Retinal Prosthetics, Optogenetics, and Chemical Photoswitches

PubMed Central

2015-01-01

Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream

Longitudinal visualization of vascular occlusion, reperfusion, and remodeling in a zