokine gene expression and DNA damage. These results suggest that in diseases with increased blood-brain barrier (BBB) permeability or following intracerebral hemorrhage or traumatic brain injury, interstitial plasma can rapidly damage white matter. PMID:16181107

  11. An uncommon cause of acute pulmonary edema.

    PubMed

    Nepal, Santosh; Giri, Smith; Bhusal, Mohan; Siwakoti, Krishmita; Pathak, Ranjan

    2016-09-01

    Acute cardiogenic pulmonary edema secondary to catecholamine-induced cardiomyopathy is a very uncommon and fatal initial presentation of pheochromocytoma. However, with early clinical suspicion and aggressive management, the condition is reversible. This case report describes a patient who presented with hypertension, dyspnea, and cough with bloody streaks, and who recovered within 48 hours after appropriate treatment. PMID:27575897

  12. Autophagy in granular corneal dystrophy type 2.

    PubMed

    Choi, Seung-Il; Kim, Eung Kweon

    2016-03-01

    Autophagy is a lysosomal degradative process that is essential for cellular homeostasis and metabolic stress adaptation. Defective autophagy is involved in the pathogenesis of many diseases including granular corneal dystrophy type 2 (GCD2). GCD2 is an autosomal dominant disorder caused by substitution of histidine for arginine at codon 124 (R124H) in the transforming growth factor β-induced gene (TGFBI) on chromosome 5q31. Transforming growth factor β-induced protein (TGFBIp) is degraded by autophagy, but mutant-TGFBIp accumulates in autophagosomes and/or lysosomes, despite significant activation of basal autophagy, in GCD2 corneal fibroblasts. Furthermore, inhibition of autophagy induces cell death of GCD2 corneal fibroblasts through active caspase-3. As there is currently no pharmacological treatment for GCD2, development of novel therapies is required. A potential strategy for preventing cytoplasmic accumulation of mutant-TGFBIp in GCD2 corneal fibroblasts is to enhance mutant-TGFBIp degradation. This could be achieved by activation of the autophagic pathway. Here, we will consider the role and the potential therapeutic benefits of autophagy in GCD2, with focus on TGFBIp degradation, in light of the recently established role of autophagy in protein degradation. PMID:26386150

  13. Clinical aspects of corneal trachoma.

    PubMed Central

    Hosni, F A

    1978-01-01

    Classification of trachoma by site rather than density of opacities is better related to visual prognosis and helps in selection for graft surgery. The cases are divided into 3 groups: peripheral corneal opacities, central corneal opacities, and diffuse corneal opacities (ground-glass cornea). A central lesion has the poorest prognosis, especially in children. PMID:638107

  14. Understanding of the Viscoelastic Response of the Human Corneal Stroma Induced by Riboflavin/UV-A Cross-Linking at the Nano Level

    PubMed Central

    Labate, Cristina; De Santo, Maria Penelope; Lombardo, Giuseppe; Lombardo, Marco

    2015-01-01

    Purpose To investigate the viscoelastic changes of the human cornea induced by riboflavin/UV-A cross-linking using Atomic Force Microscopy (AFM) at the nano level. Methods Seven eye bank donor corneas were investigated, after gently removing the epithelium, using a commercial AFM in the force spectroscopy mode. Silicon cantilevers with tip radius of 10 nm and spring elastic constants between 26- and 86-N/m were used to probe the viscoelastic properties of the anterior stroma up to 3 µm indentation depth. Five specimens were tested before and after riboflavin/UV-A cross-linking; the other two specimens were chemically cross-linked using glutaraldehyde 2.5% solution and used as controls. The Young’s modulus (E) and the hysteresis (H) of the corneal stroma were quantified as a function of the application load and scan rate. Results The Young’s modulus increased by a mean of 1.1-1.5 times after riboflavin/UV-A cross-linking (P<0.05). A higher increase of E, by a mean of 1.5-2.6 times, was found in chemically cross-linked specimens using glutaraldehyde 2.5% (P<0.05). The hysteresis decreased, by a mean of 0.9-1.5 times, in all specimens after riboflavin/UV-A cross-linking (P<0.05). A substantial decrease of H, ranging between 2.6 and 3.5 times with respect to baseline values, was observed in glutaraldehyde-treated corneas (P<0.05). Conclusions The present study provides the first evidence that riboflavin/UV-A cross-linking induces changes of the viscoelastic properties of the cornea at the scale of stromal molecular interactions. PMID:25830534

  15. In vivo corneal neovascularization imaging by optical-resolution photoacoustic microscopy

    PubMed Central

    Liu, Wenzhong; Schultz, Kathryn M.; Zhang, Kevin; Sasman, Amy; Gao, Fengli; Kume, Tsutomu; Zhang, Hao F.

    2014-01-01

    Corneal neovascularization leads to blurred vision, thus in vivo visualization is essential for pathological studies in animal models. Photoacoustic (PA) imaging can delineate microvasculature and hemodynamics noninvasively, which is suitable for investigating corneal neovascularization. In this study, we demonstrate in vivo imaging of corneal neovascularization in the mouse eye by optical-resolution photoacoustic microscopy (OR-PAM), where corneal neovascularization is induced by deliberate alkali burn injuries in C57BL6/J inbred mice corneas on the left eye. We used OR-PAM to image five mice with corneal alkali burn injuries; the uninjured eyes (right eye) in these mice are then used as the controls. Corneal images acquired by OR-PAM with and without alkali burn injury are compared, clear signs of corneal neovascularization are present in the OR-PAM images of injured eyes; the OR-PAM results are also confirmed by postmortem fluorescence-labeled confocal microscopy. PMID:25013754

  16. Corneal reepithelialization and anti-inflammatory agents.

    PubMed Central

    Srinivasan, B D

    1982-01-01

    These studies have demonstrated that nonsteroidal anti-inflammatory agents (cyclooxygenase and lipoxygenase inhibitors) can inhibit PMN arrival in the tear fluid following corneal injury but do not inhibit the reepithelialization either by corneal epithelial cells or by conjunctival epithelial cells. Therefore, they can be used safely in ocular inflammatory conditions even when corneal epithelial defects are present. Corticosteroids, on the other hand, inhibit reepithelialization by conjunctival epithelial cells and not by corneal epithelial cells in the doses tested. This inhibition does not occur with pretreatment prior to injury, suggesting that corticosteroids can be used clinically in conditions that have intact corneal epithelium without fear of slowing down wound healing should epithelial defects occur when not on steroid therapy. Furthermore, the steroid inhibition is temporary since there is a breakthrough in steroid inhibition with time, and occurs only if the steroids have been used shortly after deepithelialization. The steroid inhibition can be reversed by specific steroid antagonist, indicating that the steroid effect is mediated through specific receptors. An exciting and new hypothesis proposes that corticosteroids induce the formation of an inhibitory protein that inhibits the phospholipase enzyme to cause a block in arachidonic acid release from cell membranes. This mechanism of action may also be prevalent in the steroid effect on corneal reepithelialization, and experiments are under way to isolate this inhibitory protein from steroid-treated conjunctival epithelium. This isolation and pharmacologic characterization of this inhibitory protein is of obvious advantage to the field of ophthalmic therapeutics since this protein may have the anti-inflammatory potential of the steroids without their steroid sideeffects. Images FIGURE 3 a FIGURE 3 b PMID:6763806

  17. [Pay attention to the corneal epithelial cell dysfunction after cataract surgery].

    PubMed

    Sun, Xuguang; Wang, Sen

    2015-03-01

    Corneal epithelial dysfunction ( CED ) is the abnormality of the regeneration, conjunction, adhesion and immigration of the corneal epithelium cells without the decompensation of the corneal limbal cells. Due to the affection resulting from the systemic problems of patients and the management in the preoperative period, some of the patients at one to two weeks after cataract surgery will present the edema and fluorescein staining of the corneal epithelium. Without correct therapy, the defect of the epithelium, or even persisting ulceration of the cornea will occur. The key points of the management for CED are the early diagnosis and reasonable therapy. We suggest paying special attention to CED in the patients with metabolism diseases, abnormality of the tear film and long-term blepharitis. PMID:26268637

  18. Corneal decompensation following filtering surgery with the Ex-PRESS® mini glaucoma shunt device

    PubMed Central

    Tojo, Naoki; Hayashi, Atsushi; Miyakoshi, Akio

    2015-01-01

    Purpose To report a case of corneal decompensation due to the Ex-PRESS® mini glaucoma shunt device (Ex-PRESS). Patient and methods A 75-year-old man had pseudoexfoliation glaucoma in his right eye. He underwent filtration surgery with Ex-PRESS. His intraocular pressure was 7 mmHg after 9 months. Results We observed partial decompensation of the corneal endothelium adjacent to the filtering bleb. Specular microscopy revealed a marked decrease in the endothelial cell density at the center of the cornea. Conclusion Anterior segment optical coherence tomography is very useful for evaluating corneal edema and the position of Ex-PRESS. It is important to follow up with an examination of the corneal endothelial cells. PMID:25834385

  19. Advances in corneal preservation.

    PubMed Central

    Lindstrom, R L

    1990-01-01

    The functional status of the endothelium and sustained corneal deturgescence after corneal preservation are of great clinical importance and have been primary goals in the development of corneal storage media. In our investigational studies we have specifically addressed the improvement of the quality of donor tissue after 4 degrees C storage, the extension of corneal preservation time, the enhancement of corneal wound healing, and the reduction of the normal progressive loss of endothelial cells postkeratoplasty. Specifically we have developed in vitro HCE cell and epithelial cell culture models that can accurately reflect the response of human corneal tissue in vivo. These models have been utilized to study the effects of growth factors and medium components in relation to their biocompatibility and efficacy in the development of improved corneal preservation solutions. Our laboratory investigated in vitro conditions that allowed human corneal endothelium to shift from a nonproliferative state, in which they remain viable and metabolically active, to a proliferative, mitotically active state. Isolation techniques developed in our laboratory have enabled the establishment of primary and subsequent subcultures of human corneal endothelium that retain the attributes of native endothelium. These in vitro conditions maintain HCE cells in a proliferative state, actively undergoing mitosis. A quantitative bioassay has been developed to determine the effects of various test medium in the stimulation or inhibition of DNA synthesis. In attempting to learn more about the events that occur during in vitro endothelial cell isolation, cell reattachment, extracellular matrix interaction and migrating during subculture, SEM was done on isolated HCE cells incubated in CSM. These studies suggest that the components of the extracellular matrix modulate the growth response of HCE cells, and play a role in regulating proliferation and migration. These observations are important in

  20. Immune Privilege of Corneal Allografts

    PubMed Central

    Niederkorn, Jerry Y.; Larkin, D. Frank P.

    2013-01-01

    Corneal transplantation has been performed successfully for over 100 years. Normally, HLA typing and systemic immunosuppressive drugs are not utilized, yet 90% of corneal allografts survive. In rodents, corneal allografts representing maximal histoincompatibility enjoy >50% survival even without immunosuppressive drugs. By contrast, other categories of transplants are invariably rejected in such donor/host combinations. The acceptance of corneal allografts compared to other categories of allografts is called immune privilege. The cornea expresses factors that contribute to immune privilege by preventing the induction and expression of immune responses to histocompatibility antigens on the corneal allograft. Among these are soluble and cell membrane molecules that block immune effector elements and also apoptosis of T lymphocytes. However, some conditions rob the corneal allograft of its immune privilege and promote rejection, which remains the leading cause of corneal allograft failure. Recent studies have examined new strategies for restoring immune privilege to such high-risk hosts. PMID:20482389

  1. Two Different Regulatory T Cell Populations That Promote Corneal Allograft Survival

    PubMed Central

    Cunnusamy, Khrishen; Paunicka, Kathryn; Reyes, Nancy; Yang, Wanhua; Chen, Peter W.

    2010-01-01

    Purpose. To compare and contrast the T regulatory cells (Tregs) induced by anterior chamber (AC) injection of antigen with those induced by orthotopic corneal allografts. Methods. Anterior chamber–associated immune deviation (ACAID) Tregs were induced by injecting C57BL/6 spleen cells into the AC of BALB/c mice. Delayed-type hypersensitivity responses to C57BL/6 alloantigens were evaluated by a conventional ear swelling assay. Corneal allograft Tregs were induced by applying orthotopic C57BL/6 corneal allografts onto BALB/c hosts. The effects of anti-CD25, anti-CD8, anti-interferon-γ (IFN-γ), anti-IL-17A, or cyclophosphamide treatments on corneal allograft survival and ACAID were evaluated. Results. Administration of either anti-CD25 or anti-IFN-γ antibodies prevented the expression of ACAID and abolished the immune privilege of corneal allografts. By contrast, in vivo treatment with anti-CD8 antibody abrogated ACAID but had no effect on corneal allograft survival. Further discordance between ACAID and corneal allograft survival emerged in experiments in which the induction of allergic conjunctivitis or the administration of anti-IL-17A abolished the immune privilege of corneal allografts but had no effect on the induction or expression of ACAID. Conclusions. Although orthotopic corneal allografts are strategically located for the induction of ACAID by the sloughing of corneal cells into the AC, the results reported here indicate that the Tregs induced by orthotopic corneal allografts are remarkably different from the Tregs that are induced by AC injection of alloantigen. Although both of these Treg populations promote corneal allograft survival, they display distinctly different phenotypes. PMID:20702818

  2. Diabetic corneal neuropathy.

    PubMed Central

    Schultz, R O; Peters, M A; Sobocinski, K; Nassif, K; Schultz, K J

    1983-01-01

    Corneal epithelial lesions can be found in approximately one-half of asymptomatic patients with diabetes mellitus. These lesions are transient and clinically resemble the keratopathy seen in staphylococcal keratoconjunctivitis. Staphylococcal organisms, however, can be isolated in equal percentages from diabetic patients without keratopathy. Diabetic peripheral neuropathy was found to be related to the presence of diabetic keratopathy after adjusting for age with analysis of covariance. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than 0.01); and the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were: reduced tear breakup time (P less than 0.03), type of diabetes (P less than 0.01), and metabolic status as indicated by c-peptide fasting (P less than 0.01). No significant relationships were found between the presence of keratopathy and tear glucose levels, endothelial cell densities, corneal thickness measurements, the presence of S epidermidis, or with duration of disease. It is our conclusion that asymptomatic epithelial lesions in the nontraumatized diabetic cornea can occur as a manifestation of generalized polyneuropathy and probably represent a specific form of corneal neuropathy. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:6676964

  3. Diabetic Macular Edema

    NASA Astrophysics Data System (ADS)

    Lobo, Conceição; Pires, Isabel; Cunha-Vaz, José

    The optical coherence tomography (OCT), a noninvasive and noncontact diagnostic method, was introduced in 1995 for imaging macular diseases. In diabetic macular edema (DME), OCT scans show hyporeflectivity, due to intraretinal and/or subretinal fluid accumulation, related to inner and/or outer blood-retinal barrier breakdown. OCT tomograms may also reveal the presence of hard exudates, as hyperreflective spots with a shadow, in the outer retinal layers, among others. In conclusion, OCT is a particularly valuable diagnostic tool in DME, helpful both in the diagnosis and follow-up procedure.

  4. Magnetic Nanoparticles as a Potential Vehicle for Corneal Endothelium Repair.

    PubMed

    Cornell, Lauren E; Wehmeyer, Jenny L; Johnson, Anthony J; Desilva, Mauris N; Zamora, David O

    2016-05-01

    The corneal endothelium is paramount to the health and function of the cornea as damage to this cell layer can lead to corneal edema, opacification, and ultimately vision loss. Transplantation of the corneal endothelium is associated with numerous limitations, including graft rejection, thus an alternative therapeutic treatment is needed to restore endothelial layer integrity. We hypothesize that a nanotechnology-based approach using superparamagnetic iron oxide nanoparticles (SPIONPs) can ultimately be used to guide corneal endothelial cells (CECs) to injured areas via an external magnetic force without changing their morphology or viability. In this feasibility study we examined the effects of SPIONPs on the morphology and viability of bovine CECs in the presence of a magnetic force. The CECs were exposed to increasing SPIONP concentrations and the viability and cytoskeletal structure assessed over 3 days via metabolic analysis and rhodamine phalloidin staining. Significant differences (p < .05) in the metabolic activity of the CECs (100 × 10(6) SPIONP/cell) occurred in the presence of magnetic force versus those with no magnetic force. No differences were observed in the cytoskeleton of CECs in the presence or absence of magnetic force for all SPIONP concentrations. These SPIONPs will next be evaluated with human CECs for future applications. PMID:27168578

  5. Personalised lamellar keratoplasty and keratopigmentation in Asian corneal leucoma patients

    PubMed Central

    Liu, Xin; Shen, Jun-Hui; Zhou, Qi; Liu, Zhen-Xing; Tang, Shen-Fei; Chen, Ran-Ran; Sui, Gui-Qin; Bi, Yan-Long

    2015-01-01

    Objective: To describe a personalised lamellar keratoplasty (LK) associated with the keratopigmentation (KTP) technique for corneal leucoma among Asian patients. Methods: This report was a non-randomised, retrospective clinical study performed in 32 consecutive eyes of 32 patients to improve cosmetic appearance. Twenty-two patients underwent LK combined with KTP, either by intralamellar or superficial route. Ten patients underwent the single personalised keratopigmentation method. The subjective and objective cosmetic results, ocular irritation, colour fading, neovascularisation formation and incidence of immune rejection were evaluated until three years after surgery. Results: No complications occurred, and the corneal leucoma was successfully stained with India ink in all 32 patients. Most of the patients showed good cosmetic appearance. Pain, conjunctival congestion, corneal edema and foreign body sensation disappeared gradually within two to three weeks after surgery in all patients. Graft swelling, non-healing, or detaching was not observed during follow-up. However, two patients had slight opacity three years after LK. Colour fading was observed in one patient who underwent intralamellar corneal staining 10 months after surgery. Re-staining was performed. Conclusion: KTP combined with personalised LK is an effective personalised technique that presents long-standing colour staining and good cosmetic efficacy. PMID:26309607

  6. Diabetes aggravates nanoparticles induced breakdown of the blood-brain barrier permeability, brain edema formation, alterations in cerebral blood flow and neuronal injury. An experimental study using physiological and morphological investigations in the rat.

    PubMed

    Sharma, Hari Shanker; Patnaik, Ranjana; Sharma, Aruna

    2010-12-01

    The possibility that diabetes aggravates nanoparticles induced blood-brain barrier (BBB) breakdown, edema formation and brain pathology was examined in a rat model. Engineered nanoparticles from metals Ag and Cu (50-60 mn) were administered (50 mg/kg, i.p.) once daily for 7 days in normal and streptozotocine induced diabetic rats. On the 8th day, BBB permeability to Evans blue and radioactive iodine (131I-sodium) was examined in 16 brain regions. In these brain regions alterations in regional CBF was also evaluated using radiolabelled (125I) carbonized microspheres (o.d. 15 +/- 6 microm). Regional brain edema and Na+, K+ and Cl- ion analysis were done in 8 selected brain regions. Histopathology was used to detect neuronal damage employing Nissl staining. Nanoparticles treatment in diabetic rats showed much more profound disruption of the BBB to Evans blue albumin (EBA) and radioiodine in almost all the 16 regions examined as compared to the normal animals. In these diabetic animals reduction in regional cerebral blood flow (CBF) was more pronounced than in normal rats. Edema development as seen using water content and increase in Na+ and a decrease in K+ ion were most marked in diabetic rats as compared to normal rats after nanoparticles treatment. Cell changes in the regions of BBB disruptions were also exacerbated in diabetic rats compared to normal group after nanoparticles treatment. Taken together, these observations are the first to show that diabetic rats are more susceptible to nanoparticles induced cerebrovascular reactions in the brain and neuronal damage. The possible mechanisms and significance of the present findings are discussed. PMID:21121280

  7. Molecular pathophysiology of cerebral edema.

    PubMed

    Stokum, Jesse A; Gerzanich, Volodymyr; Simard, J Marc

    2016-03-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

  8. Molecular pathophysiology of cerebral edema

    PubMed Central

    Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

  9. THz and mm-Wave Sensing of Corneal Tissue Water Content: In Vivo Sensing and Imaging Results

    PubMed Central

    Taylor, Zachary D.; Garritano, James; Sung, Shijun; Bajwa, Neha; Bennett, David B.; Nowroozi, Bryan; Tewari, Priyamvada; Sayre, James W.; Hubschman, Jean-Pierre; Deng, Sophie X.; Brown, Elliott R.; Grundfest, Warren S.

    2015-01-01

    A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo. These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10–15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10× higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo. PMID:26161292

  10. Nanomedicine Approaches for Corneal Diseases

    PubMed Central

    Chaurasia, Shyam S.; Lim, Rayne R.; Lakshminarayanan, Rajamani; Mohan, Rajiv R.

    2015-01-01

    Corneal diseases are the third leading cause of blindness globally. Topical nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, antibiotics and tissue transplantation are currently used to treat corneal pathological conditions. However, barrier properties of the ocular surface necessitate high concentration of the drugs applied in the eye repeatedly. This often results in poor efficacy and several side-effects. Nanoparticle-based molecular medicine seeks to overcome these limitations by enhancing the permeability and pharmacological properties of the drugs. The promise of nanomedicine approaches for treating corneal defects and restoring vision without side effects in preclinical animal studies has been demonstrated. Numerous polymeric, metallic and hybrid nanoparticles capable of transporting genes into desired corneal cells to intercept pathologic pathways and processes leading to blindness have been identified. This review provides an overview of corneal diseases, nanovector properties and their applications in drug-delivery and corneal disease management. PMID:25941990

  11. Corneal Lymphangiogenesis in Herpetic Stromal Keratitis

    PubMed Central

    Park, Paul J; Chang, Michael; Garg, Nitin; Zhu, Jimmy; Chang, Jin-Hong; Shukla, Deepak

    2014-01-01

    Corneal lymphangiogenesis is the extension of lymphatic vessels into the normally alymphatic cornea, a process that compromises the cornea’s immune privileged state and facilitates herpetic stromal keratitis (HSK). HSK results most commonly from infection by herpes simplex virus-1 (HSV-1) and is characterized by immune- and inflammation-mediated damage to the deep layers of the cornea. Current research demonstrates the potential of anti-lymphangiogenic therapy to decrease and prevent herpes-induced lymphangiogenesis. PMID:25444520

  12. Thrombospondin-1 induces differential response in human corneal and conjunctival epithelial cells lines under in vitro inflammatory and apoptotic conditions.

    PubMed

    Soriano-Romaní, Laura; García-Posadas, Laura; López-García, Antonio; Paraoan, Luminita; Diebold, Yolanda

    2015-05-01

    Recently, thrombospondin-1 (TSP-1) has been reported to be critical for maintaining a healthy ocular surface. The purpose of the study was to characterize the expression of TSP-1 and of its receptors CD36 and CD47 in corneal and conjunctival epithelial cells and determine the effect of exogenous TSP-1 treatment on these cells, following the induction of inflammation- and apoptosis-related changes. The expression of TSP-1, CD36 and CD47 by corneal and conjunctival cell lines was firstly characterized by ELISA, immunofluorescence analysis, Western blotting and reverse transcription polymerase chain reaction (RT-PCR). Benzalkonium chloride (BAC) exposure for 5 or 15 min was used as pro-inflammatory and pro-apoptotic stimulus for corneal or conjunctival epithelial cells, respectively. To analyze inflammation and apoptosis-related changes, IL-6 and TGF-β2 secretion determined by ELISA was used as inflammatory markers, while activated caspase-3/7 levels and cell viability, determined by CellEvent™ Caspase-3/7 Green Detection Reagent and XTT cytotoxicity assay, respectively, were used as apoptotic markers. Changes in CD36 and CD47 mRNA expression were quantified by real time RT-PCR. Corneal epithelial cells secreted and expressed higher protein levels of TSP-1 than conjunctival epithelial cells, although TSP-1 mRNA expression levels were similar and had lower CD36 and CD47, both at protein and mRNA levels. Both cell lines responded to exogenous TSP-1 treatment increasing CD36 at protein and mRNA levels. Blocking experiments revealed a predominance of TSP-1/CD47 rather than TSP-1/CD36 interactions to up-regulate CD36 levels in conjunctival epithelial cells, but not in corneal epithelial cells. BAC exposure increased IL-6 secretion and caspase-3/7 levels and decreased cell viability in both, corneal and conjunctival epithelial cells. Moreover, BAC exposure increased latent TGF-β2 levels in conjunctival epithelial cells. Interestingly, CD36 mRNA expression was down

  13. Corneal thickness in glaucoma.

    PubMed

    De Cevallos, E; Dohlman, C H; Reinhart, W J

    1976-02-01

    The central corneal stromal thickness of patients with open angle glaucoma, secondary glaucoma (the majority aphakic), or a history of unilateral acute angle closure glaucoma were measured and compared with the stromal thickness of a group of normal patients. In open angle glaucoma, there was a small but significant increase in the average stromal thickness. This thickness increase was, in all likelihood, due to an abnormal function of the endothelium in this disease since the level of the intraocular pressure did not seem to be a factor. There was no correlation between stromal thickness and duration of the glaucoma or type of anti-glaucomatous medication. Most cases of secondary glaucome, controlled medically or not, had markedly increased corneal thickness, again, most likely, due to endothelial damage rather than to level of intraocular pressure. After an angle closure attack, permanent damage to the cornea was found to be rare. PMID:1247273

  14. Corneal Opacity in a Participant of a 161-km Mountain Bike Race at High Altitude.

    PubMed

    Khodaee, Morteza; Torres, David R

    2016-06-01

    Visual dysfunction is a relatively uncommon complaint among athletes during ultraendurance races. The pathophysiology of most of these cases is unknown. Corneal opacity has been speculated as the etiology for most of reported cases. We are presenting a case of a 56-year-old man with a partial unilateral corneal opacity and edema at kilometer 150 of a 161-km mountain bike race in high altitude. He was not able to finish the race (12-hour cutoff) because of his visual symptoms. He completely recovered in 3 days with no sequelae. PMID:27095539

  15. Diabetic Macular Edema

    PubMed Central

    Gundogan, Fatih C.; Yolcu, Umit; Akay, Fahrettin; Ilhan, Abdullah; Ozge, Gokhan; Uzun, Salih

    2016-01-01

    Diabetic macular edema (DME), one the most prevalent causes of visual loss in industrialized countries, may be diagnosed at any stage of diabetic retinopathy. The diagnosis, treatment, and follow up of DME have become straightforward with recent developments in fundus imaging, such as optical coherence tomography. Laser photocoagulation, intravitreal injections, and pars plana vitrectomy surgery are the current treatment modalities; however, the positive effects of currently available intravitreally injected agents are temporary. At this point, further treatment choices are needed for a permanent effect. Sources of data selection: The articles published between 1985-2015 years on major databases were searched and most appropriate 40 papers were used to write this review article. PMID:27182271

  16. Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome.

    PubMed

    Fuentes-Julián, Sherezade; Arnalich-Montiel, Francisco; Jaumandreu, Laia; Leal, Marina; Casado, Alfonso; García-Tuñon, Ignacio; Hernández-Jiménez, Enrique; López-Collazo, Eduardo; De Miguel, Maria P

    2015-01-01

    The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC) into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical practice. PMID

  17. Adipose-Derived Mesenchymal Stem Cell Administration Does Not Improve Corneal Graft Survival Outcome

    PubMed Central

    Fuentes-Julián, Sherezade; Arnalich-Montiel, Francisco; Jaumandreu, Laia; Leal, Marina; Casado, Alfonso; García-Tuñon, Ignacio; Hernández-Jiménez, Enrique; López-Collazo, Eduardo; De Miguel, Maria P.

    2015-01-01

    The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC) into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical practice. PMID

  18. Comparison of Cytotoxic Effects on Rabbit Corneal Endothelium between Preservative-free and Preservative-containing Dorzolamide/timolol

    PubMed Central

    Kwon, Junki; Heo, Jeong Hwa; Kim, Hyo Myung

    2015-01-01

    Purpose To evaluate and compare the toxic effects of eyedrops containing a fixed combination of 2.0% dorzolamide and 0.5% maleate timolol with or without preservatives on rabbit corneal endothelium. Methods This study was performed with 22 eyes of New Zealand white rabbits. Dorzolamide/timolol eyedrops with preservative (Cosopt group) or without preservative (Cosopt-S group) were diluted with a balanced salt solution at a 1 : 1 ratio. We injected 0.1 mL of diluted Cosopt into the anterior chamber of left eyes and an equal volume of diluted Cosopt-S into the anterior chamber of right eyes. Corneal thickness, corneal haze, and conjunctival injection were measured before and 24 hours after treatment. Endothelial damage was compared between both eyes by vital staining (alizarin red/trypan blue staining), live/dead cell assay, TUNEL assay, and scanning electron microscopy. Results Corneal endothelial damage was severe in the Cosopt group. Cosopt-treated eyes exhibited remarkable corneal edema and prominent apoptosis of endothelial cells. In addition, the live/dead cell assay revealed many dead cells in the endothelium, and scanning electron microscopy analysis showed that corneal endothelial cells exhibited a partial loss of microvilli on the surface as well as extensive destruction of intercellular junctions. However, in the Cosopt-S group, corneal edema was mild and the damage to the corneal endothelium was minimal. Conclusions The main cause of corneal endothelial toxicity was due to the preservative in the dorzolamide/timolol fixed combination eyedrops, and not the active ingredient. Thus, it appears to be safer to use preservative-free eyedrops during the early postoperative period. PMID:26457041

  19. Chronic oral or intraarticular administration of docosahexaenoic acid reduces nociception and knee edema and improves functional outcomes in a mouse model of Complete Freund’s Adjuvant–induced knee arthritis

    PubMed Central

    2014-01-01

    Introduction Clinical and preclinical studies have shown that supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs) reduce joint destruction and inflammation present in rheumatoid arthritis (RA). However, the effects of individual ω-3 PUFAs on chronic arthritic pain have not been evaluated to date. Thus, our aim in this study was to examine whether purified docosahexaenoic acid (DHA, an ω-3 PUFA) reduces spontaneous pain-related behavior and knee edema and improves functional outcomes in a mouse model of knee arthritis. Methods Unilateral arthritis was induced by multiple injections of Complete Freund’s Adjuvant (CFA) into the right knee joints of male ICR adult mice. Mice that received CFA injections were then chronically treated from day 15 until day 25 post–initial CFA injection with oral DHA (10, 30 and 100 mg/kg daily) or intraarticular DHA (25 and 50 μg/joint twice weekly). Spontaneous flinching of the injected extremity (considered as spontaneous pain-related behavior), vertical rearing and horizontal exploratory activity (considered as functional outcomes) and knee edema were assessed. To determine whether an endogenous opioid mechanism was involved in the therapeutic effect of DHA, naloxone (NLX, an opioid receptor antagonist, 3 mg/kg subcutaneously) was administered in arthritic mice chronically treated with DHA (30 mg/kg by mouth) at day 25 post–CFA injection. Results The intraarticular CFA injections resulted in increasing spontaneous flinching and knee edema of the ipsilateral extremity as well as worsening functional outcomes as time progressed. Chronic administration of DHA, given either orally or intraarticularly, significantly improved horizontal exploratory activity and reduced flinching behavior and knee edema in a dose-dependent manner. Administration of NLX did not reverse the antinociceptive effect of DHA. Conclusions To the best of our knowledge, this report is the first to demonstrate DHA’s antinociceptive and

  20. Acute Corneal Hydrops in Children with Primary Infantile Glaucoma: A Report of 31 Cases over 23 Years at the LVPEI

    PubMed Central

    Mandal, Anil K.

    2016-01-01

    Purpose Relatively little data exist regarding the outcomes of children with primary infantile glaucoma presenting with acute corneal hydrops. The aim of our study was to determine the surgical outcome of children of infantile glaucoma who presented with acute corneal hydrops. Methods In total, 38 eyes of 31 consecutive children of infantile glaucoma presented with acute corneal hydrops who underwent primary combined trabeculotomy-trabeculectomy (CTT) by a single surgeon from January 1990 to December 2012 at the LV Prasad Eye Institute (LVPEI), a tertiary eye care centre in Southern India were enrolled in this retrospective study. Primary outcome measures were intraocular pressure (IOP) control (IOP ≤ 16 mmHg under anaesthesia or IOP ≤ 21 mmHg without anaesthesia) and clearance of corneal edema. Secondary outcome measures were visual acuity (VA), corneal diameter, bleb appearance, intraoperative and postoperative complications. Results Mean age at presentation was 6.4 months (range, 2–11 months) and seven eyes (23%) had bilateral affliction. At presentation, all eyes (100%) had moderate to severe degree of corneal edema with a mean preoperative IOP of 25.6 ±5.1 mmHg. Postoperatively, the IOP reduced to 12.0 ± 3.8 mmHg (difference = -13.6, 95% CI = -15.7 to -11.5, t = -13.18, p<0.0001), and the percentage reduction in IOP was 53.05%. Preoperatively 83% of the eyes were on antiglaucoma medication, and postoperatively 2 eyes (5.3%) required 1 antiglaucoma medication for control of IOP. Preoperatively, corneal edema was present in all eyes and postoperatively it cleared in all of them. Significant myopic astigmatism was present in 28 eyes (74%), the commonest being compound myopic astigmatism (75%) followed by simple myopic astigmatism (21%). Normal VA (best-corrected VA; BCVA ≥ 20/60) was achieved in 44.4% of the eyes and 22.2% eyes had low vision (BCVA, <20/60 to 20/400). Complete success (IOP control and clearance of corneal oedema) was obtained in 94

  1. Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus

    PubMed Central

    Giordano, Carmela; Vinet, Jonathan; Curia, Giulia; Biagini, Giuseppe

    2015-01-01

    Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs. PMID:26555229

  2. Effect of glycemic control on corneal nerves and peripheral neuropathy in streptozotocin-induced diabetic C57Bl/6J mice

    PubMed Central

    Yorek, Matthew S.; Obrosov, Alexander; Shevalye, Hanna; Lupachyk, Sergey; Harper, Matthew M.; Kardon, Randy H.; Yorek, Mark A.

    2016-01-01

    We sought to determine the impact that duration of hyperglycemia and control has on corneal nerve fiber density in relation to standard diabetic neuropathy endpoints. Control and streptozotocin-diabetic C57Bl/6J mice were analyzed after 4, 8, 12 and 20 weeks. For the 20 week time point five groups of mice were compared: control, untreated diabetic, and diabetic treated with insulin designated as having either poor glycemic control, good glycemic control or poor glycemic control switched to good glycemic control. Hyperglycemia was regulated by use of insulin releasing pellets. Loss of corneal nerves in the sub-epithelial nerve plexus or corneal epithelium progressed slowly in diabetic mice requiring 20 weeks to reach statistical significance. In comparison, slowing of motor and sensory nerve conduction velocity developed rapidly with significant difference compared to control mice observed after 4 and 8 weeks of hyperglycemia, respectively. In diabetic mice with good glycemic control average blood glucose levels over the 20 week experimental period were lowered from 589 ± 2 to 251 ± 9 mg/dl. All diabetic neuropathy endpoints examined were improved in diabetic mice with good glycemic control compared to untreated diabetic mice. However, good control of blood glucose was not totally sufficient in preventing diabetic neuropathy. PMID:25403729

  3. Azithromycin (AZM) treatment increases survival of high risk corneal allotransplants

    PubMed Central

    Medina, Carlos A.; Rowe, Alexander M.; Yun, Hongmin; Knickelbein, Jared E.; Lathrop, Kira L.; Hendricks, Robert L.

    2012-01-01

    Purpose To test the therapeutic efficacy of AZM, a macrolide antibiotic for prolonging murine “high risk” corneal allograft survival. Methods Fully MHC mismatched corneas were transplanted from C57BL/6 donors to BALB/c recipients with suture-induced vascularized “high risk” corneal beds. Recipient mice were either not treated or treated with topical AZM, oral AZM, or both. Evaluation of graft vascularization and clarity was performed in masked fashion. Lymph nodes were excised and analyzed for CD4, FoxP3, and CD44 by flow cytometry; and for T cell priming by proliferation and cytokine production in mixed lymphocyte cultures. Corneal whole mounts were evaluated by confocal microscopy. Results The incidence of graft rejection in the control group (81.8%) was significantly reduced by AZM treatment (18.2% topical, 21.7% oral, 33.3% topical + oral), although corneal vascularization was not affected by treatment. The frequency of corneas that retained complete clarity following transplantation was higher in the AZM treated groups. Reduced graft rejection in the AZM treated groups was not associated with a reduced allospecific T cell response or increased frequency of T regulatory cells. Conclusions AZM is effective in prolonging survival of “high risk” corneal allografts by an as yet undefined mechanism that does not appear to involve modulation of corneal neovascularization or allo-specific T cell priming. PMID:23407315

  4. Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis.

    PubMed

    Connor, Alicia L; Kelley, Philip M; Tempero, Richard M

    2016-03-01

    Postnatal inflammatory lymphangiogenesis presumably requires precise regulatory processes to properly assemble proliferating lymphatic endothelial cells (LECs). The specific mechanisms that regulate the assembly of LECs during new lymphatic vessel synthesis are unclear. Dynamic endothelial shuffling and rearrangement has been proposed as a mechanism of blood vessel growth. We developed genetic lineage-tracing strategies using an inductive transgenic technology to track the fate of entire tandem dimer tomato-positive (tdT) lymphatic vessels or small, in some cases clonal, populations of LECs. We coupled this platform with a suture-induced mouse model of corneal lymphangiogenesis and used different analytic microscopy techniques including serial live imaging to study the spatial properties of proliferating tdT(+) LEC progenies. LEC precursors and their progeny expanded from the corneal limbal lymphatic vessel and were assembled contiguously to comprise a subunit within a new lymphatic vessel. VE-cadherin blockade induced morphologic abnormalities in newly synthesized lymphatic vessels, but did not disrupt the tdT(+) lymphatic endothelial lineage assembly. Analysis of this static and dynamic data based largely on direct in vivo observations supports a model of lymphatic endothelial lineage assemblage during corneal inflammatory lymphangiogenesis. PMID:26658452

  5. Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis

    PubMed Central

    Connor, Alicia L.; Kelley, Philip M.; Tempero, Richard M.

    2015-01-01

    Post natal inflammatory lymphangiogenesis presumably requires precise regulatory processes to properly assemble proliferating lymphatic endothelial cells (LECs). The specific mechanisms that regulate the assembly of LECs during new lymphatic vessel synthesis are unclear. Dynamic endothelial shuffling and rearrangement has been proposed as a mechanism of blood vessel growth. We developed genetic lineage tracing strategies using an inductive transgenic technology to track the fate of entire tandem dimer tomato positive (tdT) lymphatic vessels or small, in some cases clonal, populations of LECs. We coupled this platform with a suture induced mouse model of corneal lymphangiogenesis and used different analytic microscopy techniques including serial live imaging to study the spatial properties of proliferating tdT+ LEC progenies. LEC precursors and their progeny expanded from the corneal limbal lymphatic vessel and were assembled contiguously to comprise a subunit within a new lymphatic vessel. VE-cadherin blockade induced morphologic abnormalities in newly synthesized lymphatic vessels, but did not disrupt the tdT+ lymphatic endothelial lineage assembly. Analysis of this static and dynamic data based largely on direct in vivo observations supports a model of lymphatic endothelial lineage assemblage during corneal inflammatory lymphangiogenesis. PMID:26658452

  6. Corneal Aberrations Before and After Photorefractive Keratectomy

    PubMed Central

    Rosa, Nicola; De Bernardo, Maddalena; Lanza, Michele; Borrelli, Maria; Fusco, Fabrizia; Flagiello, Antimo

    2010-01-01

    Purpose To determine whether - and which - higher-order corneal aberrations, up to the sixth order, are induced by photorefractive keratectomy (PRK). Methods 197 eyes of 197 patients have been examined with a corneal aberrometer for a 3.5 and a 6.0 mm pupil simulation, both before and 1, 3, 6 months after myopic PRK treatment ranging from −15.25 D to -0.5 D (mean −5.31±2.95 D). The statistical evaluation was performed using a paired Student's T-test. Results After PRK there is a clear-cut increase in almost all the higher-order corneal aberrations for both a 3.5 and a 6.0 mm pupil simulation. These aberrations tend to normalize after 3 and 6 months mainly for a 3.5 mm simulation, whereas such normalization is not present for a 6.0 mm simulation. Conclusions PRK induces significant aberrations both for 3.5 and 6 mm pupils, 1 month after PRK, but a trend towards normalization is evident at the 6 month follow-up for the smaller pupil size.

  7. In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition.

    PubMed

    Ho, Wei-Ting; Su, Chien-Chia; Chang, Jung-Shen; Chang, Shu-Wen; Hu, Fung-Rong; Jou, Tzuu-Shuh; Wang, I-Jong

    2016-01-01

    Corneal endothelial cells (CECs) play a crucial role in maintaining corneal clarity through active pumping. A reduced CEC count may lead to corneal edema and diminished visual acuity. However, human CECs are prone to compromised proliferative potential. Furthermore, stimulation of cell growth is often complicated by gradual endothelial-mesenchymal transition (EnMT). Therefore, understanding the mechanism of EnMT is necessary for facilitating the regeneration of CECs with competent function. In this study, we prepared a primary culture of bovine CECs by peeling the CECs with Descemet's membrane from the corneal button and demonstrated that bovine CECs exhibited the EnMT process, including phenotypic change, nuclear translocation of β-catenin, and EMT regulators snail and slug, in the in vitro culture. Furthermore, we used a rat corneal endothelium cryoinjury model to demonstrate the EnMT process in vivo. Collectively, the in vitro primary culture of bovine CECs and in vivo rat corneal endothelium cryoinjury models offers useful platforms for investigating the mechanism of EnMT. PMID:27583795

  8. Influenza leaves a TRAIL to pulmonary edema.

    PubMed

    Brauer, Rena; Chen, Peter

    2016-04-01

    Influenza infection can cause acute respiratory distress syndrome (ARDS), leading to poor disease outcome with high mortality. One of the driving features in the pathogenesis of ARDS is the accumulation of fluid in the alveoli, which causes severe pulmonary edema and impaired oxygen uptake. In this issue of the JCI, Peteranderl and colleagues define a paracrine communication between macrophages and type II alveolar epithelial cells during influenza infection where IFNα induces macrophage secretion of TRAIL that causes endocytosis of Na,K-ATPase by the alveolar epithelium. This reduction of Na,K-ATPase expression decreases alveolar fluid clearance, which in turn leads to pulmonary edema. Inhibition of the TRAIL signaling pathway has been shown to improve lung injury after influenza infection, and future studies will be needed to determine if blocking this pathway is a viable option in the treatment of ARDS. PMID:26999598

  9. The evolution of scuba divers pulmonary edema.

    PubMed

    Edmonds, Carl

    2016-01-01

    The evolution of scuba divers pulmonary edema is described. When discovered in 1981, it was believed to be a cold-induced response in a submerged, otherwise healthy, scuba diver. The clinical features are described and discussed, as are the demographics. An alleged prevalence of 1.1% was complicated by problematic statistics and an apparent increase in reported cases. Recurrences both while diving and swimming or snorkeling were common. More recent case reports and surveys are described, identifying predisposing factors and associations, including cardiac pathology. Stress cardiomyopathies, reversible myocardial disorder or Takotsubo cardiomyopathy, may complicate the presentation, especially in older females. Relevant cardiac investigations and autopsy findings are reviewed. Disease severity and potential lethality of scuba divers pulmonary edema became more apparent early this century, and these influence our current recommendations to survivors. First aid and treatment are also discussed. PMID:27265985

  10. Human excimer laser corneal surgery: preliminary report.

    PubMed Central

    L'Esperance, F A; Taylor, D M; Del Pero, R A; Roberts, A; Gigstad, J; Stokes, M T; Warner, J W; Telfair, W B; Martin, C A; Yoder, P R

    1988-01-01

    The first human trial utilizing the argon fluoride excimer laser at 193 nm to produce a superficial keratectomy in ten human eyes has been described with the histopathological evaluation of four eyes and the longer gross appearance of six eyes at intervals extending to 10 months post-excimer laser treatment. The process of laser superficial keratectomy has proved to be one of the promising areas of surgical intervention for reconstructive or refractive keratoplasty in the future. Intensive investigations need to be undertaken on the corneal wound healing process following laser ablation as well as the nature, and long-term stability of the corneal excisions or induced refractive corrections. It is essential that the optimal laser parameters be established for the various refractive corrections and other corneal surgical techniques, and that pathophysiologic and histopathologic changes that have been induced by the excimer laser-corneal tissue interaction in animals and humans be critically and extensively analyzed. Images FIGURE 1 FIGURE 19 A FIGURE 19 B FIGURE 20 A FIGURE 20 B FIGURE 21 A FIGURE 21 B FIGURE 22 A FIGURE 22 B FIGURE 23 FIGURE 24 FIGURE 25 FIGURE 26 FIGURE 27 FIGURE 28 FIGURE 29 A FIGURE 29 B FIGURE 29 C FIGURE 29 D FIGURE 30 A FIGURE 30 B FIGURE 31 A FIGURE 31 B FIGURE 32 FIGURE 33 FIGURE 34 FIGURE 35 FIGURE 36 FIGURE 37 A FIGURE 37 B FIGURE 37 C FIGURE 38 A FIGURE 38 B FIGURE 39 A FIGURE 39 B FIGURE 39 C FIGURE 40 A FIGURE 40 B PMID:2979049

  11. Corneal amyloidosis associated with keratoconus.

    PubMed

    Stern, G A; Knapp, A; Hood, C I

    1988-01-01

    Nodular, gray-white, central corneal opacities which extended from the subepithelial zone through the anterior four fifths of the stroma developed in a 50-year-old man with a longstanding history of hard contact lens wear for keratoconus. Results of histopathologic analysis of the corneal button obtained at the time of penetrating keratoplasty disclosed that the opacities were composed of amyloid. Corneal amyloidosis is rarely found in association with keratoconus. Although there were some similarities in the pattern of amyloid deposition to that seen in primary familial amyloidosis of the cornea, the authors believe that their patient is more likely to have had a secondary amyloidosis. Corneal amyloidosis should be considered in keratoconus patients with development of unusual forms of central corneal opacification. PMID:3278260

  12. Early Events in the Amyloid Formation of the A546T Mutant of Transforming Growth Factor Beta Induced Protein (TGFBIp) in Corneal Dystrophies Compared to the Non-Fibrillating R555W and R555Q Mutants

    PubMed Central

    Koldsø, Heidi; Andersen, Ole Juul; Nikolajsen, Camilla Lund; Scavenius, Carsten; Sørensen, Charlotte S.; Underhaug, Jarl; Runager, Kasper; Nielsen, Niels Chr.; Enghild, Jan J.; Schiøtt, Birgit

    2016-01-01

    The human transforming growth factor beta induced protein (TGFBIp) is involved in several types of corneal dystrophies where protein aggregation and amyloid fibril formation severely impairs vision. Most disease-causing mutations are located in the last of four homologous fasciclin-1 (FAS1) domains of the protein, and it has been shown that when isolated, the fourth FAS1 domain (FAS1–4) mimics the behavior of full-length TGFBIp. In this study, we use molecular dynamics simulations and principal component analysis to study the wild type FAS1–4 domain along with three disease-causing mutations (R555W, R555Q, and A546T) to decipher any internal difference in dynamical properties of the domains that may explain their varied stabilities and aggregation properties. In addition, we use a protein-protein docking method in combination with chemical cross-linking experiments and mass spectrometry of the cross-linked species to obtain information about interaction faces between identical FAS1–4 domains. The results show that the pathogenic mutations A546T and R555W affect the packing in the hydrophobic core of FAS1–4 in different directions. We further show that the FAS1–4 monomers associate using their β-rich regions consistent with peptides observed to be part of the amyloid fibril core in lattice corneal dystrophy patients. PMID:26305369

  13. Corneal seal device

    NASA Technical Reports Server (NTRS)

    Baehr, E. F. (Inventor)

    1977-01-01

    A corneal seal device is provided which, when placed in an incision in the eye, permits the insertion of a surgical tool or instrument through the device into the eye. The device includes a seal chamber which opens into a tube which is adapted to be sutured to the eye and serves as an entry passage for a tool. A sealable aperture in the chamber permits passage of the tool through the chamber into the tube and hence into the eye. The chamber includes inlet ports adapted to be connected to a regulated source of irrigation fluid which provides a safe intraocular pressure.

  14. Corticosteroid-loaded biodegradable nanoparticles for prevention of corneal allograft rejection in rats.

    PubMed

    Pan, Qing; Xu, Qingguo; Boylan, Nicholas J; Lamb, Nicholas W; Emmert, David G; Yang, Jeh-Chang; Tang, Li; Heflin, Tom; Alwadani, Saeed; Eberhart, Charles G; Stark, Walter J; Hanes, Justin

    2015-03-10

    Immunologic graft rejection is one of the main causes of short and long-term graft failure in corneal transplantation. Steroids are the most commonly used immunosuppressive agents for postoperative management and prevention of corneal graft rejection. However, steroids delivered in eye drops are rapidly cleared from the surface of the eye, so the required frequency of dosing for corneal graft rejection management can be as high as once every 2h. Additionally, these eye drops are often prescribed for daily use for 1 year or longer, which can result in poor patient compliance and steroid-related side effects. Here, we report a biodegradable nanoparticle system composed of Generally Regarded as Safe (GRAS) materials that can provide sustained release of corticosteroids to prevent corneal graft rejection following subconjunctival injection provided initially during transplant surgery. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing dexamethasone sodium phosphate (DSP) exhibited a size of 200 nm, 8 wt.% drug loading, and sustained drug release over 15 days in vitro under sink conditions. DSP-loaded nanoparticles provided sustained ocular drug levels for at least 7 days after subconjunctival administration in rats, and prevented corneal allograft rejection over the entire 9-week study when administered weekly. In contrast, control treatment groups that received weekly injections of either placebo nanoparticles, saline, or DSP in solution demonstrated corneal graft rejection accompanied by severe corneal edema, neovascularization and opacity that occurred in ≤ 4 weeks. Local controlled release of corticosteroids may reduce the rate of corneal graft rejection, perhaps especially in the days immediately following surgery when risk of rejection is highest and when typical steroid eye drop administration requirements are particularly onerous. PMID:25576786

  15. The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns.

    PubMed

    Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

    2016-01-01

    The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties. PMID:27057279

  16. Corneal structure and transparency

    PubMed Central

    Meek, Keith M.; Knupp, Carlo

    2015-01-01

    The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. PMID:26145225

  17. Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

    PubMed Central

    Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

    2012-01-01

    Purpose. The aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro. Methods. Thy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Wide-field stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth. Results. BAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P < 0.05). These changes were most significant after 0.1% BAK treatment. The extent of inflammatory cell infiltration in the cornea showed a significant negative correlation with NFD. Sequential in vivo imaging of corneas showed two forms of BAK-induced neurotoxicity: reversible neurotoxicity characterized by axonopathy and recovery, and irreversible neurotoxicity characterized by nerve degeneration and regeneration. Increased abundance of beta III tubulin in corneal lysates confirmed regeneration. A dose-related significant reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001). Conclusion. Topical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous

  18. In Vitro Expansion of Corneal Endothelial Cells on Biomimetic Substrates

    PubMed Central

    Palchesko, Rachelle N.; Lathrop, Kira L.; Funderburgh, James L.; Feinberg, Adam W.

    2015-01-01

    Corneal endothelial (CE) cells do not divide in vivo, leading to edema, corneal clouding and vision loss when the density drops below a critical level. The endothelium can be replaced by transplanting allogeneic tissue; however, access to donated tissue is limited worldwide resulting in critical need for new sources of corneal grafts. In vitro expansion of CE cells is a potential solution, but is challenging due to limited proliferation and loss of phenotype in vitro via endothelial to mesenchymal transformation (EMT) and senescence. We hypothesized that a bioengineered substrate recapitulating chemo-mechanical properties of Descemet's membrane would improve the in vitro expansion of CE cells while maintaining phenotype. Results show that bovine CE cells cultured on a polydimethylsiloxane surface with elastic modulus of 50 kPa and collagen IV coating achieved >3000-fold expansion. Cells grew in higher-density monolayers with polygonal morphology and ZO-1 localization at cell-cell junctions in contrast to control cells on polystyrene that lost these phenotypic markers coupled with increased α-smooth muscle actin expression and fibronectin fibril assembly. In total, these results demonstrate that a biomimetic substrate presenting native basement membrane ECM proteins and mechanical environment may be a key element in bioengineering functional CE layers for potential therapeutic applications. PMID:25609008

  19. [Corneal metabolism with contact lenses in competitive sports].

    PubMed

    Schnell, D; Khaireddin, R

    2013-06-01

    The corneal metabolism during the use of contact lenses plays an important role for permanent corneal health, especially in competitive sports. Thus, it is important to understand the steps of corneal metabolism in general and during highly competitive sports activity in particular. The aim of this review is to summarize the current knowledge on physiological and biochemical effects of contact lens wear. Of the energy requirements of the cornea 75 % is supplied by aerobic processes; therefore, the eye needs the highest possible amount of oxygen and sufficient glucose which can be obtained from external air and to a lesser degree from within the anterior chamber. If the oxygen supply is too low this results in hypoxic edema. Fitting athletes with contact lenses must still be viewed with caution as the visual needs of athletes are usually much more demanding than those of the general public. An indiscriminate choice of lens design can adversely affect athletic performance and may even create a hazardous situation. An intelligent choice of contact lens can provide some subtle advantages that may improve athletic performance and provide the decisive margin for victory. PMID:23783993

  20. Corneal blindness: a global perspective.

    PubMed Central

    Whitcher, J. P.; Srinivasan, M.; Upadhyay, M. P.

    2001-01-01

    Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance. The epidemiology of corneal blindness is complicated and encompasses a wide variety of infectious and inflammatory eye diseses that cause corneal scarring, which ultimately leads to functional blindness. In addition, the prevalence of corneal disease varies from country to country and even from one population to another. While cataract is responsible for nearly 20 million of the 45 million blind people in the world, the next major cause is trachoma which blinds 4.9 million individuals, mainly as a result of corneal scarring and vascularization. Ocular trauma and corneal ulceration are significant causes of corneal blindness that are often underreported but may be responsible for 1.5-2.0 million new cases of monocular blindness every year. Causes of childhood blindness (about 1.5 million worldwide with 5 million visually disabled) include xerophthalmia (350,000 cases annually), ophthalmia neonatorum, and less frequently seen ocular diseases such as herpes simplex virus infections and vernal keratoconjunctivitis. Even though the control of onchocerciasis and leprosy are public health success stories, these diseases are still significant causes of blindness--affecting a quarter of a million individuals each. Traditional eye medicines have also been implicated as a major risk factor in the current epidemic of corneal ulceration in developing countries. Because of the difficulty of treating corneal blindness once it has occurred, public health prevention programmes are the most cost-effective means of decreasing the global burden of corneal blindness. PMID:11285665

  1. Study of light scattering and transparency in human edematous corneas and application to corneal grafts

    NASA Astrophysics Data System (ADS)

    Marciano, Tal; Peyrot, Donald; Crotti, Caroline; Alahyane, Fatima; Kowalczuk, Laura; Plamann, Karsten

    2011-07-01

    The optical properties of the cornea have been a research subject of great interest for many years. Several early theories have been put forward to explain with more or less success the optical transparency of this tissue, but it was not until Maurice demonstrated in a very elegant way during the 50s that this optical transparency could be explained by the regular ultrastructure of the cornea. When becoming edematous, the cornea's ultrastructure is perturbed and the tissue becomes a strongly scattering medium. With the emergence of ophthalmologic surgery by ultrashort pulse lasers in recent years, a regain of interest in the subject of corneal transparency arose. However, relatively little and no recent data of transparency spectra measurements covering a large wavelength range is available in the literature. The purpose of this study is to provide quantitative values for light scattering and its relation to the degree of edema by measuring the spectrum of transmitted light through corneas presenting different degrees of edema. This paper focus on the comparison of laboratory measurements published earlier with a new simple method we propose We also for eye banks to quantitatively measure the degree of transparency of corneal grafts by measuring the modulation transfer function of a Siemens star viewed through a corneal graft. Indeed, there is no current method to determine the transparency of corneal graft but the subjectivity of the laboratory technician or the ophthalmic surgeon.

  2. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures. PMID:18375722

  3. Aloe vera gel facilitates re-epithelialization of corneal alkali burn in normal and diabetic rats

    PubMed Central

    Atiba, Ayman; Wasfy, Tamer; Abdo, Walied; Ghoneim, Ahmed; Kamal, Tarek; Shukry, Mustafa

    2015-01-01

    Purpose To investigate the efficacy of topical applied aloe vera (AV) and to facilitate the repair of the standardized alkaline corneal ulcer in normal and diabetic rats. Materials and methods The corneal alkali-burn injury model was established unilaterally in Wistar rats by filter paper saturated with 0.01 M NaOH contacting the eyes for 45 seconds. Rats were divided into four groups: normal control (NC), normal AV (NAV), diabetic control (DC), and diabetic AV (DAV). NAV and DAV groups were treated with AV gel eye drops four times daily, and NC and DC groups were treated with normal saline for 3 days. Corneal epithelial wound closure and degree of edema were recorded using slit lamp and optical coherence tomography at 0, 24, 48, and 72 hours postwounding. Histological examination was conducted to evaluate the degree of inflammation and the healing effect. Results Corneal epithelial wound healing was better in the NAV group than in the NC group, and it was significantly higher in the DAV group than in the DC group (P<0.05). In comparison to the DC group, DAV treated with AV demonstrated a marked reduction in edema at 48 and 72 hours. Histologically, corneal re-epithelialization was complete and higher in DAV group than that in DC group; moreover, the inflammatory cells were increased in DC group than DAV group (P<0.05). Conclusion This study demonstrated the efficacy of AV for enhanced corneal re-epithelialization, as well as reduced inflammatory response after alkali burn in rats; therefore, it could be useful as a therapy for diabetic keratopathy. PMID:26604672

  4. Management of advanced corneal ectasias.

    PubMed

    Maharana, Prafulla K; Dubey, Aditi; Jhanji, Vishal; Sharma, Namrata; Das, Sujata; Vajpayee, Rasik B

    2016-01-01

    Corneal ectasias include a group of disorders characterised by progressive thinning, bulging and distortion of the cornea. Keratoconus is the most common disease in this group. Other manifestations include pellucid marginal degeneration, Terrien's marginal degeneration, keratoglobus and ectasias following surgery. Advanced ectasias usually present with loss of vision due to high irregular astigmatism. Management of these disorders is difficult due to the peripheral location of ectasia and associated severe corneal thinning. Newer contact lenses such as scleral lenses are helpful in a selected group of patients. A majority of these cases requires surgical intervention. This review provides an update on the current treatment modalities available for management of advanced corneal ectasias. PMID:26294106

  5. Glycolic acid inhibits enzymatic, hemorrhagic and edema-inducing activities of BaP1, a P-I metalloproteinase from Bothrops asper snake venom: insights from docking and molecular modeling.

    PubMed

    Pereañez, Jaime Andrés; Patiño, Arley Camilo; Rey-Suarez, Paola; Núñez, Vitelbina; Henao Castañeda, Isabel Cristina; Rucavado, Alexandra

    2013-09-01

    Glycolic acid (GA) (2-Hydroxyethanoic acid) is widely used as chemical peeling agent in Dermatology and, more recently, as a therapeutic and cosmetic compound in the field of skin care and disease treatment. In this work we tested the inhibitory ability of glycolic acid on the enzymatic, hemorrhagic and edema-inducing activities of BaP1, a P-I metalloproteinase from Bothrops asper venom, which induces a variety of toxic actions. Glycolic acid inhibited the proteolytic activity of BaP1 on azocasein, with an IC₅₀ of 1.67 mM. The compound was also effective at inhibiting the hemorrhagic activity of BaP1 in skin and muscle in experiments involving preincubation of enzyme and inhibitor prior to injection. When BaP1 was injected i.m. and then, at the same site, different concentrations of glycolic acid were administered at either 0 or 5 min, 7 mM solutions of the inhibitor partially abrogated hemorrhagic activity when administered at 0 min. Moreover, glycolic acid inhibited, in a concentration-dependent manner, edema-forming activity of BaP1 in the footpad. In order to have insights on the mode of action of glycolic acid, UV-vis and intrinsic fluorescence studies were performed. Results of these assays suggest that glycolic acid interacts directly with BaP1 and chelates the Zn²⁺ ion at the active site. These findings were supported by molecular docking results, which suggested that glycolic acid forms hydrogen bonds with residues Glu143, Arg110 and Ala111 of the enzyme. Additionally, molecular modeling results suggest that the inhibitor chelates Zn²⁺, with a distance of 3.58 Å, and may occupy part of substrate binding cleft of BaP1. Our results suggest that glycolic acid is a candidate for the development of inhibitors to be used in snakebite envenomation. PMID:23726855

  6. Dosimetric Predictors of Laryngeal Edema

    SciTech Connect

    Sanguineti, Giuseppe . E-mail: gisangui@utmb.edu; Adapala, Prashanth; Endres, Eugene J. C; Brack, Collin; Fiorino, Claudio; Sormani, Maria Pia; Parker, Brent

    2007-07-01

    Purpose: To investigate dosimetric predictors of laryngeal edema after radiotherapy (RT). Methods and Materials: A total of 66 patients were selected who had squamous cell carcinoma of the head and neck with grossly uninvolved larynx at the time of RT, no prior major surgical operation except for neck dissection and tonsillectomy, treatment planning data available for analysis, and at least one fiberoptic examination of the larynx within 2 years from RT performed by a single observer. Both the biologically equivalent mean dose at 2 Gy per fraction and the cumulative biologic dose-volume histogram of the larynx were extracted for each patient. Laryngeal edema was prospectively scored after treatment. Time to endpoint, moderate or worse laryngeal edema (Radiation Therapy Oncology Group Grade 2+), was calculated with log rank test from the date of treatment end. Results: At a median follow-up of 17.1 months (range, 0.4- 50.0 months), the risk of Grade 2+ edema was 58.9% {+-} 7%. Mean dose to the larynx, V30, V40, V50, V60, and V70 were significantly correlated with Grade 2+ edema at univariate analysis. At multivariate analysis, mean laryngeal dose (continuum, hazard ratio, 1.11; 95% confidence interval, 1.06-1.15; p < 0.001), and positive neck stage at RT (N0-x vs. N +, hazard ratio, 3.66; 95% confidence interval, 1.40-9.58; p = 0.008) were the only independent predictors. Further stratification showed that, to minimize the risk of Grade 2+ edema, the mean dose to the larynx has to be kept {<=}43.5 Gy at 2 Gy per fraction. Conclusion: Laryngeal edema is strictly correlated with various dosimetric parameters; mean dose to the larynx should be kept {<=}43.5 Gy.

  7. [CYSTEAMINE-INDUCED MODIFICATION OF CYTOGENETIC DAMAGES TO THE CORNEAL EPITHELIUM OF MICE EXPOSED TO CORPUSCULAR RADIATION WITH VARYING LINEAR TRANSFER ENERGIES].

    PubMed

    Vorozhtsova, S V; Bulynina, T M; Molokanov, A G; Ivanov, A A

    2015-01-01

    Cytogenetic damages to cells of the corneal epithelium were studied in mice exposed to protons (10, 25, 50 and 645 MeV), ions of boron, carbon and neon, and X-rays (180 keV) within the dose range from 25 to 750 cGy and injected with a radioprotector. Animals were subjected to a single exposure. The protective effect of β-mercaptoethylamine was tested in the experiment. The radioprotector (0.2 ml) was introduced intraperitoneally 30 minutes before exposure in 350 mI/kg dose. Control animals received the same amount of sodium chloride solution. The animals were sacrificed by cervical dislocation in 24 and 72 hrs. after exposure. It was shown that cysteamine effectively protects in vivo corneal epithelium cells of mice exposed to electromagnetic radiation or protons in a broad energy spectrum (10 to 645 MeV), and to a broad range of radiation doses (25 to 750 cGy), as judged from levels of aberrant mitosis and mitotic activity. The radioprotector exhibited the highest effectiveness in animals exposed to the doses of 50 to 300 cGy. These findings prove that cysteamine may potentially be used for pharmacological protection from protons. The radioprotector failed to prevent chromosomal aberrations after exposure to heavy charged particles of boron, carbon and neon, which implies the need to design radioprotectors against this type of corpuscular radiation specifically. PMID:26292425

  8. Morphological Changes of Human Corneal Endothelial Cells after Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) Administration: A Prospective Open-Label Clinical Study

    PubMed Central

    Okumura, Naoki; Suganami, Hideki; Kinoshita, Shigeru

    2015-01-01

    Purpose To investigate the effect and safety of a selective Rho kinase inhibitor, ripasudil 0.4% eye drops, on corneal endothelial cells of healthy subjects. Design Prospective, interventional case series. Methods In this study, 6 healthy subjects were administered ripasudil 0.4% in the right eye twice daily for 1 week. Morphological changes and corneal endothelial cell density were examined by noncontact and contact specular microscopy. Central corneal thickness and corneal volume of 5 mm-diameter area of center cornea were analyzed by Pentacam Scheimpflug topography. All the above measurements were conducted in both eyes before administration, 1.5 and 6 hours after the initial administration on day 0; and in the same manner after the final administration on day 7. Results By noncontact specular microscopy, indistinct cell borders with pseudo guttae were observed, but by contact specular microscopy, morphological changes of corneal endothelial cells were mild and pseudo guttae was not observed after single and repeated administration of ripasudil in all subjects. These changes resolved prior to the next administration, and corneal endothelial cell density, central corneal thickness and corneal volume were not changed throughout the study period. Conclusion Transient morphological changes of corneal endothelial cells such as indistinct cell borders with pseudo guttae were observed by noncontact specular microscopy in healthy subjects after ripasudil administration. Corneal edema was not observed and corneal endothelial cell density did not decrease after 1 week repetitive administration. These morphological changes were reversible and corneal endothelial cell morphology returned to normal prior to the next administration. Trial Registration JAPIC Clinical Trials Information 142705 PMID:26367375

  9. Corneal Transplantation and Immune Privilege

    PubMed Central

    Niederkorn, Jerry Y.

    2013-01-01

    Corneal transplants have been successfully performed in human subjects for over 100 years and enjoy an immune privilege that is unrivaled in the field of transplantation. Immune privilege is defined as the reduced incidence and tempo in the immune rejection of corneal allografts compared to other categories of organ allografts performed under the same conditions. Skin allografts transplanted across various MHC or minor histocompatibility barriers undergo rejection in approximately 100% of the hosts. By contrast, orthotopic corneal allografts experience long-term survival in 50% to >90% of the hosts, depending on the histocompatibility barriers that confront the host. The capacity of corneal allografts to evade immune rejection is attributable to multiple anatomical, physiological, and immunoregulatory conditions that conspire to prevent the induction and expression of alloimmunity. PMID:23360158

  10. Corneal Collagen Cross-Linking

    PubMed Central

    Jankov II, Mirko R.; Jovanovic, Vesna; Nikolic, Ljubisa; Lake, Jonathan C.; Kymionis, Georgos; Coskunseven, Efekan

    2010-01-01

    Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) is a new technique of corneal tissue strengthening by using riboflavin as a photosensitizer and UVA to increase the formation of intra and interfibrillar covalent bonds by photosensitized oxidation. Keratocyte apoptosis in the anterior segment of the corneal stroma all the way down to a depth of about 300 microns has been described and a demarcation line between the treated and untreated cornea has been clearly shown. It is important to ensure that the cytotoxic threshold for the endothelium has not been exceeded by strictly respecting the minimal corneal thickness. Confocal microscopy studies show that repopulation of keratocytes is already visible 1 month after the treatment, reaching its pre-operative quantity and quality in terms of functional morphology within 6 months after the treatment. The major indication for the use of CXL is to inhibit the progression of corneal ectasias, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photoablation. This treatment has also been used to treat infectious corneal ulcers with apparent favorable results. Combination with other treatments, such as intracorneal ring segment implantation, limited topography-guided photoablation and conductive keratoplasty have been used with different levels of success. PMID:20543933

  11. Contact lens related corneal ulcer.

    PubMed

    Loh, Ky; Agarwal, P

    2010-01-01

    A corneal ulcer caused by infection is one of the major causes of blindness worldwide. One of the recent health concerns is the increasing incidence of corneal ulcers associated with contact lens user especially if the users fail to follow specific instruction in using their contact lenses. Risk factors associated with increased risk of contact lens related corneal ulcers are: overnight wear, long duration of continuous wear, lower socio-economic classes, smoking, dry eye and poor hygiene. The presenting symptoms of contact lens related corneal ulcers include eye discomfort, foreign body sensation and lacrimation. More serious symptoms are redness (especially circum-corneal injection), severe pain, photophobia, eye discharge and blurring of vision. The diagnosis is established by a thorough slit lamp microscopic examination with fluorescein staining and corneal scraping for Gram stain and culture of the infective organism. Delay in diagnosing and treatment can cause permanent blindness, therefore an early referral to ophthalmologist and commencing of antimicrobial therapy can prevent visual loss. PMID:25606178

  12. Effects of Chloride Flux Modulators in an in Vitro-model of Brain Edema Formation

    PubMed Central

    Kumar, Vikas; Naik, Runa S.; Hillert, Markus; Klein, Jochen

    2006-01-01

    Brain edema is a serious consequence of hemispheric stroke and traumatic brain injury and contributes significantly to patient mortality. In the present study, we measured water contents in hippocampal slices as an in vitro-model of edema formation. Excitotoxic conditions induced by N-methyl-d-aspartate (NMDA, 300 μM), as well as ischemia induced by oxygen-glucose deprivation (OGD) caused cellular edema formation as indicated by an increase of slice water contents. In the presence of furosemide, an inhibitor of the Na,K,Cl-cotransporter, NMDA-induced edema were reduced by 64% while OGD-induced edema were unaffected. The same observation, i.e. reduction of excitotoxic edema formation but no effect on ischemia-induced edema, was made with chloride transport inhibitors such as DIDS and niflumic acid. Under ischemic conditions, modulation of GABAA receptors by bicuculline, a GABA antagonist, or by diazepam, a GABAergic agonist, did not significantly affect edema formation. Further experiments demonstrated that low chloride conditions prevented NMDA-induced, but not OGD-induced water influx. Omission of calcium ions had no effect. Our results show that NMDA-induced edema formation is highly dependent on chloride influx as it was prevented by low-chloride conditions and by various compounds that interfere with chloride influx. In contrast, OGD-induced edema observed in brain slices were not affected by modulators of chloride fluxes. The results are discussed with reference to ionic changes occurring during tissue ischemia. Section: Neurophysiology, Neuropharmacology and other forms of Intercellular Communication. PMID:17014830

  13. Airway surface liquid volume expansion induces rapid changes in amiloride-sensitive Na+ transport across upper airway epithelium-Implications concerning the resolution of pulmonary edema

    PubMed Central

    Azizi, Fouad; Arredouani, Abdelilah; Mohammad, Ramzi M

    2015-01-01

    During airway inflammation, airway surface liquid volume (ASLV) expansion may result from the movement of plasma proteins and excess liquid into the airway lumen due to extravasation and elevation of subepithelial hydrostatic pressure. We previously demonstrated that elevation of submucosal hydrostatic pressure increases airway epithelium permeability resulting in ASLV expansion by 500 μL cm−2 h−1. Liquid reabsorption by healthy airway epithelium is regulated by active Na+ transport at a rate of 5 μL cm−2 h−1. Thus, during inflammation the airway epithelium may be submerged by a large volume of luminal liquid. Here, we have investigated the mechanism by which ASLV expansion alters active epithelial Na+ transport, and we have characterized the time course of the change. We used primary cultures of tracheal airway epithelium maintained under air interface (basal ASLV, depth is 7 ± 0.5 μm). To mimic airway flooding, ASLV was expanded to a depth of 5 mm. On switching from basal to expanded ASLV conditions, short-circuit current (Isc, a measure of total transepithelial active ion transport) declined by 90% with a half-time (t1/2) of 1 h. 24 h after the switch, there was no significant change in ATP concentration nor in the number of functional sodium pumps as revealed by [3H]-ouabain binding. However, amiloride-sensitive uptake of 22Na+ was reduced by 70% upon ASLV expansion. This process is reversible since after returning cells back to air interface, Isc recovered with a t1/2 of 5–10 h. These results may have important clinical implications concerning the development of Na+ channels activators and resolution of pulmonary edema. PMID:26333829

  14. Biomechanical properties of corneal tissue after ultraviolet-A-riboflavin crosslinking.

    PubMed

    Beshtawi, Ithar M; O'Donnell, Clare; Radhakrishnan, Hema

    2013-03-01

    Photodynamic collagen crosslinking (CXL) using ultraviolet-A (UVA) irradiation combined with the photosensitizer riboflavin has been introduced as a new treatment for progressive keratoconus. The results of clinical studies are promising, but the efficacy of the treatment in halting the progression depends on the stability of the induced biomechanical effects. The effects of corneal CXL on corneal rigidity; collagen fiber diameter; and resistance to heat degradation, enzymatic digestion, and swelling due to hydration are reviewed in this paper. The collective results indicate that CXL using UVA and riboflavin enhances the biomechanical properties of the corneal tissue, which remain stable over time. Therefore, this treatment could become the future standard therapy for keratoconus or used to halt the progression of keratoconus and postpone the need for corneal transplantation. The increase in availability and popularity of the CXL technique accentuates the requirement for reliable and accurate techniques for measuring corneal biomechanical properties before and after treatment. PMID:23506922

  15. Donor Age and Corneal Endothelial Cell Loss 5 Years after Successful Corneal Transplantation: Specular Microscopy Ancillary Study Results

    PubMed Central

    2010-01-01

    Objective To determine whether endothelial cell loss 5 years after successful corneal transplantation is related to the age of the donor. Design Multicenter, prospective, double-masked clinical trial. Participants Three hundred forty-seven subjects participating in the Cornea Donor Study who had not experienced graft failure 5 years after corneal transplantation for a moderate-risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema). Testing Specular microscopic images of donor corneas obtained before surgery and postoperatively at 6 months, 12 months, and then annually through 5 years were submitted to a central reading center to measure endothelial cell density (ECD). Main Outcome Measure Endothelial cell density at 5 years. Results At 5 years, there was a substantial decrease in ECD from baseline for all donor ages. Subjects who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 69% in the study eye, resulting in a 5-year median ECD of 824 cells/mm2 (interquartile range, 613–1342), whereas subjects who received a cornea from a donor 66 to 75 years old experienced a cell loss of 75%, resulting in a median 5-year ECD of 654 cells/mm2 (interquartile range, 538–986) (P [adjusted for baseline ECD] = 0.04). Statistically, there was a weak negative association between ECD and donor age analyzed as a continuous variable (r [adjusted for baseline ECD] = −0.19; 95% confidence interval, −0.29 to −0.08). Conclusions Endothelial cell loss is substantial in the 5 years after corneal transplantation. There is a slight association between cell loss and donor age. This finding emphasizes the importance of longer-term follow-up of this cohort to determine if this relationship affects graft survival. PMID:18387408

  16. Error induced by the estimation of the corneal power and the effective lens position with a rotationally asymmetric refractive multifocal intraocular lens

    PubMed Central

    Piñero, David P.; Camps, Vicente J.; Ramón, María L.; Mateo, Verónica; Pérez-Cambrodí, Rafael J.

    2015-01-01

    AIM To evaluate the prediction error in intraocular lens (IOL) power calculation for a rotationally asymmetric refractive multifocal IOL and the impact on this error of the optimization of the keratometric estimation of the corneal power and the prediction of the effective lens position (ELP). METHODS Retrospective study including a total of 25 eyes of 13 patients (age, 50 to 83y) with previous cataract surgery with implantation of the Lentis Mplus LS-312 IOL (Oculentis GmbH, Germany). In all cases, an adjusted IOL power (PIOLadj) was calculated based on Gaussian optics using a variable keratometric index value (nkadj) for the estimation of the corneal power (Pkadj) and on a new value for ELP (ELPadj) obtained by multiple regression analysis. This PIOLadj was compared with the IOL power implanted (PIOLReal) and the value proposed by three conventional formulas (Haigis, Hoffer Q and Holladay I). RESULTS PIOLReal was not significantly different than PIOLadj and Holladay IOL power (P>0.05). In the Bland and Altman analysis, PIOLadj showed lower mean difference (-0.07 D) and limits of agreement (of 1.47 and -1.61 D) when compared to PIOLReal than the IOL power value obtained with the Holladay formula. Furthermore, ELPadj was significantly lower than ELP calculated with other conventional formulas (P<0.01) and was found to be dependent on axial length, anterior chamber depth and Pkadj. CONCLUSION Refractive outcomes after cataract surgery with implantation of the multifocal IOL Lentis Mplus LS-312 can be optimized by minimizing the keratometric error and by estimating ELP using a mathematical expression dependent on anatomical factors. PMID:26085998

  17. Effect of laser polarization and pulse energy on therapeutic, femtosecond laser-induced second harmonic generation in corneal tissue (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Calhoun, William R.; Ilev, Ilko K.

    2016-03-01

    Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (e.g. cataract surgery), and keratoplasty (cornea transplant), now employ therapeutic infrared femtosecond lasers (FSLs) for their extreme precision, low energy delivered into tissue and advanced ablation characteristics. Although the widely exploited applications of FSLs in medical therapeutics offer significant benefits, FSLs must generate very high intensities in order to achieve optical breakdown, the predominant tissue ablative mechanism, which can also stimulate nonlinear optical effects such as harmonic generation, an effect that generates coherent visible and UV light in the case of second- (SHG) and third-harmonic generation (THG), respectively. In order to improve the understanding of HG in corneal tissue, the effect of FSL polarization and pulse energy were investigated. FSL stimulated SHG intensity in corneal tissue was measured as the laser polarization was rotated 360 degrees. Further, the pulse energy at the SHG wavelength were measured for single FSL pulses as the pulse energy at the fundamental wavelength was varied through a range of clinically relevant values. The results of this study revealed SHG intensity oscillated with laser polarization, having a variation greater than 20%. This relationship seems to due to the intrinsic anisotropy of collagen fibril hyperpolarizability, not related to tissue birefringence. SHG pulse energy measurements showed an increase in SHG pulse energy with increasing FSL pulse energy, however conversion efficiency decreased. This may be related to the dynamic relationship between optical breakdown leading to tissue destruction and HG evolution.

  18. Biocompatibility and drug release behavior of chitosan/poly (vinyl alcohol) corneal shield in vivo

    PubMed Central

    Li, Guo-Xing; Gu, Xin; Song, Hui-Yang; Nan, Kai-Hui; Chen, Hao

    2015-01-01

    Backgound: Chitosan/polyvinyl alcohol corneal cap has good biocompatibility and drug slow release characteristics, which provided new treatment method for anterior segment disease. Our study was to evaluate biocompatibility of poly (vinyl alcohol)/chitosan corneal shield’s intraocular and investigate its feasibility to treat ocular surface disorders. Methods: Thirty-six white rabbits were randomly divided into four groups. Slit lamp observation were conducted at 1, 3, 7 and 10 days after operation. Corneal and conjunctiva tissue harvested from the experimental groups was observed by HE staining 10 days after operation. The aqueous humor was aspirated from the anterior chamber at each designated time point (1, 3, 7 and 10 days). The cornea and conjunctive were collected at 10 days. The concentration of each tissue was analyzed by ultra-performance liquid chromatography and microscope observation. Results: In all groups, mild hyperemia was observed 1 day after operation, and there was no obvious inflammatory reaction occurring on the seventh and tenth day. No corneal edema and inflammatory reaction of anterior chamber occurred till the tenth day. For histopathology, there was no obviously mild chronic and inflammatory reaction occurred, and no significant difference between the corneal shield with-in groups and with-out groups. The drug concentrations in corneal and conjunctival in group (A, B) were significantly lower than eye drops in the control group (C, D), and blank corneal cover in group C was significantly sham operation in group D. Conclusion: The results indicated that the proposed membrane combined with ophthalmic solution has substantial potential as ocular delivery system. PMID:26550213

  19. Substrates for Expansion of Corneal Endothelial Cells towards Bioengineering of Human Corneal Endothelium

    PubMed Central

    Navaratnam, Jesintha; Utheim, Tor P.; Rajasekhar, Vinagolu K.; Shahdadfar, Aboulghassem

    2015-01-01

    Corneal endothelium is a single layer of specialized cells that lines the posterior surface of cornea and maintains corneal hydration and corneal transparency essential for vision. Currently, transplantation is the only therapeutic option for diseases affecting the corneal endothelium. Transplantation of corneal endothelium, called endothelial keratoplasty, is widely used for corneal endothelial diseases. However, corneal transplantation is limited by global donor shortage. Therefore, there is a need to overcome the deficiency of sufficient donor corneal tissue. New approaches are being explored to engineer corneal tissues such that sufficient amount of corneal endothelium becomes available to offset the present shortage of functional cornea. Although human corneal endothelial cells have limited proliferative capacity in vivo, several laboratories have been successful in in vitro expansion of human corneal endothelial cells. Here we provide a comprehensive analysis of different substrates employed for in vitro cultivation of human corneal endothelial cells. Advances and emerging challenges with ex vivo cultured corneal endothelial layer for the ultimate goal of therapeutic replacement of dysfunctional corneal endothelium in humans with functional corneal endothelium are also presented. PMID:26378588

  20. [Distal post-traumatic edema--symptom of a sympathetic reflex dystrophy (Sudeck's disease)?].

    PubMed

    Blumberg, H; Griesser, H J; Hornyak, M

    1992-01-01

    The present paper describes various mechanisms, possibly being involved in the development of the posttraumatic, distally generalized edema. New ideas point to a special importance of the sympathetic vasoconstrictor system for this clinical phenomenon, since this system could induce an enhanced venoconstriction at the exit of the capillary bed, which would result in an edema producing diminished venous return. Since the distally generalized edema is an initially and very commonly occurring symptom of reflex sympathetic dystrophy (M. Sudeck), the observation of such an edema should lead one to look for further symptoms of this disorder, especially for the typical triad of autonomic (sympathetic), motor, and sensory disturbances. PMID:1372460

  1. [Hereditary angioneurotic edema in children].

    PubMed

    Farkas, H; Harmat, G; Füst, G; Varga, L; Visy, B

    2000-11-19

    Hereditary angioneurotic edema results from the deficiency of C1-esterase inhibitor. The clinical picture of this autosomal dominant disorder is characterized by recurrent attacks of edema formation in the subcutis and/or the submucosa. The clinical records of 21 children with established hereditary angioneurotic edema were reviewed. Follow-up care included laboratory check-ups and abdominal ultrasound. Clinical manifestations of the disease first occurred in 2.5 to 12 years of age. Mechanical trauma was the most common precipitating factor. Pedigree-analysis revealed 19 patients with afflicted relatives. Long-term prophylaxis was initiated with tranexamic acid and danazol in 10 cases; 2 children required short-term prophylaxis. Therapy improved serum complement parameters significantly and reduced the frequency and severity of clinical manifestations. Acute, life-threatening edematous attacks were treated by the administration of C1-inhibitor concentrate, which achieved the resolution of the edema within several hours. Abdominal ultrasonography performed during the attack invariably demonstrated transitory ascites that resolved spontaneously after treatment. Adequate prophylaxis and follow-up care can spare pediatric patients from edematous attacks. Undesirable adverse effects can be avoided and the patient's quality of life can be enhanced considerably by administering the lowest effective drug dose. PMID:11143287

  2. Traumatic corneal endothelial rings from homemade explosives.

    PubMed

    Ng, Soo Khai; Rudkin, Adam K; Galanopoulos, Anna

    2013-08-01

    Traumatic corneal endothelial rings are remarkably rare ocular findings that may result from blast injury. We present a unique case of bilateral traumatic corneal endothelial rings secondary to blast injury from homemade explosives. PMID:23474743

  3. CORNEAL ANGIOGENIC PRIVILEGE: ANGIOGENIC AND ANTIANGIOGENIC FACTORS IN CORNEAL AVASCULARITY, VASCULOGENESIS, AND WOUND HEALING (AN AMERICAN OPHTHALMOLOGICAL SOCIETY THESIS)

    PubMed Central

    Azar, Dimitri T.

    2006-01-01

    Purpose To determine the molecular basis of corneal avascularity during wound healing and determine the role of angiogenic and antiangiogenic factors in corneal vasculogenesis. Methods The expression of proangiogenic factors (vascular endothelial growth factor [VEGF]; basic fibroblast growth factor [bFGF]; matrix metalloproteinase-2 [MMP-2]; and membrane-type 1-MMP [MT1-MMP]) and antiangiogenic factors (pigment epithelium–derived factor [PEDF]; angiostatin; restin; and endostatin) was analyzed in avascular corneas and in models of corneal neovascularization (bFGF pellet implantation, intrastromal injection of MT1-MMP cDNA, and surgically induced partial limbal deficiency). Results Immunohistochemistry demonstrated the presence of antiangiogenic factors (PEDF, angiostatin, restin, and endostatin) and proangiogenic molecules (VEGF, bFGF, MMP-2, and MT1-MMP) in the cornea after wounding. Proangiogenic MMPs were upregulated in stromal fibroblasts in the vicinity of invading vessels following bFGF pellet implantation. Corneal neovascularization (NV) was also induced by intrastromal injection of MT1-MMP naked cDNA in conjunction with de-epithelialization. Partial limbal deficiency (HLD-) resulted in corneal NV in MMP-7 and MMP-3 knockout mice but not in wild type controls. Conclusions Corneal angiogenic privilege is an active process involving the production of antiangiogenic factors to counterbalance the proangiogenic factors (which are upregulated after wound healing even in the absence of new vessels). Our finding that the potent antiangiogenic factors, angiostatin and endostatin, are colocalized with several MMPs during wound healing suggests that MMPs may be involved in the elaboration of these antiangiogenic molecules by proteolytic processing of substrates within the cornea. PMID:17471348

  4. Anti-inflammatory and anti-hyperalgesic effect of all-trans retinoic acid in carrageenan-induced paw edema in Wistar rats: Involvement of peroxisome proliferator-activated receptor-β/δ receptors

    PubMed Central

    Gill, Navneet; Bijjem, Krishna Reddy V.; Sharma, Pyare L.

    2013-01-01

    Objective: In this study, we investigated the role of peroxisome proliferator-activated receptors (PPAR)-β/δ receptors in carrageenan-induced inflammation and in the anti-inflammatory effects of all-trans retinoic acid (ATRA). Materials and Methods: The λ-carrageenan (0.1 ml of 1% w/v) was injected into intra-plantar (i.pl.) region of the hind paw to produce acute inflammation. Paw volume was measured by using the mercury plethysmography. Further, mechanical and thermal hyperalgesia (TH) were assessed by using the dynamic plantar aesthesiometer and plantar test apparatus, respectively. In addition, markers of oxido-nitrosative stress were assessed spectrophotometrically in the hind paw tissue 5 h post-carrageenan. Results: An i.pl injection of carrageenan has produced a marked mechanical hyperalgesia (MH) and TH in ipsilateral paw, which was associated with significant elevated oxido-nitrosative stress. Treatment with ATRA (5 mg/kg/p.o/4 days) and GW0742, a selective PPAR-β/δ receptor agonist (0.1 mg/kg/i.p/4 days), significantly decreased the paw volume, mechanical and TH as compared to vehicle control. Administration of GSK0660, selective PPAR-β/δ receptor antagonist, at a dose of (0.3 mg/kg/i.p/4 days), did not produce a significant effect on carrageenan-induced paw edema, MH and TH. However, co-administration of GSK0660 (0.3 mg/kg/i.p/4 days) along with both ATRA (5 mg/kg/p.o/4 days) and GW0742 (0.1 mg/kg/i.p/4 days), significantly reverse the decreased paw edema, MH, and TH. These observed ameliorative effects on inflammatory pain symptoms are correlated with the extent of reduction of oxido-nitrosative stress. Conclusion: From above findings, it can be concluded that ATRA exerts anti-inflammatory and anti-hyperalgesic effect, possibly through activation of PPAR-β/δ and subsequent reduction of oxido-nitrosative stress. PMID:23833373

  5. Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction

    PubMed Central

    Okumura, Naoki; Sakamoto, Yuji; Fujii, Keita; Kitano, Junji; Nakano, Shinichiro; Tsujimoto, Yuki; Nakamura, Shin-ichiro; Ueno, Morio; Hagiya, Michio; Hamuro, Junji; Matsuyama, Akifumi; Suzuki, Shingo; Shiina, Takashi; Kinoshita, Shigeru; Koizumi, Noriko

    2016-01-01

    The corneal endothelium maintains corneal transparency; consequently, its dysfunction causes severe vision loss. Tissue engineering-based therapy, as an alternative to conventional donor corneal transplantation, is anticipated to provide a less invasive and more effective therapeutic modality. We conducted a preclinical study for cell-based therapy in a primate model and demonstrated regeneration of the corneal endothelium following injection of cultured monkey corneal endothelial cells (MCECs) or human CECs (HCECs), in combination with a Rho kinase (ROCK) inhibitor, Y-27632, into the anterior chamber. We also evaluated the safety and efficacy of Good Manufacturing Practice (GMP)-grade HCECs, similar to those planned for use as transplant material for human patients in a clinical trial, and we showed that the corneal endothelium was regenerated without adverse effect. We also showed that CEC engraftment is impaired by limited substrate adhesion, which is due to actomyosin contraction induced by dissociation-induced activation of ROCK/MLC signaling. Inclusion of a ROCK inhibitor improves efficiency of engraftment of CECs and enables cell-based therapy for treating corneal endothelial dysfunction as a clinically relevant therapy. PMID:27189516

  6. Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction.

    PubMed

    Okumura, Naoki; Sakamoto, Yuji; Fujii, Keita; Kitano, Junji; Nakano, Shinichiro; Tsujimoto, Yuki; Nakamura, Shin-Ichiro; Ueno, Morio; Hagiya, Michio; Hamuro, Junji; Matsuyama, Akifumi; Suzuki, Shingo; Shiina, Takashi; Kinoshita, Shigeru; Koizumi, Noriko

    2016-01-01

    The corneal endothelium maintains corneal transparency; consequently, its dysfunction causes severe vision loss. Tissue engineering-based therapy, as an alternative to conventional donor corneal transplantation, is anticipated to provide a less invasive and more effective therapeutic modality. We conducted a preclinical study for cell-based therapy in a primate model and demonstrated regeneration of the corneal endothelium following injection of cultured monkey corneal endothelial cells (MCECs) or human CECs (HCECs), in combination with a Rho kinase (ROCK) inhibitor, Y-27632, into the anterior chamber. We also evaluated the safety and efficacy of Good Manufacturing Practice (GMP)-grade HCECs, similar to those planned for use as transplant material for human patients in a clinical trial, and we showed that the corneal endothelium was regenerated without adverse effect. We also showed that CEC engraftment is impaired by limited substrate adhesion, which is due to actomyosin contraction induced by dissociation-induced activation of ROCK/MLC signaling. Inclusion of a ROCK inhibitor improves efficiency of engraftment of CECs and enables cell-based therapy for treating corneal endothelial dysfunction as a clinically relevant therapy. PMID:27189516

  7. Noncontact depth-resolved micro-scale corneal elastography

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Larin, Kirill V.

    2015-03-01

    Noninvasive high-resolution depth-resolved measurement of corneal biomechanics is of great clinical significance for improving the diagnosis and optimizing the treatment of various degenerated ocular diseases. Here, we report a micro-scale optical coherence elastography (OCE) method that enables noncontact assessment of the depthwise elasticity distribution in the cornea. The OCE system combines a focused air-puff device with phase-sensitive optical coherence tomography (OCT). Low-pressure short-duration air stream is used to load the cornea with the localized displacement at micron level. The phase-resolved OCT detection with nano-scale sensitivity probes the induced corneal deformation at various locations within a scanning line, providing the ultra-fast imaging of the corneal lamb wave propagation. With spectral analysis, the amplitude spectra and the phase spectra are available for the estimation of the frequency range of the lamb wave and the quantification of the wave propagation, respectively. Curved propagation paths following the top and bottom corneal boundaries are selected inside the cornea for measuring the phase velocity of the lamb wave at the major frequency components over the whole depths. Our pilot experiments on ex vivo rabbit eyes indicate the distinct stiffness of different layers in the cornea, including the epithelium, the anterior stroma, the posterior stroma, and the innermost region, which demonstrates the feasibility of this micro-scale OCE method for noncontact depth-resolved corneal elastography. Also, the quantification of the lamb wave dispersion in the cornea could lead to the measurement of the elastic modulus, suggesting the potential of this method for quantitative monitoring of the corneal biomechanics.

  8. WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis.

    PubMed

    Ouyang, Hong; Xue, Yuanchao; Lin, Ying; Zhang, Xiaohui; Xi, Lei; Patel, Sherrina; Cai, Huimin; Luo, Jing; Zhang, Meixia; Zhang, Ming; Yang, Yang; Li, Gen; Li, Hairi; Jiang, Wei; Yeh, Emily; Lin, Jonathan; Pei, Michelle; Zhu, Jin; Cao, Guiqun; Zhang, Liangfang; Yu, Benjamin; Chen, Shaochen; Fu, Xiang-Dong; Liu, Yizhi; Zhang, Kang

    2014-07-17

    The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs), and deficiency in LSCs or corneal epithelium--which turns cornea into a non-transparent, keratinized skin-like epithelium--causes corneal surface disease that leads to blindness in millions of people worldwide. How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases. PMID:25030175

  9. Gene Therapy in Corneal Transplantation

    PubMed Central

    Qazi, Yureeda; Hamrah, Pedram

    2014-01-01

    Corneal transplantation is the most commonly performed organ transplantation. Immune privilege of the cornea is widely recognized, partly because of the relatively favorable outcome of corneal grafts. The first-time recipient of corneal allografts in an avascular, low-risk setting can expect a 90% success rate without systemic immunosuppressive agents and histocompatibility matching. However, immunologic rejection remains the major cause of graft failure, particularly in patients with a high risk for rejection. Corticosteroids remain the first-line therapy for the prevention and treatment of immune rejection. However, current pharmacological measures are limited in their side-effect profiles, repeated application, lack of targeted response, and short duration of action. Experimental ocular gene therapy may thus present new horizons in immunomodulation. From efficient viral vectors to sustainable alternative splicing, we discuss the progress of gene therapy in promoting graft survival and postulate further avenues for gene-mediated prevention of allogeneic graft rejection. PMID:24138037

  10. Corneal neovascularization and biological therapy

    PubMed Central

    Voiculescu, OB; Voinea, LM; Alexandrescu, C

    2015-01-01

    Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions. Corneal neovascularization (NV) is a condition that can develop in response to inflammation, hypoxia, trauma, or limbal stem cell deficiency and it is a significant cause of blindness. New therapeutic options for diseases of the cornea and ocular surface are now being explored in experimental animals and clinical trials. Antibody based biologics are being tested for their ability to reduce blood and lymphatic vessel ingrowth into the cornea, and to reduce inflammation. Numerous studies have shown that biologics with specificity for VEGF A such as bevacizumab and ranibizumab (a recombinant antibody and an antibody fragment, respectively) or anti-tumor necrosis factor-α microantibody, are effective in the treatment of corneal neovascularization. PMID:26664467

  11. B7 Costimulation Molecules Encoded by Replication-Defective, vhs-Deficient HSV-1 Improve Vaccine-Induced Protection against Corneal Disease

    PubMed Central

    Schrimpf, Jane E.; Tu, Eleain M.; Wang, Hong; Wong, Yee M.; Morrison, Lynda A.

    2011-01-01

    Herpes simplex virus 1 (HSV-1) causes herpes stromal keratitis (HSK), a sight-threatening disease of the cornea for which no vaccine exists. A replication-defective, HSV-1 prototype vaccine bearing deletions in the genes encoding ICP8 and the virion host shutoff (vhs) protein reduces HSV-1 replication and disease in a mouse model of HSK. Here we demonstrate that combining deletion of ICP8 and vhs with virus-based expression of B7 costimulation molecules created a vaccine strain that enhanced T cell responses to HSV-1 compared with the ICP8−vhs− parental strain, and reduced the incidence of keratitis and acute infection of the nervous system after corneal challenge. Post-challenge T cell infiltration of the trigeminal ganglia and antigen-specific recall responses in local lymph nodes correlated with protection. Thus, B7 costimulation molecules expressed from the genome of a replication-defective, ICP8−vhs− virus enhance vaccine efficacy by further reducing HSK. PMID:21826207

  12. Augmented anti-angiogenesis activity of polysulfated heparin-endostatin and polyethylene glycol-endostatin in alkali burn-induced corneal ulcers in rabbits

    PubMed Central

    LI, ZHAO-NA; YUAN, ZHONG-FANG; MU, GUO-YING; HU, MING; CAO, LI-JUN; ZHANG, YA-LI; GE, MING-XU

    2015-01-01

    Endostatin (ES) is an endogenous angiogenesis inhibitor that has the ability to inhibit tumor growth and metastasis. However, its clinical application is limited by a number of disadvantages, such as poor stability, short half-life and the requirement of high doses to maintain its efficacy. The chemical modification on ES may offer a solution to these disadvantages. The aim of the present study was to evaluate the effects of ES, polysulfated heparin-endostatin (PSH-ES) and polyethylene glycol-endostatin (PEG-ES) on the endothelial cell proliferation and angiogenesis associated with corneal neovascularization (CNV) and to determine their mechanisms of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro, and rabbits were used to evaluate the effects of ES and its derivatives on CNV in vivo. In the evaluation of CNV, the expression of vascular endothelial growth factor in the cornea was measured via immunohistochemistry and microvessels were counted. ES and its derivatives significantly inhibited endothelial cell proliferation in vitro (P<0.05) and suppressed CNV in vivo. Among the compounds examined, ES most effectively inhibited endothelial cell proliferation in vitro (P<0.05); however, PSH-ES and PEG-ES most effectively inhibited CNV in vivo (P<0.05). These results indicate that PSH-ES and PEG-ES are candidate anti-angiogenesis drugs. PMID:26622410

  13. Correlations between corneal and total wavefront aberrations

    NASA Astrophysics Data System (ADS)

    Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo

    2002-06-01

    Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p < 0.05) between the corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.

  14. Inhibitory effect of trichostatin on allograft rejection of corneal transplantation in rats

    PubMed Central

    Maimaitiming, Reziwan; Yang, Xin; Wupuer, Kelala; Ye, Nan; Pan, Zhiqiang

    2015-01-01

    Background: Using a rat penetrating keratoplasty model, this study aims to explore the inhibitory effect of hachimycin on corneal graft rejection, to provide new basis for its clinical application. Materials and methods: Female adult Sprague-Dawley (SD) rats weighing between 220-250 g were used as acceptors and male or female Wistar rats weighing between 220-250 g were used as donors. The rats with a successful keratoplasty were randomly divided into 3 groups with 10 rats in each group. Group A: penetrating keratoplasty group; Group B: penetrating keratoplasty followed by the application of control eye drops containing eye drops matrix dissolved in 20 g/L DMSO and 900 mL/L artificial tear; Group C: penetrating keratoplasty followed by the application of 0.5 g/L hachimycin eye drops. Hachimycin was dissolved in vitamin E to obtain an eye solution with a pH value of 6~7, and stored at 4°C. The local application of hachimycin eye drops started 5 days after the keratoplasty surgery, 5 times per day until the onset of rejection response. At 4 days after the keratoplasty surgery, slit-lamp microscope was used to observe the transplanted cornea once every two days, and a rejection index (RI) of 0-12 was obtained according to the three graft components represented by corneal transparency, edema, and corneal neovascularization. Results: Penetrating keratoplasty was successfully performed on all the 3 groups of rats. Five days after the keratoplasty, both the transparency and the implant edema showed a score of 1-2 degrees in group A and B. Two weeks later, both these two grafts components increased to a score of 2-3 degrees in group A and B, with an active neovascularization. The group C also showed a transparency and implant edema of 1-2 degrees five days after the keratoplasty surgery. However, a transparent implant without edema was observed in group C two weeks after the keratoplasty surgery. In addition, the newly formed blood vessels disappeared and the retina

  15. Precision Measurement Of Corneal Topography

    NASA Astrophysics Data System (ADS)

    Yoder, Paul R.; Macri, Timothy F.; Telfair, William B.; Bennett, Peter S.; Martin, Clifford A.; Warner, John W.

    1989-05-01

    We describe a new electro-optical device being developed to provide precise measurements of the three-dimensional topography of the human cornea. This device, called a digital keratoscope, is intended primarily for use in preparing for and determining the effect of corneal surgery procedures such as laser refractive keratectomy, radial keratotomy or corneal transplant on the refractive power of the cornea. It also may serve as an aid in prescribing contact lenses. The basic design features of the hardware and of the associated computer software are discussed, the means for alignment and calibration are described and typical results are given.

  16. [The cicatrization of corneal wounds].

    PubMed

    Spineanu, L

    1995-01-01

    The tissular mending of the corneal surface is the result of a complex series of various physiopathological responses. This structural regeneration involves a primary reconstruction and a secondary one. The primary reconstruction of the barrier function provides the restoring of the normal equilibrium of osmotic, thermal and metabolic exchanges. The primary cicatricial response's goal is the fast coating of the corneal plague and mainly involves an inflammatory response. The major stages of this initial sequence are: the migration of the polynuclear neutrophils into the plaque, the establishment of a fibrinous cork, the collapsing and then the migration of the epithelial cork, and the contraction of the keratocyte mesh. PMID:7577908

  17. Pulmonary edema following scorpion envenomation: mechanisms, clinical manifestations, diagnosis and treatment.

    PubMed

    Bahloul, Mabrouk; Chaari, Anis; Dammak, Hassen; Samet, Mohamed; Chtara, Kamilia; Chelly, Hedi; Ben Hamida, Chokri; Kallel, Hatem; Bouaziz, Mounir

    2013-01-10

    Scorpion envenomation is common in tropical and subtropical regions. Cardio-respiratory manifestations, mainly cardiogenic shock and pulmonary edema, are the leading causes of death after scorpion envenomation. The mechanism of pulmonary edema remains unclear and contradictory conclusions were published. However, most publications confirm that pulmonary edema has been attributed to acute left ventricular failure. Cardiac failure can result from massive release of catecholamines, myocardial damage induced by the venom or myocardial ischemia. Factors usually associated with the diagnosis of pulmonary edema were young age, tachypnea, agitation, sweating, or the presence of high plasma protein concentrations. Treatment of scorpion envenomation has two components: antivenom administration and supportive care. The latter mainly targets hemodynamic impairment and cardiogenic pulmonary edema. In Latin America, and India, the use of Prazosin is recommended for treatment of pulmonary edema because pulmonary edema is associated with arterial hypertension. However, in North Africa, scorpion leads to cardiac failure with systolic dysfunction with normal vascular resistance and dobutamine was recommended. Dobutamine infusion should be used as soon as we have enough evidence suggesting the presence of pulmonary edema, since it has been demonstrated that scorpion envenomation can result in pulmonary edema secondary to acute left ventricular failure. In severe cases, mechanical ventilation can be required. PMID:22075406

  18. Ischemia and reperfusion of the lung tissues induced increase of lung permeability and lung edema is attenuated by dimethylthiourea (PP69).

    PubMed

    Chen, K H; Chao, D; Liu, C F; Chen, C F; Wang, D

    2010-04-01

    This study sought to determine whether oxygen radical scavengers of dimethylthiourea (DMTU), superoxide dismutase (SOD), or catalase (CAT) pretreatment attenuated ischemia-reperfusion (I/R)-induced lung injury. After isolation from a Sprague-Dawley rat, the lungs were perfused through the pulmonary artery cannula with rat whole blood diluted 1:1 with a physiological salt solution. An acute lung injury was induced by 10 minutes of hypoxia with 5% CO2-95% N2 followed by 65 minutes of ischemia and then 65 minutes of reperfusion. I/R significantly increased microvascular permeability as measured by the capillary filtration coefficient (Kfc), lung weight-to-body weight ratio (LW/BW), and protein concentration in bronchoalveolar lavage fluid (PCBAL). DMTU pretreatment significantly attenuated the acute lung injury. The capillary filtration coefficient (P<.01), LW/BW (P<.01) and PCBAL (P<.05) were significantly lower among the DMTU-treated rats than hosts pretreated with SOD or CAT. The possible mechanisms of the protective effect of DMTU in I/R-induced lung injury may relate to the permeability of the agent allowing it to scavenge intracellular hydroxyl radicals. However, whether superoxide dismutase or catalase antioxidants showed protective effects possibly due to their impermeability of the cell membrane not allowing scavenging of intracellular oxygen radicals. PMID:20430163

  19. History of corneal transplantation in Australia.

    PubMed

    Coster, Douglas J

    2015-04-01

    Corneal transplantation is a triumph of modern ophthalmology. The possibility of corneal transplantation was first raised in 1797 but a century passed before Zirm achieved the first successful penetrating graft in 1905. Gibson reported the first corneal graft in Australia from Brisbane in 1940 and English established the first eye bank there a few years later. Corneal transplantation evolved steadily over the twentieth century. In the second half of the century, developments in microsurgery, including surgical materials such as monofilament nylon and strong topical steroid drops, accounted for improvements in outcomes. In 2013, approximately 1500 corneal transplants were done in Australia. Eye banking has evolved to cope with the rising demands for donor corneas. Australian corneal surgeons collaborated to establish and support the Australian Corneal Graft Registry in 1985. It follows the outcomes of their surgery and has become an important international resource for surgeons seeking further improvement with the procedure. PMID:25112897

  20. Corneal Regeneration After Photorefractive Keratectomy: A Review☆

    PubMed Central

    Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger

    2014-01-01

    Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain. PMID:25444646

  1. Corneal Regeneration After Photorefractive Keratectomy: A Review.

    PubMed

    Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger

    2015-01-01

    Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain. PMID:25444646

  2. Edema formation in spinal nerve roots induced by experimental, graded compression. An experimental study on the pig cauda equina with special reference to differences in effects between rapid and slow onset of compression.

    PubMed

    Olmarker, K; Rydevik, B; Holm, S

    1989-06-01

    Edema formation in spinal nerve roots of the pig cauda equina was studied following experimental compression at various pressure levels, durations, and rates of onset, using a fluorescence microscopic technique. The time-pressure thresholds for the occurrence of edema in the nerve roots were: following rapid onset of compression (0.05-0.1 seconds), 2 minutes at both 50 mm Hg and 200 mm Hg, and following slow onset of compression (the pressure was slowly increased during 15-20 seconds), 2 hours at 50 mm Hg and 2 minutes at 200 mm Hg. Generally, the edema formation was more pronounced after rapid than after slow onset of compression. The data in this study also indicate that intraneural edema might be more easily formed in nerve roots than in peripheral nerves after compression injury. PMID:2546258

  3. Tat-CBR1 inhibits inflammatory responses through the suppressions of NF-κB and MAPK activation in macrophages and TPA-induced ear edema in mice

    SciTech Connect

    Kim, Young Nam; Kim, Dae Won; Jo, Hyo Sang; Shin, Min Jea; Ahn, Eun Hee; Ryu, Eun Ji; Yong, Ji In; Cha, Hyun Ju; Kim, Sang Jin; Yeo, Hyeon Ji; Youn, Jong Kyu; Hwang, Jae Hyeok; Jeong, Ji-Heon; Kim, Duk-Soo; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-07-15

    Human carbonyl reductase 1 (CBR1) plays a crucial role in cell survival and protects against oxidative stress response. However, its anti-inflammatory effects are not yet clearly understood. In this study, we examined whether CBR1 protects against inflammatory responses in macrophages and mice using a Tat-CBR1 protein which is able to penetrate into cells. The results revealed that purified Tat-CBR1 protein efficiently transduced into Raw 264.7 cells and inhibited lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2), nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) expression levels. In addition, Tat-CBR1 protein leads to decreased pro-inflammatory cytokine expression through suppression of nuclear transcription factor-kappaB (NF-κB) and mitogen activated protein kinase (MAPK) activation. Furthermore, Tat-CBR1 protein inhibited inflammatory responses in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation when applied topically. These findings indicate that Tat-CBR1 protein has anti-inflammatory properties in vitro and in vivo through inhibition of NF-κB and MAPK activation, suggesting that Tat-CBR1 protein may have potential as a therapeutic agent against inflammatory diseases. - Highlights: • Transduced Tat-CBR1 reduces LPS-induced inflammatory mediators and cytokines. • Tat-CBR1 inhibits MAPK and NF-κB activation. • Tat-CBR1 ameliorates inflammation response in vitro and in vivo. • Tat-CBR1 may be useful as potential therapeutic agent for inflammation.

  4. Co-regulation of Dectin-1 and TLR2 in inflammatory response of human corneal epithelial cells induced by Aspergillus fumigates

    PubMed Central

    Zhao, Gui-Qiu; Qiu, Xue-Yan; Lin, Jing; Li, Qing; Hu, Li-Ting; Wang, Qian; Li, Hui

    2016-01-01

    AIM To investigate the co-regulation of dendritic cell-associated C-type lectin-1 (Dectin-1), Toll-like receptor 2 (TLR2), and relative chemotactic factors in the Telomease-immortalized human corneal epithelial (THCE) cells after exposure to Aspergillus fumigatus (Af) hyphae. METHODS The normal THCE cells were investigated as control. After cultured in vitro with Af hyphae, with or without laminarin and anti-TLR2 antibody for 4, 8, 16 and 24h, THCE cells were harvested. The expression of Dectin-1, TLR2, CXCL1 and CXCL8 mRNA were measured by real-time quantitative polymerase chain reaction at the stimulation of 4, 8 and 16h separately. The protein expression of Dectin-1 and TLR2 were analyzed at 8, 16, and 24h by Western blot. RESULTS The mRNA expression of CXCL1 and CXCL8 increased in THCE cells after stimulated by Af hyphae. The stimulatory effects on these inflammatory chemokines were shown in a dose-dependent manner and reached the peak at 8h. Af hyphae significantly stimulated the production of Dectin-1 and TLR2 in THCE cells at both mRNA and protein levels. The protein of Dectin-1 and TLR2 gradually increased till 16h. While pretreated with laminarin (a Dectin-1 inhibitor), the expression of TLR2, CXCL1 and CXCL8 all decreased dramatically at the peak point. Interestingly, when pretreated with TLR2 neutralizing antibody, the expression of Dectin-1, CXCL1 and CXCL8 also decreased dramatically at the peak point. CONCLUSION These findings suggest that Dectin-1 and TLR2 co-regulated with each other after treated with inactive Af hyphae in the THCE cells, and they contribute together to the inflammatory responses by induction of chemokines CXCL1 and CXCL8. PMID:26949633

  5. Discovery of molecular markers to discriminate corneal endothelial cells in the human body.

    PubMed

    Yoshihara, Masahito; Ohmiya, Hiroko; Hara, Susumu; Kawasaki, Satoshi; Hayashizaki, Yoshihide; Itoh, Masayoshi; Kawaji, Hideya; Tsujikawa, Motokazu; Nishida, Kohji

    2015-01-01

    The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant number of CECs results in corneal edema called bullous keratopathy which can lead to severe visual loss. Corneal transplantation is the most effective method to treat corneal endothelial dysfunction, where it suffers from donor shortage. Therefore, regeneration of CECs from other cell types attracts increasing interests, and specific markers of CECs are crucial to identify actual CECs. However, the currently used markers are far from satisfactory because of their non-specific expression in other cell types. Here, we explored molecular markers to discriminate CECs from other cell types in the human body by integrating the published RNA-seq data of CECs and the FANTOM5 atlas representing diverse range of cell types based on expression patterns. We identified five genes, CLRN1, MRGPRX3, HTR1D, GRIP1 and ZP4 as novel markers of CECs, and the specificities of these genes were successfully confirmed by independent experiments at both the RNA and protein levels. Notably none of them have been documented in the context of CEC function. These markers could be useful for the purification of actual CECs, and also available for the evaluation of the products derived from other cell types. Our results demonstrate an effective approach to identify molecular markers for CECs and open the door for the regeneration of CECs in vitro. PMID:25807145

  6. Discovery of Molecular Markers to Discriminate Corneal Endothelial Cells in the Human Body

    PubMed Central

    Yoshihara, Masahito; Ohmiya, Hiroko; Hara, Susumu; Kawasaki, Satoshi; Hayashizaki, Yoshihide; Itoh, Masayoshi; Kawaji, Hideya; Tsujikawa, Motokazu; Nishida, Kohji

    2015-01-01

    The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant number of CECs results in corneal edema called bullous keratopathy which can lead to severe visual loss. Corneal transplantation is the most effective method to treat corneal endothelial dysfunction, where it suffers from donor shortage. Therefore, regeneration of CECs from other cell types attracts increasing interests, and specific markers of CECs are crucial to identify actual CECs. However, the currently used markers are far from satisfactory because of their non-specific expression in other cell types. Here, we explored molecular markers to discriminate CECs from other cell types in the human body by integrating the published RNA-seq data of CECs and the FANTOM5 atlas representing diverse range of cell types based on expression patterns. We identified five genes, CLRN1, MRGPRX3, HTR1D, GRIP1 and ZP4 as novel markers of CECs, and the specificities of these genes were successfully confirmed by independent experiments at both the RNA and protein levels. Notably none of them have been documented in the context of CEC function. These markers could be useful for the purification of actual CECs, and also available for the evaluation of the products derived from other cell types. Our results demonstrate an effective approach to identify molecular markers for CECs and open the door for the regeneration of CECs in vitro. PMID:25807145

  7. Immunological aspects of corneal transplant.

    PubMed

    Kumar, Vijay; Kumar, Asha

    2014-01-01

    Corneal transplant is the most common solid tissue transplant in humans. Advances in microsurgical techniques, eye banking and the use of corticosteroids have improved the success of corneal transplants. Over 65,000 corneal transplants are being performed worldwide annually. Most of these transplants are performed in developed countries. Cornea is considered an immune privileged site. Despite this, immune mediated graft rejection is the most single cause of cornea graft failure and is one of the major postoperative complications. Incidences from as low as 2% to as high as 50% have been reported depending upon the degree of vascularization. Rejection involves donor tissue recognition and various factors may influence this rejection. Major factors include the antigenic load of the donor tissue; other factors include death to enucleation time, methods and temperature of preserving the tissue. Host factors that may impact the graft include ocular surface diseases such as dry eye, chemical burns and autoimmune diseases such as mucous membrane pemphigoid. Following infection, surgery or trauma, cells of the innate immune system invade the cornea as a result of up-regulation of cytokines, cellular adhesion molecules and growth and angiogenic factors. These factors results in neoangiogenesis and lymphoangiogenesis, leading to immune activation and graft rejection. The various immunological mechanisms that may play a role in the corneal transplant are discussed. PMID:25296240

  8. Fate Mapping Mammalian Corneal Epithelia.

    PubMed

    Richardson, Alexander; Wakefield, Denis; Di Girolamo, Nick

    2016-04-01

    The anterior aspect of the cornea consists of a stratified squamous epithelium, thought to be maintained by a rare population of stem cells (SCs) that reside in the limbal transition zone. Although migration of cells that replenish the corneal epithelium has been studied for over a century, the process is still poorly understood and not well characterized. Numerous techniques have been employed to examine corneal epithelial dynamics, including visualization by light microscopy, the incorporation of vital dyes and DNA labels, and transplantation of genetically marked cells that have acted as cell and lineage beacons. Modern-day lineage tracing utilizes molecular methods to determine the fate of a specific cell and its progeny over time. Classically employed in developmental biology, lineage tracing has been used more recently to track the progeny of adult SCs in a number of organs to pin-point their location and understand their movement and influence on tissue regeneration. This review highlights key discoveries that have led researchers to develop cutting-edge genetic tools to effectively and more accurately monitor turnover and displacement of cells within the mammalian corneal epithelium. Collating information on the basic biology of SCs will have clinical ramifications in furthering our knowledge of the processes that govern their role in homeostasis, wound-healing, transplantation, and how we can improve current unsatisfactory SC-based therapies for patients suffering blinding corneal disease. PMID:26774909

  9. [Current treatments for corneal neovascularization].

    PubMed

    Benayoun, Y; Petellat, F; Leclerc, O; Dost, L; Dallaudière, B; Reddy, C; Robert, P-Y; Salomon, J-L

    2015-12-01

    The extension of blood vessels into the normally avascular stroma defines corneal neovascularization. Though this phenomenon, pathophysiological and clinical features are well characterized, therapeutic modalities have been hindered by a lack of safe, efficacious and non-controversial treatments. In this literature review, we focus on available therapeutic options in light of recent evidence provided by animal and clinical studies. First, this review will focus on pharmacological treatments that target angiogenesis. The low cost and market availability of bevacizumab make it the first anti-angiogenic therapy choice, and it has demonstrable efficacy in reducing corneal neovascularization when administered topically or subconjunctivally. However, novel anti-angiogenic molecules targeting the intracellular pathways of angiogenesis (siRNA, antisense oligonucleotides) provide a promising alternative. Laser therapy (direct photocoagulation or photo-dynamic therapy) and fine needle diathermy also find a place in the treatment of stabilized corneal neovascularization alone or in association with anti-angiogenic therapy. Additionally, ocular surface reconstruction using amniotic membrane graft or limbal stem cell transplantation is essential when corneal neovascularization is secondary to primary or acquired limbal deficiency. PMID:26522890

  10. Antagonizing c-Cbl Enhances EGFR-Dependent Corneal Epithelial Homeostasis

    PubMed Central

    Rush, Jamie S.; Boeving, Michael A.; Berry, William L.; Ceresa, Brian P.

    2014-01-01

    Purpose. In many cell types, the E3 ubiquitin ligase, c-Cbl, induces ligand-dependent ubiquitylation of the epidermal growth factor receptor (EGFR) and targets the receptor for lysosomal degradation. The goal of this study was to determine whether c-Cbl is a negative regulator of EGFR in the corneal epithelium and if it can be inhibited to promote corneal epithelial homeostasis. Methods. Expression and activity of c-Cbl were blocked in immortalized human corneal epithelial cells (hTCEpi) using RNAi and pharmacological agents ([4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo-d-3,4-pyrimidine] or PP1). Following c-Cbl inhibition, cells were assessed for ligand-dependent receptor ubiquitylation, receptor phosphorylation, and in vitro wound healing. Subsequent experiments used PP1 in hTCEpi cells and monitored in vivo murine corneal epithelial wound healing. Results. Knockdown and inhibition of c-Cbl decreased ligand-dependent ubiquitylation of the EGFR and prolonged receptor activity as measured by tyrosine phosphorylation. Further, these treatments also increased the extent of ligand-dependent corneal epithelial wound healing in vitro and in vivo. Conclusion. Manipulating the duration of EGFR activity can enhance the rate of restoration of the corneal epithelial layer. Based on our findings, c-Cbl is a new therapeutic target to enhance EGFR-mediated corneal epithelial homeostasis that bypasses the limitations of previous approaches. PMID:24985478

  11. Corneal Stroma Microfibrils

    PubMed Central

    Hanlon, Samuel D.; Behzad, Ali R.; Sakai, Lynn Y.; Burns, Alan R.

    2015-01-01

    Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-β. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (∼10nm diameter). Immunogold evidence clearly

  12. Effects of topical 10% ascorbate solution on established corneal ulcers after severe alkali burns.

    PubMed

    Pfister, R R; Paterson, C A; Hayes, S A

    1982-03-01

    When established corneal ulcers induced by alkali burning were treated with 10% ascorbate drops, no perforation occurred, in contrast to a 25% incidence in the control group. If perforations and descemetoceles were grouped together, these difference became insignificant (i.e., 14.2% ascorbate-treated vs. 25% control). Prolongation of descemetocele presence without perforation in the ascorbate-treated group indicated some therapeutic effect. We conclude that topical ascorbate does not substantially alter the outcome of established corneal ulcers. PMID:7061209

  13. Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization

    PubMed Central

    Kim, Yoo C.; Grossniklaus, Hans E.; Edelhauser, Henry F.; Prausnitz, Mark R.

    2014-01-01

    Purpose. This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization. Methods. Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results. Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions. This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods. PMID:25212779

  14. Benzalkonium Chloride Suppresses Rabbit Corneal Endothelium Intercellular Gap Junction Communication

    PubMed Central

    Zhang, Zhenhao; Huang, Yue; Xie, Hui; Pan, Juxin; Liu, Fanfei; Li, Xuezhi; Chen, Wensheng; Hu, Jiaoyue; Liu, Zuguo

    2014-01-01

    Purpose Gap junction intercellular communication (GJIC) plays a critical role in the maintenance of corneal endothelium homeostasis. We determined if benzalkonium chloride (BAK) alters GJIC activity in the rabbit corneal endothelium since it is commonly used as a drug preservative in ocular eyedrop preparations even though it can have cytotoxic effects. Methods Thirty-six adult New Zealand albino rabbits were randomly divided into three groups. BAK at 0.01%, 0.05%, and 0.1% was applied twice daily to one eye of each of the rabbits in one of the three groups for seven days. The contralateral untreated eyes were used as controls. Corneal endothelial morphological features were observed by in vivo confocal microscopy (IVCM). Immunofluorescent staining resolved changes in gap junction integrity and localization. Western blot analysis and RT-PCR evaluated changes in levels of connexin43 (Cx43) and tight junction zonula occludens-1 (ZO-1) gene and protein expression, respectively. Cx43 and ZO-1 physical interaction was detected by immunoprecipitation (IP). Primary rabbit corneal endothelial cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing BAK for 24 hours. The scrape-loading dye transfer technique (SLDT) was used to assess GJIC activity. Results Topical administration of BAK (0.05%, 0.1%) dose dependently disrupted corneal endothelial cell morphology, altered Cx43 and ZO-1 distribution and reduced Cx43 expression. BAK also markedly induced increases in Cx43 phosphorylation status concomitant with decreases in the Cx43-ZO-1 protein-protein interaction. These changes were associated with marked declines in GJIC activity. Conclusions The dose dependent declines in rabbit corneal endothelial GJIC activity induced by BAK are associated with less Cx43-ZO-1 interaction possibly arising from increases in Cx43 phosphorylation and declines in its protein expression. These novel changes provide additional evidence that BAK containing eyedrop preparations

  15. Draining the edema: a new role for aquaretics?

    PubMed

    Bockenhauer, Detlef

    2014-05-01

    Investigations into edema formation in nephrotic syndrome have mostly focused on the primary role of sodium. While there is controversy about whether sodium retention is an inherent aspect of nephrotic syndrome (overfill hypothesis) or a secondary consequence (underfill hypothesis), the critical role of sodium in driving fluid retention is generally accepted. Consequently, treatment of edema is based on enhancing renal sodium excretion, using saluretics to block tubular reabsorption of sodium. However, there is also evidence of renal water retention: urine in nephrotic patients is typically highly concentrated (unless urinary concentrating ability is impaired by loop diuretics), and vasopressin levels are commonly elevated. Consequently, aquaretics, i.e., drugs that inhibit renal water reabsorption, may constitute effective treatments for nephrotic edema. In fact, these drugs are already approved for the treatment of non-nephrotic edematous states, such as those encountered in congestive heart or liver failure. In this edition of Pediatric Nephrology, two case reports raise the possibility that aquaretics may also be helpful in the treatment of nephrotic edema. These case reports provide no solid evidence for such treatment, and there clearly are serious concerns about inducing critical hypovolemia with potentially catastrophically consequences, such as thrombosis and shock. Yet these concerns similarly apply to saluretics, which clinicians routinely use in the treatment of edema. In addition, the described powerful effect of aquaretics with respect to the resolution of edema, as well as our understanding of the underlying physiology, argue for a more systematic, yet careful assessment of these drugs in the treatment of nephrotic syndrome. PMID:24482024

  16. Turning the tide of corneal blindness.

    PubMed

    Oliva, Matthew S; Schottman, Tim; Gulati, Manoj

    2012-01-01

    Corneal diseases represent the second leading cause of blindness in most developing world countries. Worldwide, major investments in public health infrastructure and primary eye care services have built a strong foundation for preventing future corneal blindness. However, there are an estimated 4.9 million bilaterally corneal blind persons worldwide who could potentially have their sight restored through corneal transplantation. Traditionally, barriers to increased corneal transplantation have been daunting, with limited tissue availability and lack of trained corneal surgeons making widespread keratoplasty services cost prohibitive and logistically unfeasible. The ascendancy of cataract surgical rates and more robust eye care infrastructure of several Asian and African countries now provide a solid base from which to dramatically expand corneal transplantation rates. India emerges as a clear global priority as it has the world's largest corneal blind population and strong infrastructural readiness to rapidly scale its keratoplasty numbers. Technological modernization of the eye bank infrastructure must follow suit. Two key factors are the development of professional eye bank managers and the establishment of Hospital Cornea Recovery Programs. Recent adaptation of these modern eye banking models in India have led to corresponding high growth rates in the procurement of transplantable tissues, improved utilization rates, operating efficiency realization, and increased financial sustainability. The widespread adaptation of lamellar keratoplasty techniques also holds promise to improve corneal transplant success rates. The global ophthalmic community is now poised to scale up widespread access to corneal transplantation to meet the needs of the millions who are currently blind. PMID:22944753

  17. Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model.

    PubMed

    Énzsöly, Anna; Markó, Katalin; Tábi, Tamás; Szökő, Éva; Zelkó, Romána; Tóth, Miklós; Petrash, J Mark; Mátyus, Péter; Németh, János

    2013-06-01

    The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p < 0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7-14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/SSAO activity in this model does not prevent the development of corneal neovascularization. PMID:23397320

  18. Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model

    PubMed Central

    Markó, Katalin; Tábi, Tamás; Szökő, Éva; Zelkó, Romána; Tóth, Miklós; Petrash, J. Mark; Mátyus, Péter; Németh, János

    2014-01-01

    The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/ semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p <0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7–14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/ SSAO activity in this model does not prevent the development of corneal neovascularization. PMID:23397320

  19. Hyaluronate Acid-Dependent Protection and Enhanced Corneal Wound Healing against Oxidative Damage in Corneal Epithelial Cells

    PubMed Central

    Zhong, Jing; Deng, Yuqing; Tian, Bishan; Wang, Bowen; Sun, Yifang; Huang, Haixiang; Chen, Ling; Ling, Shiqi; Yuan, Jin

    2016-01-01

    Purpose. To evaluate the effects and mechanism of exogenous hyaluronate (HA) in promoting corneal wound healing. Methods. Human corneal epithelial cells (HCECs) were incubated with different concentrations of HA to evaluate their efficiency in promoting cell migration and their modulation of repair factors. After inducing hyperosmolar conditions, the cell morphologies, cell apoptosis, and expression levels of TNF-α and MMP-9 were detected to assess the protective role of HA. Corneal epithelium-injured rat models were established to test the therapeutic effects of 0.3% HA. Then, the wound healing rates, the RNA expression levels of inflammatory cytokines, and repair factors were examined. Results. HCECs in the 0.03% and 0.3% HA groups showed fewer morphological alterations and lower rates of cell apoptosis following preincubation with HA under hyperosmolar conditions, as well as the expression levels of MMP-9 and TNF-α. In the rat model, the areas of fluorescein staining in the corneas of 0.3% HA group were significantly smaller than the control group. The expression levels of IL-1β and MMP-9 were decreased, while CD44 and FN were increased in the 0.3% HA group. Conclusion. HA enhanced corneal epithelial cell wound healing by promoting cell migration, upregulating repair responses, and suppressing inflammatory responses. PMID:27190638

  20. Hypoxia affects in vitro proliferation and differentiation of mouse corneal epithelial progenitor cell.

    PubMed

    Dong, Nuo; Qin, Wenjuan; Xue, Yuhua; Li, Cheng; Liu, Zuguo

    2013-08-01

    This study was to investigate the proliferation and differentiation of mouse corneal epithelial progenitor cell in hypoxic airlift culture. Mouse corneal epithelial progenitor cell line progenitor cells were cultured under airlift with normoxic and hypoxic conditions for various durations up to 2 wk. Under normoxic conditions when exposed to air, the hyperproliferation and abnormal epidermal-like differentiation of mouse corneal epithelium was induced, whereas when exposed to air under hypoxic conditions, although we observed augmented proliferation, the abnormal differentiation was inhibited. The mechanism by which hypoxia prevents abnormal differentiation may involve downregulation of Wnt signaling pathways, which were inhibited in cells cultured with hypoxic airlift technique. In conclusion, hypoxia can prevent abnormal differentiation while enhancing the proliferation of corneal epithelial cells by blocking Wnt/β-catenin signaling pathway. PMID:23739874

  1. Regenerative Cell Therapy for Corneal Endothelium.

    PubMed

    Bartakova, Alena; Kunzevitzky, Noelia J; Goldberg, Jeffrey L

    2014-09-01

    Endothelial cell dysfunction as in Fuchs dystrophy or pseudophakic bullous keratopathy, and the limited regenerative capacity of human corneal endothelial cells (HCECs), drive the need for corneal transplant. In response to limited donor corneal availability, significant effort has been directed towards cell therapy as an alternative to surgery. Stimulation of endogenous progenitors, or transplant of stem cell-derived HCECs or in vitro-expanded, donor-derived HCECs could replace traditional surgery with regenerative therapy. Ex vivo expansion of HCECs is technically challenging, and the basis for molecular identification of functional HCECs is not established. Delivery of cells to the inner layer of the human cornea is another challenge: different techniques, from simple injection to artificial corneal scaffolds, are being investigated. Despite remaining questions, corneal endothelial cell therapies, translated to the clinic, represent the future for the treatment of corneal endotheliopathies. PMID:25328857

  2. [Recent studies on corneal epithelial barrier function].

    PubMed

    Liu, F F; Li, W; Liu, Z G; Chen, W S

    2016-08-01

    Corneal epithelium, the outermost layer of eyeball, is the main route for foreign materials to enter the eye. Under physiological conditions, the corneal epithelial superficial cells form a functionally selective permeability barrier. Integral corneal epithelial barrier function not only ensures the enrolling of nutrients which is required for regular metabolism, but also prevents foreign bodies, or disease-causing microorganism invasion. Recently, a large number of clinical and experimental studies have shown that abnormal corneal epithelial barrier function is the pathological basis for many ocular diseases. In addition, some study found that corneal epithelial barrier constitutes a variety of proteins involved in cell proliferation, differentiation, apoptosis, and a series of physiological and pathological processes. This paper reviewed recent studies specifically on the corneal epithelial barrier, highlights of its structure, function and influence factors. (Chin J Ophthalmol, 2016, 52: 631-635). PMID:27562284

  3. Corneal cross-linking in 9 horses with ulcerative keratitis

    PubMed Central

    2013-01-01

    Background Corneal ulcers are one of the most common eye problems in the horse and can cause varying degrees of visual impairment. Secondary infection and protease activity causing melting of the corneal stroma are always concerns in patients with corneal ulcers. Corneal collagen cross-linking (CXL), induced by illumination of the corneal stroma with ultraviolet light (UVA) after instillation of riboflavin (vitamin B2) eye drops, introduces crosslinks which stabilize melting corneas, and has been used to successfully treat infectious ulcerative keratitis in human patients. Therefore we decided to study if CXL can be performed in sedated, standing horses with ulcerative keratitis with or without stromal melting. Results Nine horses, aged 1 month to 16 years (median 5 years) were treated with a combination of CXL and medical therapy. Two horses were diagnosed with mycotic, 5 with bacterial and 2 with aseptic ulcerative keratitis. A modified Dresden-protocol for CXL could readily be performed in all 9 horses after sedation. Stromal melting, diagnosed in 4 horses, stopped within 24 h. Eight of nine eyes became fluorescein negative in 13.5 days (median time; range 4–26 days) days after CXL. One horse developed a bacterial conjunctivitis the day after CXL, which was successfully treated with topical antibiotics. One horse with fungal ulcerative keratitis and severe uveitis was enucleated 4 days after treatment due to panophthalmitis. Conclusions CXL can be performed in standing, sedated horses. We did not observe any deleterious effects attributed to riboflavin or UVA irradiation per se during the follow-up, neither in horses with infectious nor aseptic ulcerative keratitis. These data support that CXL can be performed in the standing horse, but further studies are required to compare CXL to conventional medical treatment in equine keratitis and to optimize the CXL protocol in this species. PMID:23803176

  4. Reexpansion pulmonary edema in children

    PubMed Central

    Rodrigues, Antonio Lucas L.; Lopes, Carlos Eduardo; Romaneli, Mariana Tresoldi das N.; Fraga, Andrea de Melo A.; Pereira, Ricardo Mendes; Tresoldi, Antonia Teresinha

    2013-01-01

    OBJECTIVE To present a case of a patient with clinical and radiological features of reexpansion pulmonary edema, a rare and potentially fatal disease. CASE DESCRIPTION An 11-year-old boy presenting fever, clinical signs and radiological features of large pleural effusion initially treated as a parapneumonic process. Due to clinical deterioration he underwent tube thoracostomy, with evacuation of 3,000 mL of fluid; he shortly presented acute respiratory insufficiency and needed mechanical ventilation. He had an atypical evolution (extubated twice with no satisfactory response). Computerized tomography findings matched those of reexpansion edema. He recovered satisfactorily after intensive care, and pleural tuberculosis was diagnosed afterwards. COMMENTS Despite its rareness in the pediatric population (only five case reports gathered), the knowledge of this pathology and its prevention is very important, due to high mortality rates. It is recommended, among other measures, slow evacuation of the pleural effusion, not removing more than 1,500 mL of fluid at once. PMID:24142327

  5. Increased pulmonary vascular permeability as a cause of re-expansion edema in rabbits

    SciTech Connect

    Pavlin, D.J.; Nessly, M.L.; Cheney, F.W.

    1981-01-01

    In order to study the mechanism(s) underlying re-expansion edema, we measured the concentration of labeled albumin (RISA) in the extravascular, extracellular water (EVECW) of the lung as a measure of pulmonary vascular permeability. Re-expansion edema was first induced by rapid re-expansion of rabbit lungs that had been collapsed for 1 wk by pneumothorax. The RISA in EVECW was expressed as a fraction of its plasma concentration: (RISA)L/(RISA)PL. The volume of EVECW (ml/gm dry lung) was measured using a /sup 24/Na indicator. Results in re-expansion edema were compared with normal control lungs and with oleic acid edema as a model of permeability edema. In re-expanded lungs, EVECW (3.41 +/- SD 1.24 ml/g) and (RISA)L/(RISA)PL 0.84 +/- SD 0.15) were significantly increased when compared with normal control lungs (2.25 +/- 0.41 ml/g and 0.51 +/- 0.20, respectively). Results in oleic acid edema (5.66 +/- 2.23 ml/g and 0.84 +/- 0.23) were similar to re-expansion edema. This suggested that re-expansion edema is due to increased pulmonary vascular permeability caused by mechanical stresses applied to the lung during re-expansion.

  6. Progress in Drug Treatment of Cerebral Edema.

    PubMed

    Deng, Y Y; Shen, F C; Xie, D; Han, Q P; Fang, M; Chen, C B; Zeng, H K

    2016-01-01

    Cerebral edema causes intracranial hypertension (ICH) which leads to severe outcome of patients in the clinical setting. Effective anti-edema therapy may significantly decrease the mortality in a variety of neurological conditions. At present drug treatment is a cornerstone in the management of cerebral edema. Osmotherapy has been the mainstay of pharmacologic therapy. Mannitol and hypertonic saline (HS) are the most commonly used osmotic agents. The relative safety and efficacy of HS and mannitol in the treatment of cerebral edema and reduction of enhanced ICP have been demonstrated in the past decades. Apart from its osmotic force, HS exerts anti-edema effects partly through inhibition of Na(+)-K(+)-2Cl(-) Cotransporter-1 (NKCC1) and aquaporin 4 (AQP4) expression in astrocytes. Melatonin may also reduce brain edema and exert neuroprotective effect on several central nervous system diseases through inhibition of inflammatory response. The inhibitors of Na/H exchanger, NKCC and AQP4 may attenuate brain edema formation through inhibition of excessive transportation of ion and water from blood into the cerebral tissue. In this review we survey some of the most recent findings in the drug treatment of brain edema focusing on the use of osmotherapy, melatonin and inhibitors of ion cotransporters and water channels. A better understanding of the molecular mechanism of these agents would help to improve in the clinical management of patients with brain edema. PMID:26948324

  7. Ribonuclease 5 facilitates corneal endothelial wound healing via activation of PI3-kinase/Akt pathway

    PubMed Central

    Kim, Kyoung Woo; Park, Soo Hyun; Lee, Soo Jin; Kim, Jae Chan

    2016-01-01

    To maintain corneal transparency, corneal endothelial cells (CECs) exert a pump function against aqueous inflow. However, human CECs are arrested in the G1-phase and non-proliferative in vivo. Thus, treatment of corneal endothelial decompensation is limited to corneal transplantation, and grafts are vulnerable to immune rejection. Here, we show that ribonuclease (RNase) 5 is more highly expressed in normal human CECs compared to decompensated tissues. Furthermore, RNase 5 up-regulated survival of CECs and accelerated corneal endothelial wound healing in an in vitro wound of human CECs and an in vivo cryo-damaged rabbit model. RNase 5 treatment rapidly induced accumulation of cytoplasmic RNase 5 into the nucleus, and activated PI3-kinase/Akt pathway in human CECs. Moreover, inhibition of nuclear translocation of RNase 5 using neomycin reversed RNase 5-induced Akt activation. As a potential strategy for proliferation enhancement, RNase 5 increased the population of 5-bromo-2′-deoxyuridine (BrdU)-incorporated proliferating CECs with concomitant PI3-kinase/Akt activation, especially in CECs deprived of contact-inhibition. Specifically, RNase 5 suppressed p27 and up-regulated cyclin D1, D3, and E by activating PI3-kinase/Akt in CECs to initiate cell cycle progression. Together, our data indicate that RNase 5 facilitates corneal endothelial wound healing, and identify RNase 5 as a novel target for therapeutic exploitation. PMID:27526633

  8. Reversible Nerve Damage and Corneal Pathology in Murine Herpes Simplex Stromal Keratitis

    PubMed Central

    Yun, Hongmin; Rowe, Alexander M.; Lathrop, Kira L.; Harvey, Stephen A. K.

    2014-01-01

    associated loss of BR severely exacerbates and prolongs inflammation-induced pathology in mice. Preventing corneal desiccation results in a milder and more transient HSK with variable scarring that mirrors HSK seen in most humans. We further show that nerve damage is reversible and regulated by CD4+ T cells. Thus, we provide a mouse model that more closely resembles typical human HSK and suggest nerve damage is an important but largely overlooked factor in human disease. PMID:24789786

  9. Changes in Corneal Biomechanical Properties after Long-Term Topical Prostaglandin Therapy

    PubMed Central

    Yu, Xiaobo; Li, Mengwei; Wen, Wen; Sun, Xinghuai

    2016-01-01

    biomechanical parameters among the 3 types of PGA therapy subgroups, namely bimatoprost, latanoprost and travoprost. Conclusions Significant changes in corneal deformation parameters were found among untreated POAG patients, POAG patients with long-term topical PGA therapy and normal controls. Long-term topical PGA treatment might have a direct effect on corneal biomechanical properties in addition to the indirect effect owing to the PGA-induced IOP reduction and CCT decrease on corneal dynamic properties. PMID:27187282

  10. Surgical technique: coupling of intrastromal corneal ring segments for ectatic corneal disorders in eye bank corneas

    PubMed Central

    Moshirfar, Majid; Hsu, Maylon; Khalifa, Yousuf M

    2011-01-01

    The management of corneal ectasia is evolving, with intrastromal corneal ring segments playing an important role in delaying or eliminating the need for penetrating keratoplasty. This paper describes a modification in the implantation technique of intrastromal corneal ring segments that allows for coupling of the two segments with suture, affording more structural support. PMID:22034567

  11. Primary corneal melanocytoma in a Collie.

    PubMed

    Bauer, Bianca; Leis, Marina L; Sayi, Soraya

    2015-09-01

    A 6-year-old female, spayed Collie was referred to the Western College of Veterinary Medicine for a 12-month history of a progressive right corneal mass. A superficial keratectomy was performed and histopathology revealed a corneal melanocytoma with complete excision. There has been no recurrence of the neoplasm to date (12 months). This is the first known report of an isolated corneal melanocytoma in a canine. PMID:25296627

  12. Brillouin Microscopy of Collagen Crosslinking: Noncontact Depth-Dependent Analysis of Corneal Elastic Modulus

    PubMed Central

    Scarcelli, Giuliano; Kling, Sabine; Quijano, Elena; Pineda, Roberto; Marcos, Susana; Yun, Seok Hyun

    2013-01-01

    Purpose. Corneal collagen crosslinking (CXL) is designed to halt the progression of keratoconus and corneal ectasia by inducing corneal stiffening. However, it currently is difficult to monitor and evaluate CXL outcome objectively due to the lack of suitable methods to characterize corneal mechanical properties. We validated noncontact Brillouin microscopy to quantify corneal mechanical properties before and after CXL. Methods. CXL was performed on fresh porcine eyes using various presoaking times and light doses, with or without epithelial debridement. From Brillouin maps of corneal elastic modulus, stiffness and average modulus of anterior, middle, and posterior stroma were analyzed. Corneal stiffening index (CSI) was introduced as a metric to compare the mechanical efficacy of a given CXL protocol with respect to the standard protocol (30-minute riboflavin presoak, 3 mW/cm2 ultraviolet illumination for 30 minutes). Results. Brillouin corneal stiffness increased significantly (P < 0.001) by epi-off and epi-on CXL. The increase of Brillouin modulus was depth-dependent, indicating that anterior stromal stiffening contributes the most to mechanical outcome. The increase of anterior Brillouin modulus was linearly proportional to the light dose (R2 > 0.98). Compared to the standard epi-off procedure, a typical epi-on procedure resulted in a third of stiffness increase in porcine corneas (CSI = 33). Conclusions. Brillouin microscopy allowed imaging and quantifying CXL-induced mechanical changes without contact in a depth-dependent manner at high spatial resolution. This technique may be useful to evaluate the mechanical outcomes of CXL procedures, to compare different crosslinking agents, and for real-time monitoring of CXL in clinical and experimental settings. PMID:23361513

  13. Expression of Toll-Like Receptor 4 Contributes to Corneal Inflammation in Experimental Dry Eye Disease

    PubMed Central

    Lee, Hyun Soo; Hattori, Takaaki; Park, Eun Young; Stevenson, William; Chauhan, Sunil K.; Dana, Reza

    2012-01-01

    Purpose. To investigate the corneal expression of toll-like receptor (TLR) 4 and determine its contribution to the immunopathogenesis of dry eye disease (DED). Methods. Seven to 8-week-old female C57BL/6 mice were housed in a controlled environment chamber and administered scopolamine to induce experimental DED. Mice received intravenous TLR4 inhibitor (Eritoran) to block systemic TLR4-mediated activity. The expression of TLR4 by the corneal epithelium and stroma was evaluated using real-time polymerase chain reaction and flow cytometry. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease severity. The corneal expression of proinflammatory cytokines (IL-1β, IL-6, TNF, and CCL2), corneal infiltration of CD11b+ antigen-presenting cells, and lymph node frequency of mature MHC-IIhi CD11b+ cells were assessed. Results. The epithelial cells of normal corneas expressed TLR4 intracellularly; however, DED significantly increased the cell surface expression of TLR4. Similarly, flow cytometric analysis of stromal cells revealed a significant increase in the expression of TLR4 proteins by DED-induced corneas as compared with normal corneas. DED increased the mRNA expression of TLR4 in corneal stromal cells, but not epithelial cells. TLR4 inhibition decreased the severity of CFS and significantly reduced the mRNA expression of IL-1β, IL-6, and TNF. Furthermore, TLR4 inhibition significantly reduced the corneal infiltration of CD11b+ cells and the lymph node frequency of MHC-IIhi CD11b+ cells. Conclusions. These results suggest that DED increases the corneal expression of TLR4 and that TLR4 participates in the inflammatory response to ocular surface desiccating stress. PMID:22789921

  14. Optimization model for UV-Riboflavin corneal cross-linking

    NASA Astrophysics Data System (ADS)

    Schumacher, S.; Wernli, J.; Scherrer, S.; Bueehler, M.; Seiler, T.; Mrochen, M.

    2011-03-01

    Nowadays UV-cross-linking is an established method for the treatment of keraectasia. Currently a standardized protocol is used for the cross-linking treatment. We will now present a theoretical model which predicts the number of induced crosslinks in the corneal tissue, in dependence of the Riboflavin concentration, the radiation intensity, the pre-treatment time and the treatment time. The model is developed by merging the difussion equation, the equation for the light distribution in dependence on the absorbers in the tissue and a rate equation for the polymerization process. A higher concentration of Riboflavin solution as well as a higher irradiation intensity will increase the number of induced crosslinks. However, performed stress-strain experiments which support the model showed that higher Riboflavin concentrations (> 0.125%) do not result in a further increase in stability of the corneal tissue. This is caused by the inhomogeneous distribution of induced crosslinks throughout the cornea due to the uneven absorption of the UV-light. The new model offers the possibility to optimize the treatment individually for every patient depending on their corneal thickness in terms of efficiency, saftey and treatment time.

  15. Automated superficial lamellar keratectomy augmented by excimer laser masked PTK in the management of severe superficial corneal opacities

    PubMed Central

    Alio, J L; Javaloy, J; Merayo, J; Galal, A

    2004-01-01

    Aim: To assess superficial lamellar keratectomy augmented by excimer laser smoothening with sodium hyaluronate 0.25%, for the management of superficial corneal opacities. Methods: Consecutive procedure performed in 14 eyes (13 patients) with an automated microkeratome and excimer laser phototherapeutic keratectomy (PTK) smoothening using sodium hyaluronate 0.25%. Main outcome measures: UCVA, BCVA, pachymetry, degree of haze, ray tracing analysis, and complications. Mean follow up was 12 (SD 1.6) months. Results: Mean preoperative haze from previous corneal refractive surgeries was 3.5 (SD 0.5) (11/14 cases). In one case, opacity was caused by ocular trauma and in two by infectious keratitis. The mean preoperative UCVA was 0.7 logMAR (0.2 (SD 0.13) decimal value). BCVA was 0.4 logMAR (0.4 (SD 0.17) decimal value). Mean preoperative corneal pachymetry was 508 (SD 62.5) µm and mean opacity depth measured by corneal confocal microscopy was 115.2 (SD 49.4) µm. At 6 months, 71.4% of the eyes with previous corneal refractive surgery showed grade I haze or less. Mean postoperative corneal pachymetry at 6 months was 352.36 (SD 49.05) µm. Conclusions: Automated superficial lamellar keratectomy combined with excimer laser PTK smoothening assisted by sodium hyaluronate 0.25% induces a significant improvement of corneal transparency and visual acuity in cases of corneal opacity caused by previous refractive surgery, ocular trauma, and keratitis. PMID:15377553

  16. Central Corneal Thickness in Children

    PubMed Central

    2011-01-01

    Objective To report the central corneal thickness (CCT) in healthy white, African-American, and Hispanic children from birth to 17 years of age. Design Prospective observational multicenter study. Central corneal thickness was measured with a hand-held contact pachymeter. Results Two thousand seventy-nine children were included in the study, with ages ranging from day of birth to 17 years. Included were 807 white, 494 Hispanic, and 474 African-American individuals, in addition to Asian, unknown and mixed race individuals. African-American children had thinner corneas on average than that of both white (p< .001) and Hispanic children (p< .001) by approximately 20 micrometers. Thicker median CCT was observed with each successive year of age from age 1 to 11 years, with year-to-year differences steadily decreasing and reaching a plateau after age 11 at 573 micrometers in white and Hispanic children and 551 micrometers in African-American children. For every 100 micrometers of thicker CCT measured, the intraocular pressure was 1.5 mmHg higher on average (p< 0.001). For every diopter of increased myopic refractive error (p< 0.001) CCT was 1 micrometer thinner on average. Conclusions Median CCT increases with age from 1 to 11 years with the greatest increase present in the youngest age groups. African-American children on average have thinner central corneas than white and Hispanic children, while white and Hispanic children demonstrate similar central corneal thickness. PMID:21911662

  17. A Native-Like Corneal Construct Using Donor Corneal Stroma for Tissue Engineering

    PubMed Central

    Lin, Jing; Yoon, Kyung-Chul; Zhang, Lili; Su, Zhitao; Lu, Rong; Ma, Ping; De Paiva, Cintia S.; Pflugfelder, Stephen C.; Li, De-Quan

    2012-01-01

    Tissue engineering holds great promise for corneal transplantation to treat blinding diseases. This study was to explore the use of natural corneal stroma as an optimal substrate to construct a native like corneal equivalent. Human corneal epithelium was cultivated from donor limbal explants on corneal stromal discs prepared by FDA approved Horizon Epikeratome system. The morphology, phenotype, regenerative capacity and transplantation potential were evaluated by hematoxylin eosin and immunofluorescent staining, a wound healing model, and the xeno-transplantation of the corneal constructs to nude mice. An optically transparent and stratified epithelium was rapidly generated on donor corneal stromal substrate and displayed native-like morphology and structure. The cells were polygonal in the basal layer and became flattened in superficial layers. The epithelium displayed a phenotype similar to human corneal epithelium in vivo. The differentiation markers, keratin 3, involucrin and connexin 43, were expressed in full or superficial layers. Interestingly, certain basal cells were immunopositive to antibodies against limbal stem/progenitor cell markers ABCG2 and p63, which are usually negative in corneal epithelium in vivo. It suggests that this bioengineered corneal epithelium shared some characteristics of human limbal epithelium in vivo. This engineered epithelium was able to regenerate in 4 days following from a 4mm-diameter wound created by a filter paper soaked with 1 N NaOH. This corneal construct survived well after xeno-transplantation to the back of a nude mouse. The transplanted epithelium remained multilayer and became thicker with a phenotype similar to human corneal epithelium. Our findings demonstrate that natural corneal stroma is an optimal substrate for tissue bioengineering, and a native-like corneal construct has been created with epithelium containing limbal stem cells. This construct may have great potential for clinical use in corneal

  18. Transplantation of tissue-engineered human corneal endothelium in cat models

    PubMed Central

    Ma, Xiya; Zhao, Jun; Wen, Qian; Hu, Xiuzhong; Yu, Haoze; Shi, Weiyun

    2013-01-01

    Purpose To evaluate the performance of reconstructed tissue-engineered human corneal endothelium (TE-HCE) by corneal transplantation in cat models. Methods TE-HCE reconstruction was performed by culturing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled monoclonal HCE cells on denuded amniotic membranes (dAMs) in 20% fetal bovine serum-containing Dulbecco’s Modified Eagle’s Medium/Ham’s Nutrient Mixture F12 (1:1) medium and 5% CO2 at 37 °C on a 24-well culture plate. The reconstructed TE-HCE was transplanted into cat corneas via lamellar keratoplasty with all of the endothelium and part of Descemet’s membrane stripped. Postsurgical corneas were monitored daily with their histological properties examined during a period of 104 days after transplantation. Results The reconstructed TE-HCE at a density of 3,413.33±111.23 cells/mm2 in average established intense cell-cell and cell-dAM junctions. After lamellar keratoplasty surgery, no obvious edema was found in TE-HCE-transplanted cat corneas, which were transparent throughout the monitoring period. In contrast, intense corneal edema developed in dAM-transplanted cat corneas, which were turbid. The corneal thickness gradually decreased to 751.33±11.37 μm on day 104 after TE-HCE transplantation, while that of dAM eye was over 1,000 μm in thickness during the monitoring period. A monolayer of endothelium consisting of TE-HCE-originated cells at a density of 2,573.33±0.59 cells/mm2 attached tightly to the surface of remnant Descemet’s membrane over 104 days; this was similar to the normal eye control in cell density. Conclusions The reconstructed TE-HCE was able to function as a corneal endothelium equivalent and restore corneal function in cat models. PMID:23441111

  19. Functional TRPV1 expression in human corneal fibroblasts.

    PubMed

    Yang, Yuanquan; Yang, Hua; Wang, Zheng; Mergler, Stefan; Wolosin, J Mario; Reinach, Peter S

    2013-02-01

    Corneal wound healing in mice subsequent to an alkali burn results in dysregulated inflammation and opacification. Transient receptor potential vanilloid subtype 1 (TRPV1) channel activation in all tissue layers by endogenous ligands contributes to this sight compromising outcome since in TRPV1 knockout mice wound healing results instead in tissue transparency restoration. However, it is not known if primary human stromal fibroblasts exhibit such expression even though functional TRPV1 expression is evident in an immortalized human corneal epithelial cell line. In primary human corneal fibroblasts (HCF), TRPV1 gene expression and localization were identified based on the results of quantitative RT-PCR and immunocytochemistry, respectively. Western blot analysis identified a 100 kD protein corresponding to TRPV1 protein expression in a positive control. Single-cell fluorescence imaging detected in fura2-AM loaded cells Ca(2+) transients that rose 1.8-fold above the baseline induced by a selective TRPV1 agonist, capsaicin (CAP), which were blocked by a TRPV1 antagonist, capsazepine (CPZ) or exposure to a Ca(2+) free medium. The whole-cell mode of the planar patch-clamp technique identified TRPV1-induced currents that rose 1.76-fold between -60 and +130 mV. CAP-induced time dependent changes in the phosphorylation status of mitogen activated protein kinase (MAPK) signaling mediators that led to a 2.5-fold increase in IL-6 release after 24 h. This rise did not occur either in TRPV1 siRNA gene silenced cells or during exposure to SB203580 (10 μM), a selective p38 MAPK inhibitor. Taken together, identification of functional TRPV1 expression in HCF suggests that in vivo its activation by injury contributes to corneal opacification and inflammation during wound healing. These undesirable effects may result in part from increases in IL-6 expression mediated by p-p38 MAPK signaling. PMID:23232207

  20. RGTA-based matrix therapy in severe experimental corneal lesions: safety and efficacy studies.

    PubMed

    Brignole-Baudouin, F; Warnet, J M; Barritault, D; Baudouin, C

    2013-11-01

    Corneal alteration potentially leading to ulceration remains a major health concern in ocular surface diseases. A treatment that would improve both the quality and speed of healing and control the inflammation would be of great interest. Regenerating agents (RGTAs) have been shown to stimulate wound healing and modulate undesired fibrosis in various in vivo systems. We investigated the effects of RGTA-OTR4120(®) in a rabbit corneal model in order to assess its potential use in ocular surface diseases. First, we assessed its safety for 7 and 28 days using the Draize test criteria in healthy rabbit eyes; then, we investigated the effect of a single dose (50μl, 5μg) in an alkali-burned cornea model. Daily follow-up of clinical signs of healing was scored, and histology was performed at D7. RGTA was well tolerated; no signs of ocular irritation were observed. In the corneal alkali-burn model, non-RGTA-treated eyes showed inflammatory clinical signs, and histology confirmed a loss of superficial corneal layers with epithelial disorganization, neovascularization and infiltration of inflammatory cells. When compared to NaCl control, RGTA treatment appeared effective in reducing clinical signs of inflammation, enhancing re-epithelialization, and improving histological patterns: edema, fibrosis, neovascularization and inflammation. Three to four layers of epithelial cells were already organized, stroma was virtually unvascularized and keratocytes well implanted in parallel collagen fibers with an overall reorganization similar to normal cornea. RGTA appears to be a promising agent for controlling ocular surface inflammation and promoting corneal healing and was well tolerated. This study offers preclinical information and supports the findings of other (compassionate or pilot) studies conducted in patients with various ocular surface diseases. PMID:23958066

  1. Reinke Edema: Watch For Vocal Fold Cysts.

    PubMed

    Tüzüner, Arzu; Demirci, Sule; Yavanoglu, Ahmet; Kurkcuoglu, Melih; Arslan, Necmi

    2015-06-01

    Reinke edema is one of the common cause of dysphonia middle-aged population, and severe thickening of vocal folds require surgical treatment. Smoking plays a major role on etiology. Vocal fold cysts are also benign lesions and vocal trauma blamed for acquired cysts. We would like to present 3 cases with vocal fold cyst related with Reinke edema. First case had a subepidermal epidermoid cyst with Reinke edema, which could be easily observed before surgery during laryngostroboscopy. Second case had a mucous retention cyst into the edematous Reinke tissue, which was detected during surgical intervention, and third case had a epidermoid cyst that occurred 2 months after before microlaryngeal operation regarding Reinke edema reduction. These 3 cases revealed that surgical management of Reinke edema needs a careful dissection and close follow-up after surgery for presence of vocal fold cysts. PMID:26080256

  2. Benzalkonium Chloride Accelerates the Formation of the Amyloid Fibrils of Corneal Dystrophy-associated Peptides*

    PubMed Central

    Kato, Yusuke; Yagi, Hisashi; Kaji, Yuichi; Oshika, Tetsuro; Goto, Yuji

    2013-01-01

    Corneal dystrophies are genetic disorders resulting in progressive corneal clouding due to the deposition of amyloid fibrils derived from keratoepithelin, also called transforming growth factor β-induced protein (TGFBI). The formation of amyloid fibrils is often accelerated by surfactants such as sodium dodecyl sulfate (SDS). Most eye drops contain benzalkonium chloride (BAC), a cationic surfactant, as a preservative substance. In the present study, we aimed to reveal the role of BAC in the amyloid fibrillation of keratoepithelin-derived peptides in vitro. We used three types of 22-residue synthetic peptides covering Leu110-Glu131 of the keratoepithelin sequence: an R-type peptide with wild-type R124, a C-type peptide with C124 associated with lattice corneal dystrophy type I, and a H-type peptide with H124 associated with granular corneal dystrophy type II. The time courses of spontaneous amyloid fibrillation and seed-dependent fibril elongation were monitored in the presence of various concentrations of BAC or SDS using thioflavin T fluorescence. BAC and SDS accelerated the fibrillation of all synthetic peptides in the absence and presence of seeds. Optimal acceleration occurred near the CMC, which suggests that the unstable and dynamic interactions of keratoepithelin peptides with amphipathic surfactants led to the formation of fibrils. These results suggest that eye drops containing BAC may deteriorate corneal dystrophies and that those without BAC are preferred especially for patients with corneal dystrophies. PMID:23861389

  3. In vivo Confocal Microscopy Report after Lasik with Sequential Accelerated Corneal Collagen Cross-Linking Treatment

    PubMed Central

    Mazzotta, Cosimo; Balestrazzi, Angelo; Traversi, Claudio; Caragiuli, Stefano; Caporossi, Aldo

    2014-01-01

    We report the first pilot qualitative confocal microscopic analysis of a laser in situ keratomileusis (Lasik) treatment combined with sequential high-fluence accelerated corneal collagen cross-linking, denominated Lasik XTra, by means of HRT II laser scanning in vivo confocal microscopy after a 6-month follow-up. After obtaining approval from the Siena University Hospital Institutional Review Board, a 33-year-old female patient underwent a Lasik XTra procedure in her left eye. Confocal analysis demonstrated induced slight corneal microstructural changes by the interaction between UV-A, riboflavin and corneal stromal collagen, beyond the interface to a depth of 160 µm, without adverse events at the interface and endothelial levels. This application may be considered a prophylactic biomechanical treatment, stiffening the intermediate corneal stroma to prevent corneal ectasia and stabilizing the clinical results of refractive surgery. According to our preliminary experiences, this combined approach may be useful in higher-risk Lasik patients for hyperopic treatments, high myopia and lower corneal thicknesses. PMID:24847258

  4. Decay accelerating factor is essential for successful corneal engraftment

    PubMed Central

    Esposito, Andrew; Suedekum, Brandon; Liu, Jinbo; An, Fengqi; Lass, Jonathan; Strainic, Michael G; Lin, Feng; Heeger, Peter; Medof, M. Edward

    2012-01-01

    In contrast to immune restrictions that pertain for solid organ transplants, the tolerogenic milieu of the eye permits successful corneal transplantation without systemic immunosuppression, even across a fully MHC disparate barrier. Here we show that recipient and donor expression of decay accelerating factor (DAF or CD55), a cell surface C3/C5 convertase regulator recently shown to modulate T cell responses, is essential to sustain successful corneal engraftment. Whereas wild type (WT) corneas transplanted into multiple minor histocompatibility antigen (mH), or HY disparate WT recipients were accepted, DAF’s absence on either the donor cornea or in the recipient bed induced rapid rejection. Donor or recipient DAF deficiency led to expansion of donor-reactive IFN-γ producing CD4+ and CD8+ T cells, as well as inhibition of antigen induced IL-10 and TGF-β, together demonstrating that DAF deficiency precludes immune tolerance. In addition to demonstrating a requisite role for DAF in conferring ocular immune privilege, these results raise the possibility that augmenting DAF levels on corneal endothelium and/or the recipient bed could have therapeutic value for transplants that clinically are at high risk for rejection. PMID:20055803

  5. Self inflicted corneal abrasions due to delusional parasitosis

    PubMed Central

    Meraj, Adeel; Din, Amad U; Larsen, Lynn; Liskow, Barry I

    2011-01-01

    The authors report a case of self inflicted bilateral corneal abrasions and skin damage due to ophthalmic and cutaneous delusional parasitosis. A male in his 50s presented with a 10 year history of believing that parasites were colonizing his skin and biting into his skin and eyes. The patient had received extensive medical evaluations that found no evidence that symptoms were due to a medical cause. He was persistent in his belief and had induced bilateral corneal abrasions and skin damage by using heat lamps and hair dryers in an attempt to disinfect his body. The patient was treated with olanzapine along with treatment for his skin and eyes. His delusional belief system persisted but no further damage to his eyes and skin was noted on initial follow-up. PMID:22689836

  6. Corneal hysteresis and its relevance to glaucoma

    PubMed Central

    Deol, Madhvi; Taylor, David A.; Radcliffe, Nathan M.

    2015-01-01

    Purpose of review Glaucoma is a leading cause of irreversible blindness worldwide. It is estimated that roughly 60.5 million people had glaucoma in 2010 and that this number is increasing. Many patients continue to lose vision despite apparent disease control according to traditional risk factors. The purpose of this review is to discuss the recent findings with regard to corneal hysteresis, a variable that is thought to be associated with the risk and progression of glaucoma. Recent findings Low corneal hysteresis is associated with optic nerve and visual field damage in glaucoma and the risk of structural and functional glaucoma progression. In addition, hysteresis may enhance intraocular pressure (IOP) interpretation: low corneal hysteresis is associated with a larger magnitude of IOP reduction following various glaucoma therapies. Corneal hysteresis is dynamic and may increase in eyes after IOP-lowering interventions are implemented. Summary It is widely accepted that central corneal thickness is a predictive factor for the risk of glaucoma progression. Recent evidence shows that corneal hysteresis also provides valuable information for several aspects of glaucoma management. In fact, corneal hysteresis may be more strongly associated with glaucoma presence, risk of progression, and effectiveness of glaucoma treatments than central corneal thickness. PMID:25611166

  7. 21 CFR 886.1220 - Corneal electrode.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Corneal electrode. 886.1220 Section 886.1220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1220 Corneal electrode. (a) Identification. A...

  8. [Corneal tatoo--art or science?].

    PubMed

    Craiu, Andreea-Madalina

    2009-01-01

    The permanent colouring of disfigured corneal scars is known for almost 200 years. Because of improvement in surgical reconstructive techniques, corneal tattoing is used today only with a restricted group on carefully chosen patients, and merely for esthetique reasons. PMID:19697848

  9. Gamma delta T Cells Are Necessary for Platelet and Neutrophil Accumulation in Limbal Vessels and Efficient Epithelial Repair after Corneal Abrasion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Corneal epithelial abrasion in C57BL/6 mice induces an inflammatory response, with peak accumulation of neutrophils in the corneal stroma within 12 hours. Platelets localize in the limbal vessels throughout the same time course as neutrophils and contribute to wound healing because antibody-dependen...

  10. Extremely varied phenotypes in granular corneal dystrophy type 2 heterozygotes

    PubMed Central

    Han, Kyung Eun; Choi, Seung-il; Chung, Woo Suk; Jung, Se Hwan; Katsanis, Nicholas; Kim, Tae-im

    2012-01-01

    Purpose To investigate the phenotypic variability of patients bearing the heterozygous R124H mutation in the TGFBI (transforming growth factor-beta-induced) gene that causes granular corneal dystrophy type 2 (GCD2). Methods We describe the phenotypic range of GCD2 heterozygotes for the common R124H mutation in TGFBI; seven with an extremely mild phenotype and six with an extremely severe phenotype. Detailed slit-lamp photographs of these patients were generated. All patients had no history of ocular surgery and were diagnosed as being heterozygous for GCD2 by DNA analysis from peripheral blood. Expression levels of transforming growth factor-beta-induced protein (TGFBIp) were compared among cultured corneal fibroblasts from ten normal donors. Results We report profound differences in the severity of the phenotype across our case series. Two patients with a mild phenotype were diagnosed as unaffected at presentation; however follow-up examinations revealed granular deposits. Importantly, we also observed familial clustering of phenotypic variance; five patients from two families with a mild phenotype showed a similarly mild phenotype within family members. Similarly, six patients from two families with severe phenotypes showed corneal deposits with similar patterns and severity within each distinct family, but distinct patterns between families. TGFBIp expressions from different donor derived cultured corneal fibroblasts were different between one another. Conclusions GCD2 heterozygotes have extremely varied phenotypes between individual patients. However phenotypes were broadly consistent within families, suggesting that the observed variable expressivity might be regulated by other genetic factors that could influence the abundance of TGFBIp or the function of the pathway. From a clinical perspective, our data also highlighted that genetic analysis and meticulous slit-lamp examination in both eyes at multiple time intervals is necessary. PMID:22815629

  11. Corneal autofluorescence in presence of diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Rovati, Luigi; Docchio, Franco; Azzolini, Claudio; Van Best, Jaap A.

    1998-06-01

    Recently corneal autofluorescence has been proposed as an ocular diagnostic tool for diabetic retinopathy. The method is based on the sensible increase of the natural fluorescence of corneal tissue within specific wavelength in presence of early stage of diabetic retinopathy. The main advantages of this method are that the corneal autofluorescence has been demonstrated to be not age-related and that the cornea is readily accessible to be investigated. In this study 47 insulin-dependent diabetes mellitus and 51 non-insulin- dependent diabetes mellitus patients aged 20 - 90 years have been considered. Patients were selected from the Eye Clinic of S. Raffaele Hospital. The modified Airlie House classification was used to grade the diabetic retinopathy. Corneal autofluorescence has been measured by using both a specifically designed instrument and the Fluorotron Master. Corneal autofluorescence mean value for each diabetic retinopathy measured by using both the instruments correlated with the retinopathy grade.

  12. Riboflavin for corneal cross-linking.

    PubMed

    O'Brart, D P S

    2016-06-01

    Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A (UVA) radiation is the first therapeutic modality that appears to arrest the progression of keratoconus and other corneal ectasias. Riboflavin is central to the process, acting as a photosensitizer for the production of oxygen singlets and riboflavin triplets. These free radicals drive the CXL process within the proteins of the corneal stroma, altering its biomechanical properties. Riboflavin also absorbs the majority of the UVA radiation, which is potentially cytotoxic and mutagenic, within the anterior stroma, preventing damage to internal ocular structures, such as the corneal endothelium, lens and retina. Clinical studies report cessation of ectatic progression in over 90% of cases and the majority document significant improvements in visual, keratometric and topographic parameters. Clinical follow-up is limited to 5-10 years, but suggests sustained stability and enhancement in corneal shape. Sight-threatening complications are rare. The optimal stromal riboflavin dosage for CXL is as yet undetermined. PMID:27458610

  13. Corneal abrasions associated with pepper spray exposure.

    PubMed

    Brown, L; Takeuchi, D; Challoner, K

    2000-05-01

    Pepper spray containing oleoresin capsicum is used by law enforcement and the public as a form of nonlethal deterrent. Stimulated by the identification of a case of a corneal abrasion associated with pepper spray exposure, a descriptive retrospective review of a physician-maintained log of patients presenting to a jail ward emergency area over a 3-year period was performed. The objective was to give some quantification to the frequency with which an emergency physician could expect to see corneal abrasions associated with pepper spray exposure. Of 100 cases of pepper spray exposure identified, seven patients had sustained corneal abrasions. We conclude that corneal abrasions are not rare events when patients are exposed to pepper spray and that fluorescein staining and slit lamp or Wood's lamp examination should be performed on all exposed patients in whom corneal abrasions cannot be excluded on clinical grounds. PMID:10830682

  14. Corneal endothelium: developmental strategies for regeneration

    PubMed Central

    Zavala, J; López Jaime, G R; Rodríguez Barrientos, C A; Valdez-Garcia, J

    2013-01-01

    The main treatment available for restoration of the corneal endothelium is keratoplasty. This procedure is faced with several difficulties, including the shortage of donor tissue, post-surgical complications associated with the use of drugs to prevent immune rejection, and a significant increase in the occurrence of glaucoma. Recently, surgical procedures such as Descemet's stripping endothelial keratoplasty have focused on the transplant of corneal endothelium, yielding better visual results but still facing the need for donor tissue. The emergent strategies in the field of cell biology and tissue cultivation of corneal endothelial cells aim at the production of transplantable endothelial cell sheets. Cell therapy focuses on the culture of corneal endothelial cells retrieved from the donor, in the donor's cornea, followed by transplantation into the recipient. Recently, research has focused on overcoming the challenge of harvesting human corneal endothelial cells and the generation of new biomembranes to be used as cell scaffolds in surgical procedures. The use of corneal endothelial precursors from the peripheral cornea has also demonstrated to be effective and represents a valuable tool for reducing the risk of rejection in allogeneic transplants. Several animal model reports also support the use of adult stem cells as therapy for corneal diseases. Current results represent important progresses in the development of new strategies based on alternative sources of tissue for the treatment of corneal endotheliopathies. Different databases were used to search literature: PubMed, Google Books, MD Consult, Google Scholar, Gene Cards, and NCBI Books. The main search terms used were: ‘cornea AND embryology AND transcription factors', ‘human endothelial keratoplasty AND risk factors', ‘(cornea OR corneal) AND (endothelium OR endothelial) AND cell culture', ‘mesenchymal stem cells AND cell therapy', ‘mesenchymal stem cells AND cornea', and ‘stem cells AND

  15. Differential diagnosis of Schnyder corneal dystrophy.

    PubMed

    Weiss, Jayne S; Khemichian, Arbi J

    2011-01-01

    Schnyder corneal dystrophy (SCD) is a rare corneal dystrophy characterized by abnormally increased deposition of cholesterol and phospholipids in the cornea leading to progressive vision loss. SCD is inherited as an autosomal dominant trait with high penetrance and has been mapped to the UBIAD1 gene on chromosome 1p36.3. Although 2/3 of SCD patients also have systemic hypercholesterolemia, the incidence of hypercholesterolemia is also increased in unaffected members of SCD pedigrees. Consequently, SCD is thought to result from a local metabolic defect in the cornea. The corneal findings in SCD are very predictable depending on the age of the individual, with initial central corneal haze and/or crystals, subsequent appearance of arcus lipoides in the third decade and formation of midperipheral haze in the late fourth decade. Because only 50% of affected patients have corneal crystals, the International Committee for Classification of Corneal Dystrophies recently changed the original name of this dystrophy from Schnyder crystalline corneal dystrophy to Schnyder corneal dystrophy. Diagnosis of affected individuals without crystalline deposits is often delayed and these individuals are frequently misdiagnosed. The differential diagnosis of the SCD patient includes other diseases with crystalline deposits such as cystinosis, tyrosinemia, Bietti crystalline dystrophy, hyperuricemia/gout, multiple myeloma, monoclonal gammopathy, infectious crystalline keratopathy, and Dieffenbachia keratitis. Depositions from drugs such as gold in chrysiasis, chlorpromazine, chloroquine, and clofazamine can also result in corneal deposits and are different from SCD. Diseases of systemic lipid metabolism that cause corneal opacification, such as lecithin-cholesterol acyltransferase deficiency, fish eye disease and Tangier disease, should also be considered although these are autosomal recessive disorders. PMID:21540632

  16. Myocardial edema and compromised left ventricular function attributable to dirofilariasis and cardiopulmonary bypass in dogs.

    PubMed

    Rohn, D A; Davis, K L; Mehlhorn, U; Allen, S J; Laine, G A

    1995-02-01

    We investigated the relation between left ventricular dysfunction and myocardial edema in dogs with heartworm (Dirofilaria immitis) infection that were undergoing cardiopulmonary bypass. Dogs with and without D immitis were anesthetized by continuous thiopental infusion and were mechanically ventilated. Sonomicrometry crystals were placed on the long and short axes of the left ventricle, and a Millar pressure transducer was placed in the left ventricular chamber. Pressure-volume loops were digitized and continuously recorded. Dogs with and without D immitis were placed on standard hypothermic cardiopulmonary bypass, with 1 hour of aortic cross-clamp. Wet-to-dry weight ratio corrected for residual blood volume was used to quantitate the volume of myocardial edema. Preload recruitable stroke work was used as a preload-independent index of systolic function. Tau, the isovolumic relaxation time constant, was determined to assess diastolic relaxation. Dogs with D immitis had increased baseline myocardial wet-to-dry weight ratio. After cardiopulmonary bypass, myocardial edema increased in all dogs. Acute edema attributable to cardiopulmonary bypass decreased preload recruitable stroke work in all dogs of both groups, and dogs with D immitis could not be weaned from cardiopulmonary bypass. Myocardial edema increased diastolic relaxation times (tau) in dogs with and without D immitis. We conclude that cardiopulmonary bypass and heartworm infection induce myocardial edema. This edema compromises left ventricular systolic and diastolic function making D immitis an important confounding factor in weaning dogs from cardiopulmonary bypass. PMID:7717590

  17. Corneal Regeneration by Deep Anterior Lamellar Keratoplasty (DALK) Using Decellularized Corneal Matrix

    PubMed Central

    Hashimoto, Yoshihide; Funamoto, Seiichi; Sasaki, Shuji; Negishi, Jun; Honda, Takako; Hattori, Shinya; Nam, Kwangwoo; Kimura, Tsuyoshi; Mochizuki, Manabu; Kobayashi, Hisatoshi; Kishida, Akio

    2015-01-01

    The purpose of this study is to demonstrate the feasibility of DALK using a decellularized corneal matrix obtained by HHP methodology. Porcine corneas were hydrostatically pressurized at 980 MPa at 10°C for 10 minutes to destroy the cells, followed by washing with EGM-2 medium to remove the cell debris. The HHP-treated corneas were stained with H-E to assess the efficacy of decellularization. The decellularized corneal matrix of 300 μm thickness and 6.0 mm diameter was transplanted onto a 6.0 mm diameter keratectomy wound. The time course of regeneration on the decellularized corneal matrix was evaluated by haze grading score, fluorescein staining, and immunohistochemistry. H-E staining revealed that no cell nuclei were observed in the decellularized corneal matrix. The decellularized corneal matrices were opaque immediately after transplantation, but became completely transparent after 4 months. Fluorescein staining revealed that initial migration of epithelial cells over the grafts was slow, taking 3 months to completely cover the implant. Histological sections revealed that the implanted decellularized corneal matrix was completely integrated with the receptive rabbit cornea, and keratocytes infiltrated into the decellularized corneal matrix 6 months after transplantation. No inflammatory cells such as macrophages, or neovascularization, were observed during the implantation period. The decellularized corneal matrix improved corneal transparency, and remodelled the graft after being transplanted, demonstrating that the matrix obtained by HHP was a useful graft for corneal tissue regeneration. PMID:26161854

  18. Radiosurgery for brain metastases and cerebral edema.

    PubMed

    Gazit, Inbal; Har-Nof, Sagi; Cohen, Zvi R; Zibly, Zion; Nissim, Uzi; Spiegelmann, Roberto

    2015-03-01

    The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010-2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9 years. During the 2 months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6 mg/day, the mean metastasis volume decreased from 3.79±4.12 cc to 2.8±4.48 cc (p=0.001), and the mean edema volume decreased from 16.91±30.15 cc to 12.85±24.47 cc (p=0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change <10%, 0-2 cc) and increased in four patients (by >10%, 2-14 cc). In a subanalysis of eight metastases with baseline edema volume greater than 40 cc, edema volume decreased from 77.27±37.21 cc to 24.84±35.6 cc (p=0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids. PMID:25533053

  19. Impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

    PubMed Central

    Chen, Zhe (Jay); Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

    2011-01-01

    Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days

  20. The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

    NASA Astrophysics Data System (ADS)

    (Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

    2011-08-01

    Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than

  1. ALDH3A1 Plays a Functional Role in Maintenance of Corneal Epithelial Homeostasis

    PubMed Central

    Mehta, Gaurav; Orlicky, David J.; Thompson, David C.; Jester, James V.; Vasiliou, Vasilis

    2016-01-01

    Aldehyde dehydrogenase 1A1 (ALDH1A1) and ALDH3A1 are corneal crystallins. They protect inner ocular tissues from ultraviolet radiation (UVR)-induced oxidative damage through catalytic and non-catalytic mechanisms. Additionally, ALDH3A1 has been postulated to play a regulatory role in the corneal epithelium based on several studies that report an inverse association between ALDH3A1 expression and corneal cell proliferation. The underlying molecular mechanisms and the physiological significance of such association remain poorly understood. In the current study, we established Tet-On human corneal epithelial cell (hTCEpi) lines, which express tetracycline-inducible wild-type (wt) or catalytically-inactive (mu) ALDH3A1. Utilizing this cellular model system, we confirmed that human ALDH3A1 decreases corneal cell proliferation; importantly, this effect appears to be partially mediated by its enzymatic activity. Mechanistically, wt-ALDH3A1, but not mu-ALDH3A1, promotes sequestering of tumor suppressor p53 in the nucleus. In the mouse cornea, however, augmented cell proliferation is noted only in Aldh1a1-/-/3a1-/- double knockout (DKO) mice, indicating in vivo the anti-proliferation effect of ALDH3A1 can be rescued by the presence of ALDH1A1. Interestingly, the hyper-proliferative epithelium of the DKO corneas display nearly complete loss of p53 expression, implying that p53 may be involved in ALDH3A1/1A1-mediated effect. In hTCEpi cells grown in high calcium concentration, mRNA levels of a panel of corneal differentiation markers were altered by ALDH3A1 expression and modulated by its enzyme activity. In conclusion, we show for the first time that: (i) ALDH3A1 decreases corneal epithelial proliferation through both non-enzymatic and enzymatic properties; (ii) ALDH1A1 contributes to the regulation of corneal cellular proliferation in vivo; and (iii) ALDH3A1 modulates corneal epithelial differentiation. Collectively, our studies indicate a functional role of ALDH3A1 in the

  2. Melatonin lowers edema after spinal cord injury

    PubMed Central

    Li, Cheng; Chen, Xiao; Qiao, Suchi; Liu, Xinwei; Liu, Chang; Zhu, Degang; Su, Jiacan; Wang, Zhiwei

    2014-01-01

    Melatonin has been shown to diminish edema in rats. Melatonin can be used to treat spinal cord injury. This study presumed that melatonin could relieve spinal cord edema and examined how it might act. Our experiments found that melatonin (100 mg/kg, i.p.) could reduce the water content of the spinal cord, and suppress the expression of aquaporin-4 and glial fibrillary acidic protein after spinal cord injury. This suggests that the mechanism by which melatonin alleviates the damage to the spinal cord by edema might be related to the expression of aquaporin-4 and glial fibrillary acidic protein. PMID:25657743

  3. Evaluating the potential role of nitric oxide as a mediator of hydrostatic edema mediated intestinal contractile dysfunction

    PubMed Central

    Shah, Shinil K.; Xue, Hasen; Jimenez, Fernando; Kots, Alexander Y.; Choi, Byung-Kwon; Uray, Karen S.; Walker, Peter A.; Moore-Olufemi, Stacey D.; Velez, Natalia; Stewart, Randolph H.; Laine, Glen A.; Cox, Charles S.

    2010-01-01

    Background Administration of L-nil, a selective inhibitor of inducible nitric oxide synthase (iNOS), improves ileus in an animal model of resuscitation induced intestinal edema. The purpose of this study was to elucidate the iNOS/nitric oxide (NO) signal transduction pathway in intestinal edema. Materials and Methods Male Sprague Dawley rats were divided into two groups; CONTROL and RESUS + VH (edema, 80cc/kg normal saline (resuscitation) with mesenteric venous hypertension). iNOS mRNA and protein, iNOS activity, NO tissue levels, soluble guanylyl cyclase (sGC) expression, and cyclic guanosine monophosphate (cGMP) levels were measured. As a functional endpoint, we evaluated intestinal contractile strength and frequency in L-nil treated animals. Results Edema was associated with increased iNOS mRNA and protein expression without subsequent increases in iNOS activity or tissue NO levels. There was no significant change in sGC expression or increase in cGMP induced by edema. Administration of L-nil did not decrease edema development or preserve contractile strength, but increased contractile frequency. Conclusion Hydrostatic intestinal edema is not associated with increased iNOS activity or tissue NO levels. Administration of L-nil in edema increases intestinal contractile frequency. This may represent a potential mechanism for the amelioration of ileus seen with the administration of L-nil. PMID:20605598

  4. Corneal modeling for analysis of photorefractive keratectomy

    NASA Astrophysics Data System (ADS)

    Della Vecchia, Michael A.; Lamkin-Kennard, Kathleen

    1997-05-01

    Procedurally, excimer photorefractive keratectomy is based on the refractive correction of composite spherical and cylindrical ophthalmic errors of the entire eye. These refractive errors are inputted for correction at the corneal plane and for the properly controlled duration and location of laser energy. Topography is usually taken to correspondingly monitor spherical and cylindrical corneorefractive errors. While a corneal topographer provides surface morphologic information, the keratorefractive photoablation is based on the patient's spherical and cylindrical spectacle correction. Topography is at present not directly part of the procedural deterministic parameters. Examination of how corneal curvature at each of the keratometric reference loci affect the shape of the resultant corneal photoablated surface may enhance the accuracy of the desired correction. The objective of this study was to develop a methodology to utilize corneal topography for construction of models depicting pre- and post-operative keratomorphology for analysis of photorefractive keratectomy. Multiple types of models were developed then recreated in optical design software for examination of focal lengths and other optical characteristics. The corneal models were developed using data extracted from the TMS I corneal modeling system (Computed Anatomy, New York, NY). The TMS I does not allow for manipulation of data or differentiation of pre- and post-operative surfaces within its platform, thus models needed to be created for analysis. The data were imported into Matlab where 3D models, surface meshes, and contour plots were created. The data used to generate the models were pre- and post-operative curvatures, heights from the corneal apes, and x-y positions at 6400 locations on the corneal surface. Outlying non-contributory points were eliminated through statistical operations. Pre- and post- operative models were analyzed to obtain the resultant changes in the corneal surfaces during PRK

  5. First Identification of a Triple Corneal Dystrophy Association: Keratoconus, Epithelial Basement Membrane Corneal Dystrophy and Fuchs’ Endothelial Corneal Dystrophy

    PubMed Central

    Mazzotta, Cosimo; Traversi, Claudio; Raiskup, Frederik; Rizzo, Caterina Lo; Renieri, Alessandra

    2014-01-01

    Purpose To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs’ endothelial corneal dystrophy (FECD). Methods A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing. Results Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman's layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1. Conclusion This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy. PMID:25408666

  6. Comparative analysis of corneal morphological changes after transversal and torsional phacoemulsification through 2.2 mm corneal incision

    PubMed Central

    Assaf, Ahmed; Roshdy, Maged Maher

    2013-01-01

    Purpose This paper compares and evaluates the corneal morphological changes occurring after cataract surgery through a 2.2 mm corneal incision. We use two platforms for comparison and evaluation, transversal and torsional phacoemulsification. Patients and methods This study includes 139 consecutive cataractous eyes (nuclear color 2–4, according to the Lens Opacities Classification System III [LOCSIII]) of 82 patients undergoing cataract surgery through a 2.2 mm corneal incision. Two different phacoemulsification platforms were used and assigned randomly: we used the WhiteStar Signature® system with the Ellips™ FX transversal continuous ultrasound (US) mode for group I (mean age: 65.33 ± 6.97 years), and we used the Infiniti® system with the OZil® Intelligent Phaco (IP) torsional US mode for group II (mean age: 64.02 ± 7.55 years). The corneal endothelium and pachymetry were evaluated preoperatively and at 1 month postoperatively. Incision size changes were also evaluated. Results All surgeries were uneventful. Before intraocular lens implantation, the mean incision size was 2.24 ± 0.06 mm in both groups (P = 0.75). In terms of corneal endothelial cell density, neither preoperative (I vs II: 2304.1 ± 122.5 cell/mm2 vs 2315.6 ± 83.1 cell/mm2, P = 0.80) nor postoperative (I vs II: 2264.1 ± 124.3 cell/mm2 vs 2270.3 ± 89.9 cell/mm2, P = 0.98) differences between the groups were statistically significant. The mean endothelial cell density loss was 1.7% ± 1.6% and 2.0% ± 1.4% in groups I and II, respectively. Furthermore, no significant differences between groups I and II were found preoperatively (P = 0.40) and postoperatively (P = 0.68) in central pachymetry. With surgery, the mean increase in central pachymetry was 28.1 ± 23.6 μm and 24.0 ± 24.0 μm in groups I and II, respectively (P = 0.1). Conclusion Ellips™ FX transversal and OZil® IP torsional phacoemulsification modes are safe for performing cataract surgery, inducing minimal corneal

  7. Transient Receptor Potential Channels and Corneal Stromal Inflammation.

    PubMed

    Okada, Yuka; Reinach, Peter S; Shirai, Kumi; Kitano-Izutani, Ai; Miyajima, Masayasu; Yamanaka, Osamu; Sumioka, Takayoshi; Saika, Shizuya

    2015-11-01

    Corneal transparency is dependent on the maintenance of the structural integrity and functional activity of its epithelial and endothelial limiting layers and the stroma. Different transient receptor potential (TRP) channel subtypes are expressed in cells and on corneal sensory nerve endings. They serve as sensors and transducers of environmental stimuli that can reduce tissue transparency. These nonselective cation channels are members of a superfamily sharing TRP box protein sequence homology having 6 membrane spanning domains with a pore between the fifth and sixth segments. TRP channels are composed of 4 monomeric subunits that oligomerize in homomeric or heteromeric configurations derived from different TRP subtypes belonging to the same or any of 6 different subfamilies. TRP subfamily members identified in the cornea include those belonging to the canonical, vanilloid, ankyrin, or melastatin subfamilies. In this review, we specifically focus on the functional roles of TRPV1 and TRPA1 expression in the cornea as their activation provides adaptive nociceptive and immune responses to noxious environmental stresses such as irritating ligands, temperature fluctuations, rises in ambient osmolarity, mechanical stretch, decline in pH, and tissue injury. Our previous studies have indicated that TRPV1 and TRPA1 subtypes are potential drug targets for improving corneal wound healing after alkali burns, because injury-induced fibrosis, neovascularization, and inflammation in either TRPV1 or TRPA1 gene-silenced mice were all significantly reduced. PMID:26448171

  8. Effect of Stratification on Surface Properties of Corneal Epithelial Cells

    PubMed Central

    Yáñez-Soto, Bernardo; Leonard, Brian C.; Raghunathan, Vijay Krishna; Abbott, Nicholas L.; Murphy, Christopher J.

    2015-01-01

    Purpose The purpose of this study was to determine the influence of mucin expression in an immortalized human corneal epithelial cell line (hTCEpi) on the surface properties of cells, such as wettability, contact angle, and surface heterogeneity. Methods hTCEpi cells were cultured to confluence in serum-free medium. The medium was then replaced by stratification medium to induce mucin biosynthesis. The mucin expression profile was analyzed using quantitative PCR and Western blotting. Contact angles were measured using a two-immiscible liquid method, and contact angle hysteresis was evaluated by tilting the apparatus and recording advancing and receding contact angles. The spatial distribution of mucins was evaluated with fluorescently labeled lectin. Results hTCEpi cells expressed the three main ocular mucins (MUC1, MUC4, and MUC16) with a maximum between days 1 and 3 of the stratification process. Upon stratification, cells caused a very significant increase in contact angle hysteresis, suggesting the development of spatially discrete and heterogeneously distributed surface features, defined by topography and/or chemical functionality. Although atomic force microscopy measurements showed no formation of appreciable topographic features on the surface of the cells, we observed a significant increase in surface chemical heterogeneity. Conclusions The surface chemical heterogeneity of the corneal epithelium may influence the dynamic behavior of tear film by “pinning” the contact line between the cellular surface and aqueous tear film. Engineering the surface properties of corneal epithelium could potentially lead to novel treatments in dry eye disease. PMID:26747762

  9. [Influence of corneal transparency on the quality of topographies].

    PubMed

    Franko Zeitz, P; Kohlhaas, M

    2012-12-01

    Corneal topographs that measure the anterior and posterior corneal surface with optical methods need a clear cornea for precise measurements. Opacities cause artifacts in the corneal thickness (with measurements usually being too thin) and corneal curvatures. This is important to know as certain pathologies may repeatedly cause similar artifacts. This is highly relevant after a corneal cross-linking, Lasek or PRK, as these procedures cause typical artifacts that can easily be misinterpreted. PMID:23258670

  10. Terahertz sensing in corneal tissues

    PubMed Central

    Bennett, David B.; Taylor, Zachary D.; Tewari, Pria; Singh, Rahul S.; Culjat, Martin O.; Grundfest, Warren S.; Sassoon, Daniel J.; Johnson, R. Duncan; Hubschman, Jean-Pierre; Brown, Elliott R.

    2011-01-01

    This work introduces the potential application of terahertz (THz) sensing to the field of ophthalmology, where it is uniquely suited due to its nonionizing photon energy and high sensitivity to water content. Reflective THz imaging and spectrometry data are reported on ex-vivo porcine corneas prepared with uniform water concentrations using polyethylene glycol (PEG) solutions. At 79% water concentration by mass, the measured reflectivity of the cornea was 20.4%, 14.7%, 11.7%, 9.6%, and 7.4% at 0.2, 0.4, 0.6, 0.8, and 1 THz, respectively. Comparison of nine corneas hydrated from 79.1% to 91.5% concentration by mass demonstrated an approximately linear relationship between THz reflectivity and water concentration, with a monotonically decreasing slope as the frequency increases. The THz-corneal tissue interaction is simulated with a Bruggeman model with excellent agreement. THz applications to corneal dystrophy, graft rejection, and refractive surgery are examined from the context of these measurements. PMID:21639581

  11. Novel inhibitors of Anthrax edema factor

    PubMed Central

    Chen, Deliang; Misra, Milind; Sower, Laurie; Peterson, Johnny W.; Kellogg, Glen E.; Schein, Catherine H.

    2008-01-01

    Several pathogenic bacteria produce adenylyl cyclase toxins, such as the edema factor (EF) of Bacillus anthracis. These disturb cellular metabolism by catalyzing production of excessive amounts of the regulatory molecule cAMP. Here, a structure-based method, where a 3D- pharmacophore that fit the active site of EF was constructed from fragments, was used to identify non-nucleotide inhibitors of EF. A library of small molecule fragments was docked to the EF- active site in existing crystal structures and those with the highest HINT scores were assembled into a 3D-pharmacophore. About 10,000 compounds, from over 2.7 million compounds in the ZINC database, had a similar molecular framework. These were ranked according to their docking scores, using methodology that was shown to achieve maximum accuracy (i.e., how well the docked position matched the experimentally determined site for ATP analogues in crystal structures of the complex). Finally, 19 diverse compounds with the best AutoDock binding/docking scores were assayed in a cell based assay for their ability to reduce cAMP secretion induced by EF. Four of the test compounds, from different structural groups, inhibited in the low micromolar range. One of these has a core structure common to phosphatase inhibitors previously identified by high-throughput assays of a diversity library. Thus, the fragment based pharmacophore identified a small number of diverse compounds for assay, and greatly enhanced the selection process of advanced lead compounds for combinatorial design. PMID:18620864

  12. [Changes in epidural pulse pressure in brain edema following experimental focal ischemia].

    PubMed

    Mase, M

    1990-07-01

    It is well known that epidural pulse pressure (PP) increases with rising intracranial pressure (ICP). However, PP at the same ICP is not always identical in various intracranial pathologies. Many authors have investigated PP at increased states of ICP, but few studies related to brain edema have been done. This study was carried out in order to clarify the changes of PP in brain edema following focal ischemia. ICP and PP were measured in two groups of anesthetized dogs; 1) increased volume of CSF by cisternal saline injection (control, n = 5), 2) brain edema caused by focal ischemia (edema, n = 11). Ischemia was induced by electro-coagulation of the right anterior cerebral artery and by clipping the right middle cerebral artery and right internal carotid artery transorbitaly. The brain was recirculated for 6 hours after 2 hours of ischemia. The ischemic areas were identified by Evans blue, triphenyl tetrazolium chloride (TTC) or histological examination. Water content of the brain was measured by the wet-dry weight method. The canine focal ischemic model showed consistent ischemic damage in the caudate nucleus and produced brain edema successfully. PP increased linearly with rising ICP to 35 mmHg, and PP in the edema group was significantly smaller than that in the control group at the same ICP value. The slopes of the regression equation of ICP and PP were significantly different between the edema and control group (edema: 0.061 +/- 0.030, control: 0.107 +/- 0.015, mean +/- SD, p less than 0.01). These results suggest that PP is easily affected by ischemic brain edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2223260

  13. Response of corneal epithelial cells to Staphylococcus aureus

    PubMed Central

    2010-01-01

    Staphylococcus aureus is a leading cause of invasive infection. It also infects wet mucosal tissues including the cornea and conjunctiva. Conflicting evidence exists on the expression of Toll-like receptors by human corneal epithelial cells. It was therefore of interest to determine how epithelial cells from this immune privileged tissue respond to S. aureus. Further, it was of interest to determine whether cytolytic toxins, with the potential to cause ion flux or potentially permit effector molecule movement across the target cell membrane, alter the response. Microarrays were used to globally assess the response of human corneal epithelial cells to S. aureus. A large increase in abundance of transcripts encoding the antimicrobial dendritic cell chemokine, CCL20, was observed. CCL20 release into the medium was detected, and this response was found to be largely TLR2 and NOD2 independent. Corneal epithelial cells also respond to S. aureus by increasing the intracellular abundance of mRNA for inflammatory mediators, transcription factors, and genes related to MAP kinase pathways, in ways similar to other cell types. The corneal epithelial cell response was surprisingly unaffected by toxin exposure. Toxin exposure did, however, induce a stress response. Although model toxigenic and non-toxigenic strains of S. aureus were employed in the present study, the results obtained were strikingly similar to those reported for stimulation of vaginal epithelial cells by clinical toxic shock toxin expressing isolates, demonstrating that the initial epithelial cellular responses to S. aureus are largely independent of strain as well as epithelial cell tissue source. PMID:21178447

  14. Corneal Nerves in Health and Disease

    PubMed Central

    Shaheen, Brittany; Bakir, May; Jain, Sandeep

    2013-01-01

    Corneal nerves are responsible for the sensations of touch, pain, and temperature and play an important role in the blink reflex, wound healing, and tear production and secretion. Corneal nerve dysfunction is a frequent feature of diseases that cause opacities and result in corneal blindness. Corneal opacities rank as the second most frequent cause of blindness. Technological advances in in vivo corneal nerve imaging, such as optical coherence tomography and confocal scanning, have generated new knowledge regarding the phenomenological events that occur during reinnervation of the cornea following disease, injury, or surgery. The recent availability of transgenic neurofluorescent murine models has stimulated the search for molecular modulators of corneal nerve regeneration. New evidence suggests that neuro-regenerative and inflammatory pathways in the cornea are intertwined. Evidence-based treatment of neurotrophic corneal diseases includes using neuro-regenerative (blood component-based and neurotrophic factors), neuroprotective, and ensconcing (bandage contact lens and amniotic membrane) strategies and avoiding anti-inflammatory therapies, such as cyclosporine and corticosteroids. PMID:24461367

  15. Corneal nerves in health and disease.

    PubMed

    Shaheen, Brittany Simmons; Bakir, May; Jain, Sandeep

    2014-01-01

    Corneal nerves are responsible for the sensations of touch, pain, and temperature and play an important role in the blink reflex, wound healing, and tear production and secretion. Corneal nerve dysfunction is a frequent feature of diseases that cause opacities and result in corneal blindness. Corneal opacities rank as the second most frequent cause of blindness. Technological advances in in vivo corneal nerve imaging, such as optical coherence tomography and confocal scanning, have generated new knowledge regarding the phenomenological events that occur during reinnervation of the cornea following disease, injury, or surgery. The recent availability of transgenic neurofluorescent murine models has stimulated the search for molecular modulators of corneal nerve regeneration. New evidence suggests that neuroregenerative and inflammatory pathways in the cornea are intertwined. Evidence-based treatment of neurotrophic corneal diseases includes using neuroregenerative (blood component-based and neurotrophic factors), neuroprotective, and ensconcing (bandage contact lens and amniotic membrane) strategies and avoiding anti-inflammatory therapies, such as cyclosporine and corticosteroids. PMID:24461367

  16. Corneal laceration caused by river crab

    PubMed Central

    Vinuthinee, Naidu; Azreen-Redzal, Anuar; Juanarita, Jaafar; Zunaina, Embong

    2015-01-01

    A 5-year-old boy presented with right eye pain associated with tearing and photophobia of 1-day duration. He gave a history of playing with a river crab when suddenly the crab clamped his fingers. He attempted to fling the crab off, but the crab flew and hit his right eye. Ocular examination revealed a right eye corneal ulcer with clumps of fibrin located beneath the corneal ulcer and 1.6 mm level of hypopyon. At presentation, the Seidel test was negative, with a deep anterior chamber. Culture from the corneal scrapping specimen grew Citrobacter diversus and Proteus vulgaris, and the boy was treated with topical gentamicin and ceftazidime eyedrops. Fibrin clumps beneath the corneal ulcer subsequently dislodged, and revealed a full-thickness corneal laceration wound with a positive Seidel test and shallow anterior chamber. The patient underwent emergency corneal toileting and suturing. Postoperatively, he was treated with oral ciprofloxacin 250 mg 12-hourly for 1 week, topical gentamicin, ceftazidime, and dexamethasone eyedrops for 4 weeks. Right eye vision improved to 6/9 and 6/6 with pinhole at the 2-week follow-up following corneal suture removal. PMID:25678769

  17. Corneal laceration caused by river crab.

    PubMed

    Vinuthinee, Naidu; Azreen-Redzal, Anuar; Juanarita, Jaafar; Zunaina, Embong

    2015-01-01

    A 5-year-old boy presented with right eye pain associated with tearing and photophobia of 1-day duration. He gave a history of playing with a river crab when suddenly the crab clamped his fingers. He attempted to fling the crab off, but the crab flew and hit his right eye. Ocular examination revealed a right eye corneal ulcer with clumps of fibrin located beneath the corneal ulcer and 1.6 mm level of hypopyon. At presentation, the Seidel test was negative, with a deep anterior chamber. Culture from the corneal scrapping specimen grew Citrobacter diversus and Proteus vulgaris, and the boy was treated with topical gentamicin and ceftazidime eyedrops. Fibrin clumps beneath the corneal ulcer subsequently dislodged, and revealed a full-thickness corneal laceration wound with a positive Seidel test and shallow anterior chamber. The patient underwent emergency corneal toileting and suturing. Postoperatively, he was treated with oral ciprofloxacin 250 mg 12-hourly for 1 week, topical gentamicin, ceftazidime, and dexamethasone eyedrops for 4 weeks. Right eye vision improved to 6/9 and 6/6 with pinhole at the 2-week follow-up following corneal suture removal. PMID:25678769

  18. Surgical device for supporting corneal suturing

    NASA Astrophysics Data System (ADS)

    Ventura, Liliane; Oliveira, Gunter C. D.; De Groote, Jean-Jacques; Sousa, Sidney J. F.; Saia, Paula

    2009-02-01

    A system for ophthalmic surgery support has been developed in order to minimize the residual astigmatism due to the induced irregular shape of the cornea by corneal suture. The system projects 36 light spots, from LEDs, displayed in a precise circle at the lachrymal film of the examined cornea. The displacement, the size and deformation of the reflected image of these light spots are analyzed providing the keratometry and the circularity of the suture. Measurements in the range of 32D - 55D (up to 23D of astigmatism are possible to be obtained) and a self-calibration system has been designed in order to keep the system calibrated. Steel precision spheres have been submitted to the system and the results show 99% of correlation with the fabricant's nominal values. The system has been tested in 13 persons in order to evaluate its clinical applicability and has been compared to a commercial keratometer Topcon OM-4. The correlation factors are 0,92 for the astigmatism and 0.99 for the associated axis. The system indicates that the surgeon should achieve circularity >=98% in order to do not induce astigmatisms over 3D.

  19. Differences between real and predicted corneal shapes after aspherical corneal ablation.

    PubMed

    Anera, Rosario G; Villa, César; Jiménez, José R; Gutiérrez, Ramón; del Barco, Luis Jiménez

    2005-07-20

    We study the differences between real and expected corneal shapes, using an aspherical ablation algorithm with a known equation and avoiding the limitation imposed by most studies of refractive surgery in which the ablation equations are not known. We have calculated the theoretical corneal shape predicted by this algorithm, comparing this shape with the real corneal topography. The results indicate that the deviations that appear in the corneal shape are significant for visual performance and for the correction of eye aberrations. If we include in this analysis the effect of reflection losses and nonnormal incidence on the cornea, we can reduce corneal differences, but they will remain significant. These results confirm that it is essential to minimize corneal differences to achieve effective correction in refractive surgery. PMID:16047903

  20. Perspectives on edema in childhood nephrotic syndrome.

    PubMed

    Teoh, Chia Wei; Robinson, Lisa A; Noone, Damien

    2015-10-01

    There have been two major theories surrounding the development of edema in nephrotic syndrome (NS), namely, the under- and overfill hypotheses. Edema is one of the cardinal features of NS and remains one of the principal reasons for admission of children to the hospital. Recently, the discovery that proteases in the glomerular filtrate of patients with NS are activating the epithelial sodium channel (ENaC), resulting in intrarenal salt retention and thereby contributing to edema, might suggest that targeting ENaC with amiloride might be a suitable strategy to manage the edema of NS. Other potential agents, particularly urearetics and aquaretics, might also prove useful in NS. Recent evidence also suggests that there may be other areas involved in salt storage, especially the skin, and it will be intriguing to study the implications of this in NS. PMID:26290369

  1. Pedal edema associated with atypical antipsychotics

    PubMed Central

    Munshi, Santanu; Mukherjee, Shatavisa; Saha, Indranil; Sen, Sukanta

    2016-01-01

    This study describes a patient diagnosed as a case of bipolar affective disorder complaining of bothersome incidence of pedal edema 1 month after the initiation of atypical antipsychotic regimen with risperidone and quetiapine. All hematological and biochemical profiles were found to be normal. On discontinuation of risperidone, the condition remained unresolved even after 2 weeks, and the edema progressed reaching her calves. On tapering the dose of quetiapine, she started showing gradual improvement in edematous condition. Quetiapine was slowly discontinued. No further recurrence of edema occurred, and hence, no further medication changes were implemented. Pedal edema was found to be resolved within weeks of dechallenge of the regimen. Naranjo adverse drug reaction probability scale gave a score of 7 which denotes “probable” adverse drug reaction with quetiapine. PMID:26997731

  2. Distribution of Posterior Corneal Astigmatism According to Axis Orientation of Anterior Corneal Astigmatism

    PubMed Central

    Miyake, Toshiyuki; Shimizu, Kimiya; Kamiya, Kazutaka

    2015-01-01

    Purpose To investigate the distribution of posterior corneal astigmatism in eyes with with-the-rule (WTR) and against-the-rule (ATR) anterior corneal astigmatism. Methods We retrospectively examined six hundred eight eyes of 608 healthy subjects (275 men and 333 women; mean age ± standard deviation, 55.3 ± 20.2 years). The magnitude and axis orientation of anterior and posterior corneal astigmatism were determined with a rotating Scheimpflug system (Pentacam HR, Oculus) when we divided the subjects into WTR and ATR anterior corneal astigmatism groups. Results The mean magnitudes of anterior and posterior corneal astigmatism were 1.14 ± 0.76 diopters (D), and 0.37 ± 0.19 D, respectively. We found a significant correlation between the magnitudes of anterior and posterior corneal astigmatism (Pearson correlation coefficient r = 0.4739, P<0.001). In the WTR anterior astigmatism group, we found ATR astigmatism of the posterior corneal surface in 402 eyes (96.6%). In the ATR anterior astigmatism group, we found ATR posterior corneal astigmatism in 82 eyes (73.9%). Especially in eyes with ATR anterior corneal astigmatism of 1 D or more and 1.5 D or more, ATR posterior corneal astigmatism was found in 28 eyes (59.6%) and 9 eyes (42.9%), respectively. Conclusions WTR anterior astigmatism and ATR posterior astigmatism were found in approximately 68% and 91% of eyes, respectively. The magnitude and the axis orientation of posterior corneal astigmatism were not constant, especially in eyes having high ATR anterior corneal astigmatism, as is often the case in patients who have undergone toric IOL implantation. PMID:25625283

  3. Alloimmunity and Tolerance in Corneal Transplantation.

    PubMed

    Amouzegar, Afsaneh; Chauhan, Sunil K; Dana, Reza

    2016-05-15

    Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ∼90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression. In this review, we discuss the critical facets of corneal alloimmunity, including immune and angiogenic privilege, mechanisms of allosensitization, cellular and molecular mediators of graft rejection, and allotolerance induction. PMID:27183635

  4. Technology needs for corneal transplant surgery

    NASA Astrophysics Data System (ADS)

    Vaddavalli, Pravin K.; Yoo, Sonia H.

    2011-03-01

    Corneal transplant surgery has undergone numerous modifications over the years with improvements in technique, instrumentation and eye banking. The main goals of corneal transplantation are achieving excellent optical clarity with long-term graft survival. Penetrating, anterior and posterior lamellar surgery along with femtosecond laser technology have partially met these goals, but outcomes are often unpredictable and surgeon dependent. Technology to predictably separate stroma from Descemet's membrane, techniques to minimize endothelial cell loss, improvements in imaging technology and emerging techniques like laser welding that might replace suturing, eventually making corneal transplantation a refractively predictable procedure are on the wish list of the cornea surgeon.

  5. Enhancing effects of sericin on corneal wound healing in rat debrided corneal epithelium.

    PubMed

    Nagai, Noriaki; Murao, Takatoshi; Ito, Yoshimasa; Okamoto, Norio; Sasaki, Masahiro

    2009-05-01

    The protein sericin is the main constituent of silk. We demonstrate the effects of sericin on corneal wound healing in rat debrided corneal epithelium. We also determined the effects of sericin on cell adhesion and proliferation in a human cornea epithelial cell line (HCE-T). Epithelium was removed from the corneas of rats with a BD Micro-Sharp, and wounded corneas were dyed with a 1% fluorescein solution. The corneal wounds were monitored using a fundus camera TRC-50X equipped with a digital camera. The corneal wound of rats instilled with saline was approximately 10% healing at 12 h, and approximately 65% healing at 24 h after corneal epithelial abrasion. The corneal wounds of rats instilled with saline showed almost complete healing by 36 h after corneal epithelial abrasion. On the other hand, the corneal healing rate of rats instilled with sericin solution was higher than that of rats instilled with saline, and the corneal healing rate constant increased with increasing sericin concentration. In addition, the adhesion and proliferation of HCE-T cells treated with 0.01-0.5% sericin solutions were enhanced, reaching a maximum at treatments with 0.2 and 0.1% sericin solutions, respectively. The present study demonstrates that the instillation of sericin solution has a potent effect in promoting wound healing and wound-size reduction in rats, probably caused by increasing cell movement and proliferation. PMID:19420767

  6. The Relationship between Corvis ST Tonometry Measured Corneal Parameters and Intraocular Pressure, Corneal Thickness and Corneal Curvature

    PubMed Central

    Asaoka, Ryo; Nakakura, Shunsuke; Tabuchi, Hitoshi; Murata, Hiroshi; Nakao, Yoshitaka; Ihara, Noriko; Rimayanti, Ulfah; Aihara, Makoto; Kiuchi, Yoshiaki

    2015-01-01

    The purpose of the study was to investigate the correlation between Corneal Visualization Scheimpflug Technology (Corvis ST tonometry: CST) parameters and various other ocular parameters, including intraocular pressure (IOP) with Goldmann applanation tonometry. IOP with Goldmann applanation tonometry (IOP-G), central corneal thickness (CCT), axial length (AL), corneal curvature, and CST parameters were measured in 94 eyes of 94 normal subjects. The relationship between ten CST parameters against age, gender, IOP-G, AL, CST-determined CCT and average corneal curvature was investigated using linear modeling. In addition, the relationship between IOP-G versus CST-determined CCT, AL, and other CST parameters was also investigated using linear modeling. Linear modeling showed that the CST measurement ‘A time-1’ is dependent on IOP-G, age, AL, and average corneal curvature; ‘A length-1’ depends on age and average corneal curvature; ‘A velocity-1’ depends on IOP-G and AL; ‘A time-2’ depends on IOP-G, age, and AL; ‘A length-2’ depends on CCT; ‘A velocity-2’ depends on IOP-G, age, AL, CCT, and average corneal curvature; ‘peak distance’ depends on gender; ‘maximum deformation amplitude’ depends on IOP-G, age, and AL. In the optimal model for IOP-G, A time-1, A velocity-1, and highest concavity curvature, but not CCT, were selected as the most important explanatory variables. In conclusion, many CST parameters were not significantly related to CCT, but IOP usually was a significant predictor, suggesting that an adjustment should be made to improve their usefulness for clinical investigations. It was also suggested CST parameters were more influential for IOP-G than CCT and average corneal curvature. PMID:26485129

  7. Quantitative Assessment of UVA-Riboflavin Corneal Cross-Linking Using Nonlinear Optical Microscopy

    PubMed Central

    Chai, Dongyul; Gaster, Ronald N.; Roizenblatt, Roberto; Juhasz, Tibor; Brown, Donald J.

    2011-01-01

    Purpose. Corneal collagen cross-linking (CXL) by the use of riboflavin and ultraviolet-A light (UVA) is a promising and novel treatment for keratoconus and other ectatic disorders. Since CXL results in enhanced corneal stiffness, this study tested the hypothesis that CXL-induced stiffening would be proportional to the collagen autofluorescence intensity measured with nonlinear optical (NLO) microscopy. Methods. Rabbit eyes (n = 50) were separated into five groups including: (1) epithelium intact; (2) epithelium removed; (3) epithelium removed and soaked in riboflavin, (4) epithelium removed and soaked in riboflavin, with 15 minutes of UVA exposure; and (5) epithelium removed and soaked in riboflavin, with 30 minutes of UVA exposure. Corneal stiffness was quantified by measuring the force required to displace the cornea 500 μm. Corneas were then fixed in paraformaldehyde and sectioned, and the collagen autofluorescence over the 400- to 450-nm spectrum was recorded. Results. There was no significant difference in corneal stiffness among the three control groups. Corneal stiffness was significantly and dose dependently increased after UVA (P < 0.0005). Autofluorescence was detected only within the anterior stroma of the UVA-treated groups, with no significant difference in the depth of autofluorescence between different UVA exposure levels. The signal intensity was also significantly increased with longer UVA exposure (P < 0.001). Comparing corneal stiffness with autofluorescence intensity revealed a significant correlation between these values (R2 = 0.654; P < 0.0001). Conclusions. The results of this study indicate a significant correlation between corneal stiffening and the intensity of collagen autofluorescence after CXL. This finding suggests that the efficacy of CXL in patients could be monitored by assessing collagen autofluorescence. PMID:21508101

  8. Surgical compensation of presbyopia with corneal inlays.

    PubMed

    Konstantopoulos, Aris; Mehta, Jodhbir S

    2015-05-01

    Presbyopia, the physiological change in near vision that develops with ageing, gradually affects individuals older than 40 years and is a growing cause of visual disability due to ageing demographics of the global population. The routine use of computers and 'smartphones', combined with the affluence of the 'baby boomers' generation has set high standards for near vision correction. Corneal inlays are a relatively new treatment modality that is effective at compensating for presbyopia. The dimensions of these devices vary from 2 to 3.8 mm in diameter and 5 to 32 μm in thickness. They are implanted in the anterior corneal stroma of the non-dominant eye, most commonly, in a femtosecond laser created corneal pocket. They improve near vision by increasing the depth of focus, creating a hyper-prolate region of increased central cornea power or providing a refractive add power. This article reviews the literature on the efficacy and safety of corneal inlays. PMID:25652889

  9. Genetics Home Reference: congenital stromal corneal dystrophy

    MedlinePlus

    ... of decorin. This abnormal protein interferes with the organization of collagen fibrils in the cornea. As poorly arranged collagen fibrils accumulate, the cornea becomes cloudy. These corneal changes lead to reduced visual acuity and related eye ...

  10. Fuchs endothelial corneal dystrophy: current perspectives

    PubMed Central

    Vedana, Gustavo; Villarreal, Guadalupe; Jun, Albert S

    2016-01-01

    Fuchs endothelial corneal dystrophy (FECD) is the most common corneal dystrophy and frequently results in vision loss. Hallmarks of the disease include loss of corneal endothelial cells and formation of excrescences of Descemet’s membrane. Later stages involve all layers of the cornea. Impairment of endothelial barrier and pump function and cell death from oxidative and unfolded protein stress contribute to disease progression. The genetic basis of FECD includes numerous genes and chromosomal loci, although alterations in the transcription factor 4 gene are associated with the majority of cases. Definitive treatment of FECD is corneal transplantation. In this paper, we highlight advances that have been made in understanding FECD’s clinical features, pathophysiology, and genetics. We also discuss recent advances in endothelial keratoplasty and potential future treatments. PMID:26937169

  11. Corneal astigmatism change and wavefront aberration evaluation after cataract surgery: “Single” versus “paired opposite” clear corneal incisions

    PubMed Central

    Razmjoo, Hasan; Koosha, Nima; Vaezi, Mohammad Hadi; Rahimi, Behrooz; Peyman, Alireza

    2014-01-01

    Background: Correcting the pre-existing astigmatism is an optimal goal in cataract surgery. The aim of this study is to compare the astigmatic correcting effect of a single regular 3.2 mm clear corneal incision (CCI) with paired opposite CCI in cataract patients and effect of these incisions on optical aberrations using the wavefront quantitative analysis. Materials and Methods: This was a randomized controlled trial study undertaken in an ophthalmology referral center on 50 patients planned for cataract surgery who were randomized to either single 3.2 mm CCI or paired opposite CCI group. Post-operative evaluation was performed at 12 weeks and included refraction, keratometery, corneal topography and wavefront analysis. Corneal astigmatism and post-operative values were compared in two groups. Results: The mean pre-operative corneal astigmatism was 2.58 ± 1.03 D in the single incision group and 2.70 ± 0.94 D in the paired opposite incisions group. After 12 weeks of surgery, the corneal astigmatism was reached to 2.15 ± 0.82 D in single incision group and 1.63 ± 1.21 in the paired opposite incisions group. There was a statistically significant difference in two arms of treatment regarding to surgically induced astigmatism after 3 months. The mean post-operative total and higher order aberrations and values were not significantly different in two groups. Conclusion: The results of our study showed that paired opposite incisions is an effective procedure for reducing pre-existing corneal astigmatism in cataract surgery. Paired incisions did not show any beneficial effect regarding wavefront aberrations compared with conventional single incision method. PMID:25221766

  12. Collagen Cross-Linking Using Riboflavin and Ultraviolet-A for Corneal Thinning Disorders

    PubMed Central

    Pron, G; Ieraci, L; Kaulback, K

    2011-01-01

    reactions, there have been few reported complications. Those that have occurred tended to be related to side effects of the induced photochemical reactions and were generally reversible. However, to ensure that there are minimal complications with the use of CXL and irradiation, strict adherence to defined CXL procedural protocols is essential. Keywords Keratoconus, corneal cross-linking, corneal topography, corneal transplant, visual acuity, refractive error. PMID:23074417

  13. Corneal Biomechanics Determination in Healthy Myopic Subjects

    PubMed Central

    Qiu, Kunliang; Lu, Xuehui; Zhang, Riping; Wang, Geng

    2016-01-01

    Purpose. To determine the corneal biomechanical properties by using the Ocular Response Analyzer™ and to investigate potential factors associated with the corneal biomechanics in healthy myopic subjects. Methods. 135 eyes from 135 healthy myopic subjects were included in this cross-sectional observational study. Cornea hysteresis (CH), corneal resistance factor (CRF), cornea-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure (IOPg) were determined with the Reichert Ocular Response Analyzer (ORA). Univariate and multivariate regression analyses were performed to investigate factors associated with corneal biomechanics. Results. The mean CH and CRF were 9.82 ± 1.34 mmHg and 9.64 ± 1.57 mmHg, respectively. In univariate regression analysis, CH was significantly correlated with axial length, refraction, central corneal thickness (CCT), and IOPg (r = −0.27, 0.23, 0.45, and 0.21, resp.; all with p ≤ 0.015), but not with corneal curvature or age; CRF was significantly correlated with CCT and IOPg (r = 0.52 and 0.70, resp.; all with p < 0.001), but not with axial length/refraction, corneal curvature, or age. In multivariate regression analysis, axial length, IOPcc, and CCT were found to be independently associated with CH, while CCT and IOPg were associated with CRF. Conclusions. Both CH and CRF were positively correlated with CCT. Lower CH but not CRF was associated with increasing degree of myopia. Evaluation of corneal biomechanical properties should take CCT and myopic status into consideration. PMID:27525109

  14. Neutrophil Interactions with Keratocytes during Corneal Epithelial Wound Healing: A Role for CD18 Integrins

    PubMed Central

    Petrescu, Matei S.; Larry, Chonna L.; Bowden, Robert A.; Williams, George W.; Gagen, Debjani; Li, Zhijie; Smith, C. Wayne; Burns, Alan R.

    2007-01-01

    PURPOSE To determine the role of keratocytes and leukocyte β2 (CD18) integrins in neutrophil (PMN) migration through the corneal stroma after epithelial scrape injury. METHODS Using C57BL/6 wild-type and CD18−/− mice, corneas were excised at 6 hours (wild-type) or 24 hours (CD18−/−) after central corneal epithelial abrasion, time points determined previously to have similar levels of emigrated PMNs. Corneas were prepared for ultrastructural morphometric analysis of PMNs, keratocyte networks, and collagen. RESULTS Transmission electron microscopy revealed intact keratocyte networks within the paralimbus that were morphometrically similar, regardless of epithelial injury or mouse genotype. Secondary to epithelial abrasion, extravasated PMNs within the paralimbus developed close contacts with keratocytes and collagen. In wild-type mice, 40% of the PMN surface was in contact with the keratocyte surface, and this value decreased to 10% in CD18−/− mice. PMN contact with collagen was similar in wild-type and CD18−/− mice, with approximately 50% of the PMN surface contacting the collagen fibrils. Since corneal edema resulting from scrape injury was similar, regardless of genotype and did not involve structural changes in collagen fibrils, these data favor a direct role for CD18 in mediating PMN contact with keratocytes. CONCLUSIONS The data show that in response to epithelial scrape injury, PMN migration in the corneal stroma involves close contact between keratocytes and collagen. Although PMN-keratocyte contacts require CD18 integrins, contact with collagen is CD18 independent. Fundamentally, PMN migration along keratocyte networks constitutes the beginning of a new experimental concept for understanding leukocyte migration within the wounded cornea. PMID:17962453

  15. Role of phospholipase A₂ (PLA₂) inhibitors in attenuating apoptosis of the corneal epithelial cells and mitigation of Acanthamoeba keratitis.

    PubMed

    Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

    2013-08-01

    The aim of this study is to determine if the mannose-induced protein (MIP-133) from Acanthamoeba castellanii trophozoites induces apoptosis of corneal epithelial cells through a cytosolic phospholipase A2α (cPLA2α)-mediated pathway. The efficacy of cPLA2α inhibitors to provide protection against Acanthamoeba keratitis was examined in vivo. Chinese hamster corneal epithelial (HCORN) cells were incubated with or without MIP-133. MIP-133 induces significant increase in cPLA2α and macrophage inflammatory protein-2 (MIP-2/CXCL2) levels from corneal cells. Moreover, cPLA2α inhibitors, MAFP (Methyl-arachidonyl fluorophosphonate) and AACOCF3 (Arachidonyl trifluoromethyl ketone), significantly reduce cPLA2α and CXCL2 from these cells (P < 0.05). Additionally, cPLA2α inhibitors significantly inhibit MIP-133-induced apoptosis in HCORN cells (P < 0.05). Subconjunctival injection of purified MIP-133 in Chinese hamster eyes induced cytopathic effects resulting in corneal ulceration. Animals infected with A. castellanii-laden contact lenses and treated with AACOCF3 and CAY10650, showed significantly less severe keratitis as compared with control animals. Collectively, the results indicate that cPLA2α is involved in MIP-133 induced apoptosis of corneal epithelial cells, polymorphonuclear neutrophil infiltration, and production of CXCL2. Moreover, cPLA2α inhibitors can be used as a therapeutic target in Acanthamoeba keratitis. PMID:23792108

  16. The Effect of ABO Blood Incompatibility on Corneal Transplant Failure in Conditions with Low Risk of Graft Rejection

    PubMed Central

    Dunn, Steven P.; Stark, Walter J.; Doyle Stulting, R.; Lass, Jonathan H.; Sugar, Alan; Pavilack, Mark A.; Smith, Patricia W.; Tanner, Jean Paul; Dontchev, Mariya; Gal, Robin L.; Beck, Roy W.; Kollman, Craig; Mannis, Mark J.; Holland, Edward J.

    2009-01-01

    Purpose To determine whether corneal graft survival over a five-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs’ dystrophy or pseudophakic corneal edema, conditions at low risk for graft rejection. Design Multi-center prospective, double-masked, clinical trial Methods ABO blood group compatibility was determined for 1,002 donors and recipients. During a five-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were due to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects. Results ABO donor-recipient incompatibility was not associated with graft failure due to any cause including graft failure due to rejection, or with the occurrence of a rejection episode. The five-year cumulative incidence of graft failure due to rejection was 6% for recipients with ABO recipient-donor compatibility and 4% for those with ABO incompatibility (hazard ratio 0.65, 95% confidence interval 0.33 to 1.25, p=0.20). The five-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 12% for ABO compatible compared with 8% for ABO incompatible cases (p=0.09). Among clear grafts at five years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases. Conclusions In patients undergoing penetrating keratoplasty for Fuchs’ dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure due to graft rejection. PMID:19056078

  17. Diamond burr superficial keratectomy with mitomycin C for corneal scarring and high corneal astigmatism after pterygium excision

    PubMed Central

    Ozgurhan, Engin Bilge; Kara, Necip; Yildirim, Aydin; Alkin, Zeynep; Bozkurt, Ercument; Demirok, Ahmet

    2013-01-01

    Background The purpose of this paper is to report the successful treatment of corneal scarring and high corneal astigmatism secondary to previous pterygium surgery with diamond burr superficial keratectomy using mitomycin C. Methods Four patients with corneal scarring and high corneal astigmatism related to previous pterygium surgery underwent diamond burr superficial keratectomy with application of mitomycin C. Anterior segment photography and corneal topographic analysis were obtained preoperatively and postoperatively in all patients. Results Six months after surgery, corneal astigmatism and corneal aberrations were reduced in all patients. A clear cornea was achieved in all cases. No complications were noted during the follow-up period. Conclusion Diamond burr superficial keratectomy with application of mitomycin C is a potentially effective and simple procedure for treating patients with corneal scarring and high corneal astigmatism secondary to previous pterygium surgery. PMID:23737657

  18. Photothrombosis of Corneal Neovascularization by Photodynamic Therapy Utilizing Verteporfin and Diode Laser

    PubMed Central

    Ahmed Hassan, Aziza; Foad Ghoneim, Dina; Abdelraheem El-dib, Amr; Abdelkawi Ahmed, Salwa; Abdel- Salam, Ahmed Medhat

    2013-01-01

    Introduction: The aim of the present study was to evaluate the effect of photodynamic therapy in the treatment of experimental corneal neovascularization (NV) with benzoporphyrin derivative (BPD). Methods: One group was considered as control (n=6 eyes) then, corneal NV was induced in 30 New Zealand male rabbits (n=60 eyes) by placing 7.0 silk sutures at midstromal depth approximately1mm from the limbus. Fifteen rabbits with corneal NV were left without any treatment, and 15 rabbits were subjected to photodynamic therapy (PDT) by intravenous injection with Verteporfin at a dose of 1.5 mg /Kg. Diode laser (660 nm) was applied after 15 minutes for 5 minutes with a power of 50 mW/cm2. All rabbits were successively followed up by slit lamp examination for periods of 1 day, 1, 2, 3 and 4 weeks. Three rabbits were selected and sacrificed weekly (n=6 eyes each) and the corneas were isolated for histopathological examination. Results: The results of slit lamp examination indicated the gradual regression of the cornea neovascularization 4 weeks of PDT. Furthermore, regression of corneal neovascularization was documented clinically by decrease number and length of blood vessels and by histopathological examination. Conclusion: PDT with Verteporfin can provide efficacious treatment of corneal neovascularization. PMID:25606321

  19. The Effects of Silicone Hydrogel Lens Wear on the Corneal Epithelium and Risk for Microbial Keratitis

    PubMed Central

    Robertson, Danielle M.

    2012-01-01

    Previous studies using animal models and human clinical trials have demonstrated that the use of low oxygen transmissible contact lens materials produce corneal epithelial surface damage resulting in increased Pseudomonas aeruginosa (PA) adhesion and raft-mediated internalization into surface corneal epithelial cells. These findings led to the testable clinical predictions that: (1) microbial keratitis (MK) risk is expected to be greatest during the first 6 months of wear; (2) there is no difference between 6 and 30 night extended wear; and (3) that wear of hyper-oxygen transmissible lenses would reduce the reported incidence of infection. Subsequent epidemiological studies have confirmed the first two predictions; however, increased oxygen transmissibility with silicone hydrogel (SiHy) lens wear has not altered the overall incidence of MK. In this review, more recent clinical and basic studies that investigate epithelial alterations and bacterial adhesion to corneal epithelial cells following wear of SiHy lenses with and without concomitant exposure to chemically preserved multipurpose solutions (MPS) will be examined. The collective results of these studies demonstrate that even in the absence of lens-related hypoxia, MPS induce ocular surface changes during SiHy lens wear which are associated with a pathophysiological increase in PA adherence and internalization in the corneal epithelium, and therefore, predict an increased risk for PA-MK. In addition, new data supporting an interactive role for inflammation in facilitating PA adherence and internalization in the corneal epithelium will also be discussed. PMID:23266590

  20. Update on Pathologic Diagnosis of Corneal Infections and Inflammations

    PubMed Central

    Vemuganti, Geeta K.; Murthy, Somasheila I.; Das, Sujata

    2011-01-01

    One of the most frequent types of corneal specimen that we received in our pathology laboratory is an excised corneal tissue following keratoplasty. Several of these cases are due to corneal infections or the sequelae, like corneal scar. Advances in the histological and molecular diagnosis of corneal infections and inflammations have resulted in rapid and accurate diagnosis of the infectious agent and in the overall understanding of the mechanisms in inflammatory diseases of the cornea. This review provides an update of histopathological findings in various corneal infections and inflammations. PMID:22224015

  1. Isolated Bilateral Trigeminal Neuropathy in Sarcoidosis Presenting with Neurotrophic Corneal Ulcers

    PubMed Central

    Gupta, M.; Lascaratos, G.; Syrogiannis, A.; Esakowitz, L.

    2010-01-01

    Sarcoidosis is a multisystem granulomatous disease that may affect various organs. Nevertheless, involvement of the trigeminal nerve is exceedingly uncommon. This report presents a rare case of isolated bilateral trigeminal neuropathy presenting with neurotrophic corneal ulcers. The patient was treated with topical chloramphenicol and lubricants, as well as botulinum toxin injection to the upper eyelid to induce ptosis. Our case illustrates the importance of recognizing that bilateral corneal ulceration might be a manifestation of sarcoidosis. Physicians should be aware of this rare association, when treating sarcoidosis patients with eye related symptoms. PMID:23861615

  2. [Neurogenic pulmonary edema. Report of 2 cases].

    PubMed

    Dragosavac, D; Falcão, A L; Araújo, S; Terzi, R G

    1997-06-01

    Neurogenic pulmonary edema is a rare and serious complication in patients with head injury. It also may develop after a variety of cerebral insults such as subarachnoid hemorrhage, brain tumors and after epileptic seizures. Thirty six patients with severe head injury and four patients with cerebrovascular insults treated in Intensive Care Unit of HC-UNICAMP from January to September 1995 were evaluated. In this period there were two patients with neurogenic pulmonary edema, one with head injury and other with intracerebral hemorrhage. Diagnosis was made by rapid onset of pulmonary edema, severe hypoxemia, decrease of pulmonary complacence and diffuse pulmonary infiltrations, without previous history of tracheal aspiration or any other risk factor for development of adult respiratory distress syndrome. In the first case, with severe head trauma, neurogenic pulmonary edema was diagnosed at admission one hour after trauma, associated with severe systemic inflammatory reaction, and good outcome in three days. The second case, with hemorrhagic vascular insult, developed neurogenic pulmonary edema the fourth day after drainage of intracerebral hematoma and died. PMID:9629392

  3. Mechanisms of Astrocyte-Mediated Cerebral Edema

    PubMed Central

    Stokum, Jesse A.; Kurland, David B.; Gerzanich, Volodymyr; Simard, J. Marc

    2014-01-01

    Cerebral edema formation stems from disruption of blood brain barrier (BBB) integrity and occurs after injury to the CNS. Due to the restrictive skull, relatively small increases in brain volume can translate into impaired tissue perfusion and brain herniation. In excess, cerebral edema can be gravely harmful. Astrocytes are key participants in cerebral edema by virtue of their relationship with the cerebral vasculature, their unique compliment of solute and water transport proteins, and their general role in brain volume homeostasis. Following the discovery of aquaporins, passive conduits of water flow, aquaporin 4 (AQP4) was identified as the predominant astrocyte water channel. Normally, AQP4 is highly enriched at perivascular endfeet, the outermost layer of the BBB, whereas after injury, AQP4 expression disseminates to the entire astrocytic plasmalemma, a phenomenon termed dysregulation. Arguably, the most important role of AQP4 is to rapidly neutralize osmotic gradients generated by ionic transporters. In pathological conditions, AQP4 is believed to be intimately involved in the formation and clearance of cerebral edema. In this review, we discuss aquaporin function and localization in the BBB during health and injury, and we examine post-injury ionic events that modulate AQP4- dependent edema formation. PMID:24996934

  4. IL-17 and VEGF are necessary for efficient corneal nerve regeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) yo T cells, neutrophils, and platelets in t...

  5. Platelet recruitment promotes keratocyte repopulation following corneal epithelial abrasion in the mouse

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Corneal abrasion not only damages the epithelium but also induces stromal keratocyte death at the site of injury. While a coordinated cascade of inflammatory cell recruitment facilitates epithelial restoration, it is unclear if this cascade is necessary for keratocyte recovery. Since platelet and ne...

  6. Corneal Biomechanical Properties in Different Ocular Conditions and New Measurement Techniques

    PubMed Central

    Garcia-Porta, Nery; Salgado-Borges, Jose; Parafita-Mato, Manuel; González-Méijome, Jose Manuel

    2014-01-01

    Several refractive and therapeutic treatments as well as several ocular or systemic diseases might induce changes in the mechanical resistance of the cornea. Furthermore, intraocular pressure measurement, one of the most used clinical tools, is also highly dependent on this characteristic. Corneal biomechanical properties can be measured now in the clinical setting with different instruments. In the present work, we review the potential role of the biomechanical properties of the cornea in different fields of ophthalmology and visual science in light of the definitions of the fundamental properties of matter and the results obtained from the different instruments available. The body of literature published so far provides an insight into how the corneal mechanical properties change in different sight-threatening ocular conditions and after different surgical procedures. The future in this field is very promising with several new technologies being applied to the analysis of the corneal biomechanical properties. PMID:24729900

  7. Corneal Epithelial Wound Healing Promoted by Verbascoside-Based Liposomal Eyedrops

    PubMed Central

    Ambrosone, Luigi; Guerra, Germano; Cinelli, Mariapia; Filippelli, Mariaelena; Mosca, Monica; Vizzarri, Francesco; Giorgio, Dario; Costagliola, Ciro

    2014-01-01

    Different liposomal formulations were prepared to identify those capable of forming eyedrops for corneal diseases. Liposomes with neutral or slightly positive surface charge interact very well with the cornea. Then these formulations were loaded with verbascoside to heal a burn of corneal epithelium induced by alkali. The cornea surface affected involved in wound was monitored as a function of time. Experimental results were modeled by balance equation between the rate of healing, due to the flow of phenylpropanoid, and growth of the wound. The results indicate a latency time of only three hours and furthermore the corneal epithelium heals in 48 hours. Thus, the topical administration of verbascoside appears to reduce the action time of cells, as verified by histochemical and immunofluorescence assays. PMID:25165705

  8. Brain edema in acute liver failure. Insight from experimental studies.

    PubMed

    Andres, T; Blei, M D; Judy, R; Cho, M D

    1990-07-01

    Brain edema is a leading cause of death in fulminant hepatic failure (FHP). Animal studies are needed to gain further insight into its pathogenesis. The authors describe and analyze the results of brain studies in two animal models of FHF, the rabbit with galactosamine induced hepatitis and the anhepatic model of liver desvascularization. A gravimetric technique is used to determine water content in brain samples as small as 10 mg in weight. Results showed that water content is increased and correlates with the severity of encephalopathy in both experimental models of encephalopathy. The possible pathogenic role of ammonia and octanoic acid are discussed. PMID:19256151

  9. Daytime edema levels with plus powered low and high water content hydrogel contact lenses.

    PubMed

    La Hood, D

    1991-11-01

    Eleven unadapted contact lens wearers wore a high (74%) water content hydrogel lens (Permaflex, CooperVision) of oxygen transmissibility Dk/Lav 14 x 10(-9) in one eye and a low (43%) water content hydrogel lens (Aquaflex Superthin) of Dk/Lav 4 x 10(-9) in the other eye under open-eye conditions for 8 h. After 8 h, average corneal edema for the lower water content lens was 7.9 +/- 2.6%, which was significantly more than that for the higher water content lens, 1.7 +/- 1.6%. Significantly fewer corneal striae and folds were also seen in the eyes wearing the higher water content lens. Subjective ratings of lens comfort were significantly better for the higher water content lens. Low water content positive power hydrogel lenses of the thicknesses used in this study place unacceptable hypoxic stress on the cornea and therefore should not be used for all-day wear. PMID:1766650

  10. Detecting thermal phase transitions in corneal stroma by fluorescence micro-imaging analysis

    NASA Astrophysics Data System (ADS)

    Matteini, P.; Rossi, F.; Ratto, F.; Bruno, I.; Nesi, P.; Pini, R.

    2008-02-01

    Thermal modifications induced in corneal stroma were investigated by the use of fluorescence microscopy. Freshly extracted porcine corneas were immersed for 5 minutes in a water bath at temperatures in the 35-90°C range and stored in formalin. The samples were then sliced in 200-μm-thick transversal sections and analyzed under a stereomicroscope to assess corneal shrinkage. Fluorescence images of the thermally treated corneal samples were acquired using a slow-scan cooled CCD camera, after staining the slices with Indocyanine Green (ICG) fluorescent dye which allowed to detect fluorescence signal from the whole tissue. All measurements were performed using an inverted epifluorescence microscope equipped with a mercury lamp. The thermally-induced modifications to the corneal specimens were evaluated by studying the grey level distribution in the fluorescence images. For each acquired image, Discrete Fourier Transform (DFT) and entropy analyses were performed. The spatial distribution of DFT absolute value indicated the spatial orientation of the lamellar planes, while entropy was used to study the image texture, correlated to the stromal structural transitions. As a result, it was possible to indicate a temperature threshold value (62°C) for high thermal damage, resulting in a disorganization of the lamellar planes and in full agreement with the measured temperature for corneal shrinkage onset. Analysis of the image entropy evidenced five strong modifications in stromal architecture at temperatures of ~45°C, 53°C, 57°C, 66°C, 75°C. The proposed procedure proved to be an effective micro-imaging method capable of detecting subtle changes in corneal tissue subjected to thermal treatment.

  11. Bioengineering Organized, Multilamellar Human Corneal Stromal Tissue by Growth Factor Supplementation on Highly Aligned Synthetic Substrates

    PubMed Central

    Wu, Jian; Du, Yiqin; Mann, Mary M.; Yang, Enzhi; Funderburgh, James L.

    2013-01-01

    Recapitulating the microstructure of the native human corneal stromal tissue is believed to be a key feature in successfully engineering the corneal tissue. The stratified multilayered collagen fibril lamellae with orthogonal orientation determine the robust biomechanical properties of this tissue, and the uniform collagen fibril size and interfibrillar spacing are critical to its optical transparency. The objective of this investigation was to develop a highly organized collagen-fibril construct secreted by human corneal stromal stem cells (hCSSCs) to mimic the human corneal stromal tissue. In culture on a highly aligned fibrous substrate made from poly(ester urethane) urea, the fibroblast growth factor-2 (FGF-2, 10 ng/mL) and transforming growth factor-beta 3 (TGF-β3, 0.1 ng/mL) impacted the organization and abundance of the secreted collagen fibril matrix. hCSSCs differentiated into keratocytes with significant upregulation of the typical gene markers, including KERA, B3GnT7, and CHST6. FGF-2 treatment stimulated hCSSCs to secrete collagen fibrils strongly aligned in a single direction, whereas TGF-β3 induced collagenous layers with orthogonal fibril orientation. The combination of FGF-2 and TGF-β3 induced multilayered lamellae with orthogonally oriented collagen fibrils, in a pattern mimicking the human corneal stromal tissue. The constructs were 60–70 μm thick and had an increased content of cornea-specific extracellular matrix components, including keratan sulfate, lumican, and keratocan. The approach of combining substrate cues with growth factor augmentation offers a new means to engineer well-organized, collagen-based constructs with an appropriate nanoscale structure for corneal repair and regeneration. PMID:23557404

  12. Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization

    PubMed Central

    Onder, Halil Ibrahim; Erdurmus, Mesut; Bucak, Yasin Yücel; Simavli, Hüseyin; Oktay, Murat; Kukner, Ahmet Sahap

    2014-01-01

    AIM To evaluate the inhibitory effects of regorafenib (BAY 73-4506), a multikinase inhibitor, on corneal neovascularization (NV). METHODS Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (n = 6) received 0.9% NaCl, Group 2 (n = 6) received dimethyl sulfoxide, Group 3 (n = 6) received regorafenib 1 mg/mL, Group 4 (n =6) received bevacizumab 5 mg/mL and Group 5 (n = 6) received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea's total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining. RESULTS A statistically significant difference in the percent area of corneal NV was found among the groups (P <0.001). Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (P >0.005). There was a statistically significant difference among the groups in apoptotic cell density (P = 0.002). The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (P <0.05). The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2. CONCLUSION Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats. PMID:24790861

  13. Diabetic macular edema: New promising therapies

    PubMed Central

    Shamsi, Hanan N Al; Masaud, Jluwi S; Ghazi, Nicola G

    2013-01-01

    The treatment of diabetic macular edema is rapidly evolving. The era of laser therapy is being quickly replaced by an era of pharmacotherapy. Several pharmacotherapies have been recently developed for the treatment of retinal vascular diseases such as diabetic macular edema. Several intravitreal injections or sustained delivery devices have undergone phase 3 testing while others are currently being evaluated. The results of clinical trials have shown the superiority of some of these agents to laser therapy. However, with the availability of several of these newer agents, it may be difficult to individualize treatment options especially those patients respond differently to various therapies. As such, more effort is still needed in order to determine the best treatment regimen for a given patient. In this article, we briefly summarize the major new therapeutic additions for the treatment of diabetic macular edema and allude to some future promising therapies. PMID:24379924

  14. Novel imaging techniques for diabetic macular edema.

    PubMed

    Lobo, C; Bernardes, R; Faria de Abreu, J R; Cunha-Vaz, J G

    1999-01-01

    Retinal edema should be defined as any increase of water of the retinal tissue resulting in an increase in its volume. It may be of cytotoxic or vasogenic origin. Development of vasogenic macular edema is dependent on a series of factors such as blood pressure, blood-retinal barrier permeability, retinal cell damage, retinal tissue osmotic pressure and retinal tissue compliance. Objective measurements of retinal thickness are now possible using the Retinal Thickness Analyser. Localised measurements of blood-retinal barrier permeability may also be obtained using the Retinal Leakage Analyser, a modified confocal scanning laser fluorometer, while obtaining simultaneously angiographic images of the choroid and retina. These new imaging techniques show that cytotoxic and vasogenic retinal edema may occur independently in the early stages of diabetic retinopathy. These findings offer new perspectives for designing novel therapeutic strategies. PMID:10896349

  15. Acute pulmonary edema caused by quinine.

    PubMed

    Everts, Richard J; Hayhurst, Michael D; Nona, Basim P

    2004-09-01

    A 57-year-old man who had been intermittently taking one 300-mg tablet of quinine sulfate orally for leg cramps experienced transient acute pulmonary edema and hypotension 30-40 minutes after ingestion on two consecutive occasions. He was not taking any concomitant drugs, and there was no alternative explanation for either event. Serial troponin T tests and electrocardiograms, obtained on admission to the hospital, followed by an outpatient echocardiogram and a coronary angiogram, were essentially normal. We compared this case with one previously published and nine previously unpublished reports of quinine-associated pulmonary edema and conclude that some cases of pulmonary edema or adult respiratory distress syndrome in patients with malaria may be caused by an adverse reaction to quinine. Although infrequent, clinicians should be aware of this potentially serious and costly adverse reaction. PMID:15460183

  16. Rhodiola crenulata Extract Alleviates Hypoxic Pulmonary Edema in Rats

    PubMed Central

    Li, Min-Hui; Shi, Li-Shian; Ho, Cheng-Wen

    2013-01-01

    Sudden exposure of nonacclimatized individuals to high altitude can easily lead to high altitude illnesses. High altitude pulmonary edema (HAPE) is the most lethal form of high altitude illness. The present study was designed to investigate the ability of Rhodiola crenulata extract (RCE), an herbal medicine traditionally used as an antiacute mountain sickness remedy, to attenuate hypoxia-induced pulmonary injury. Exposure of animals to hypobaric hypoxia led to a significant increase in pathological indicators for pulmonary edema, including the lung water content, disruption of the alveolar-capillary barrier, and protein-rich fluid in the lungs. In addition, hypobaric hypoxia also increased oxidative stress markers, including (ROS) production, (MDA) level, and (MPO) activity. Furthermore, overexpression of plasma (ET-1), (VEGF) in (BALF), and (HIF-1α) in lung tissue was also found. However, pretreatment with RCE relieved the HAPE findings by curtailing all of the hypoxia-induced lung injury parameters. These findings suggest that RCE confers effective protection for maintaining the integrity of the alveolar-capillary barrier by alleviating the elevated ET-1 and VEGF levels; it does so by reducing hypoxia-induced oxidative stress. Our results offer substantial evidence to support arguments in favor of traditional applications of Rhodiola crenulata for antihigh altitude illness. PMID:23710233

  17. Cultured corneal epithelia for ocular surface disease.

    PubMed Central

    Schwab, I R

    1999-01-01

    PURPOSE: To evaluate the potential efficacy for autologous and allogeneic expanded corneal epithelial cell transplants derived from harvested limbal corneal epithelial stem cells cultured in vitro for the management of ocular surface disease. METHODS: Human Subjects. Of the 19 human subjects included, 18 (20 procedures) underwent in vitro cultured corneal epithelial cell transplants using various carriers for the epithelial cells to determine the most efficacious approach. Sixteen patients (18 procedures on 17 eyes) received autologous transplants, and 2 patients (1 procedure each) received allogeneic sibling grafts. The presumed corneal epithelial stem cells from 1 patient did not grow in vitro. The carriers for the expanded corneal epithelial cells included corneal stroma, type 1 collagen (Vitrogen), soft contact lenses, collagen shields, and amniotic membrane for the autologous grafts and only amniotic membrane for the allogeneic sibling grafts. Histologic confirmation was reviewed on selected donor grafts. Amniotic membrane as carrier. Further studies were made to determine whether amniotic membrane might be the best carrier for the expanding corneal epithelial cells. Seventeen different combinations of tryspinization, sonication, scraping, and washing were studied to find the simplest, most effective method for removing the amniotic epithelium while still preserving the histologic appearance of the basement membrane of the amnion. Presumed corneal epithelial stem cells were harvested and expanded in vitro and applied to the amniotic membrane to create a composite graft. Thus, the composite graft consisted of the amniotic membrane from which the original epithelium had been removed without significant histologic damage to the basement membrane, and the expanded corneal epithelial stem cells, which had been applied to and had successfully adhered to the denuded amniotic membrane. Animal model. Twelve rabbits had the ocular surface of 1 eye damaged in a standard

  18. Dose calculation for permanent prostate implants incorporating spatially anisotropic linearly time-resolving edema

    SciTech Connect

    Monajemi, T. T.; Clements, Charles M.; Sloboda, Ron S.

    2011-04-15

    Purpose: The objectives of this study were (i) to develop a dose calculation method for permanent prostate implants that incorporates a clinically motivated model for edema and (ii) to illustrate the use of the method by calculating the preimplant dosimetry error for a reference configuration of {sup 125}I, {sup 103}Pd, and {sup 137}Cs seeds subject to edema-induced motions corresponding to a variety of model parameters. Methods: A model for spatially anisotropic edema that resolves linearly with time was developed based on serial magnetic resonance imaging measurements made previously at our center to characterize the edema for a group of n=40 prostate implant patients [R. S. Sloboda et al., ''Time course of prostatic edema post permanent seed implant determined by magnetic resonance imaging,'' Brachytherapy 9, 354-361 (2010)]. Model parameters consisted of edema magnitude, {Delta}, and period, T. The TG-43 dose calculation formalism for a point source was extended to incorporate the edema model, thus enabling calculation via numerical integration of the cumulative dose around an individual seed in the presence of edema. Using an even power piecewise-continuous polynomial representation for the radial dose function, the cumulative dose was also expressed in closed analytical form. Application of the method was illustrated by calculating the preimplant dosimetry error, RE{sub preplan}, in a 5x5x5 cm{sup 3} volume for {sup 125}I (Oncura 6711), {sup 103}Pd (Theragenics 200), and {sup 131}Cs (IsoRay CS-1) seeds arranged in the Radiological Physics Center test case 2 configuration for a range of edema relative magnitudes ({Delta}=[0.1,0.2,0.4,0.6,1.0]) and periods (T=[28,56,84] d). Results were compared to preimplant dosimetry errors calculated using a variation of the isotropic edema model developed by Chen et al. [''Dosimetric effects of edema in permanent prostate seed implants: A rigorous solution,'' Int. J. Radiat. Oncol., Biol., Phys. 47, 1405-1419 (2000

  19. Nonallergic Eyelid Edema After Botulinum Toxin Type A Injection: Case Report and Review of Literature.

    PubMed

    Chang, Yin-Shuo; Chang, Chang-Cheng; Shen, Jen-Hsiang; Chen, Yu-Tsung; Chan, Karen Kar-Wun

    2015-09-01

    Periocular botulinum toxin type A (BoNTA) injections are generally safe. Ptosis is the most common adverse effect, whereas eyelid edema is rarely reported. There is no consensus on the latter's incidence, clinical course, or treatment strategy. Here we managed a 59-year-old woman who received BoNTA injections to her forehead, glabella, and eye corner. At 3-day follow-up, she presented with painless, nonpruritic, bilateral periorbital edema, and erythema. Preliminary diagnosis was a local allergic reaction, and topical corticosteroid was administered, but upon lack of improvement, edema secondary to venous and lymphatic congestion was hypothesized, and she was advised to apply hot pads over her eyes, blink frequently, and massage the area. Her eyelid edema resolved 2 weeks later. At 4-month follow-up, the patient requested and received another course of BoNTA at half the dose. Frequent blinking was instructed, and the patient reported a satisfactory outcome with no adverse effects. In our literature review, incidence of BoNTA-induced eyelid edema was 1.4% and showed Asian tendency. Although rare, BoNTA-induced periorbital edema is self-limiting, and normally resolves in 2 to 4 weeks without medical treatment. Patients at risk for edema, including Asian ethnicity, dermatochalasis, and poor periocular muscle tone, are advised to receive injections at half the dosage. Examination of the function and tone of the orbicularis oculi and levator palpebrae superioris muscles before treatment is recommended, and application of hot pads over the eyes, frequent blinking in the morning, and self-massage of the affected area to increase venous return have demonstrated to improve outcome. PMID:26402825

  20. Predictability of Sirius dual-scanning corneal tomography in the measurement of corneal power after photorefractive surgery.

    PubMed

    Fouda, Sameh M; Al-Nashar, Haitham Y; Ibrahim, Basem M; Bor'i, Ashraf

    2016-02-01

    Determining an accurate central corneal power (K) measurement is crucial for calculating the intraocular lens power in patients who are undergoing cataract extraction. The ideal method for measuring K is to use a device that works independently of the refractive surgery information. The Scheimpflug camera system offers a promising means of measuring the true corneal power after keratorefractive surgery. In this study, we investigated the accuracy of this system in measuring central corneal power after photorefractive corneal surgery by comparing it to the theoretically derived central corneal power by history method. A total of 120 eyes of 65 (35 females and 30 males) patients were included in this study. The mean change of refraction at the spectacle plane was 3.75 D, whereas the mean change of refraction at the corneal plane was 3.37 D. Using the Sirius dual-scanning corneal tomography, the mean change in corneal power was 3.96 D. No significant differences were detected between the mean post-operative corneal power measured by the Sirius tomographer and the mean change in refraction at the corneal plane calculated clinically (P = 0.076) and the correlation was found to be high (0.913). This study suggests that Sirius dual-scanning corneal tomography offers high predictability when measuring the central 5 mm corneal power in patients who have had myopic corneal photorefractive surgery. PMID:25982158

  1. Ascorbic acid repletion: A possible therapy for diabetic macular edema?

    PubMed

    May, James M

    2016-05-01

    Macular edema poses a significant risk for visual loss in persons with diabetic retinopathy. It occurs when plasma constituents and fluid leak out of damaged retinal microvasculature in the area of the macula, causing loss of central vision. Apoptotic loss of pericytes surrounding capillaries is perhaps the earliest feature of diabetic vascular damage in the macula, which is also associated with dysfunction of the endothelium and loss of the otherwise very tight endothelial permeability barrier. Increased oxidative stress is a key feature of damage to both cell types, mediated by excess superoxide from glucose-induced increases in mitochondrial metabolism, as well as by activation of the receptor for advanced glycation end products (RAGE). The latter in turn activates multiple pathways, some of which lead to increased oxidative stress, such as those involving NF-ĸB, NADPH oxidase, and endothelial nitric oxide synthase. Such cellular oxidative stress is associated with low cellular and plasma ascorbic acid levels in many subjects with diabetes in poor glycemic control. Whether repletion of low ascorbate in retinal endothelium and pericytes might help to prevent diabetic macular edema is unknown. However, cell culture studies show that the vitamin prevents high-glucose and RAGE-induced apoptosis in both cell types, that it preserves nitric oxide generated by endothelial cells, and that it tightens the leaky endothelial permeability barrier. Although these findings need to be confirmed in pre-clinical animal studies, it is worth considering clinical trials to determine whether adequate ascorbate repletion is possible and whether it might help to delay or even reverse early diabetic macular edema. PMID:26898503

  2. Genetics Home Reference: lattice corneal dystrophy type I

    MedlinePlus

    ... lattice pattern. Affected individuals often have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another. Corneal erosions are very painful and can cause sensitivity to ...

  3. Genetics Home Reference: lattice corneal dystrophy type II

    MedlinePlus

    ... In addition, affected individuals can have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another. Corneal erosions are very painful and can cause sensitivity to ...

  4. Acute Corneal Hydrops 3 Years after Intra-corneal Ring Segments and Corneal Collagen Cross-linking

    PubMed Central

    Antonios, Rafic; Dirani, Ali; Fadlallah, Ali; Chelala, Elias; Hamadeh, Adib; Jarade, Elias

    2016-01-01

    This case report describes a 15-year-old male with allergic conjunctivitis and keratoconus, who underwent uneventful intra-corneal ring segment (ICRS) implantation and corneal collagen cross-linking (CXL) in the right eye. During the follow-up periods, the patient was noted to have several episodes of allergic conjunctivitis that were treated accordingly. At the 2 years postoperatively, he presented with another episode of allergic conjunctivitis and progression of keratoconus was suspected on topography. However, the patient was lost to follow-up, until he presented with acute hydrops at 3 years postoperatively. There are no reported cases of acute corneal hydrops in cross-linked corneas. We suspect the young age, allergic conjunctivitis and eye rubbing may be a risk factors associated with possible progression of keratoconus after CXL. Prolonged follow-up and aggressive control of the allergy might be necessary in similar cases. PMID:26957859

  5. Anti-Inflammatory Effects of 4-Methylcyclopentadecanone on Edema Models in Mice

    PubMed Central

    Ma, Yukui; Li, Yue; Li, Xiufeng; Wu, Yingliang

    2013-01-01

    The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE2 and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD50 value of 4-MCPC in rats is greater than 5000 mg/kg. The ED50 of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE2 and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE2 and MPO in inflamed paws. PMID:24351869

  6. Corneal Collagen Cross-Linking Outcomes: Review

    PubMed Central

    Jankov II, Mirko R; Jovanovic, Vesna; Delevic, Sladjana; Coskunseven, Efekan

    2011-01-01

    Keratoconus is a condition characterized by biomechanical instability of the cornea, presenting in a progressive, asymmetric and bilateral way. Corneal collagen cross-linking with riboflavin and UVA (CXL) is a new technique of corneal tissue strengthening that combines the use of riboflavin as a photo sensitizer and UVA irradiation. The studies showed that CXL was effective in halting the progression of keratoconus over a period of up to four years. The published studies also revealed a reduction of max K readings by more than 2 D, while the postoperative SEQ was reduced by an average of more than 1 D, and refractive cylinder decreased by about 1 D. No eyes lost any line of BCDVA. Moreover, there was no significant decrease in endothelial cell density. It was also found that CXL treatment was effective with reducing corneal and total wavefront aberrations. Corneal cross-linking has also led to an arrest and/or even a partial reversal of keratectasia in the treatment of iatrogenic ectasia after excimer laser ablation. A primary intervention such as CXL should be considered to potentially increase the biomechanical stability of the corneal tissue and postpone the need of lamellar or penetrating keratoplasty. PMID:21448301

  7. Corneal and conjunctival sensitivity in rosacea patients

    PubMed Central

    Örnek, Nurgül; Karabulut, Ayşe Anıl; Örnek, Kemal; Onaran, Zafer; Usta, Gülşah

    2015-01-01

    Purpose To assess corneal and conjunctival sensitivity in rosacea patients. Methods A total of 55 patients with rosacea and 37 control subjects participated in the study. Corneal and conjunctival sensitivity was determined by Cochet-Bonnet esthesiometer. Subjective symptoms of ocular dryness were evaluated using Ocular Surface Disease Index (OSDI). Schirmer’s I test (ST), tear breakup time (tBUT) and ocular surface staining with fluorescein were carried out to measure objective signs. Results The mean corneal and conjunctival sensitivity did not differ significantly between rosacea patients and c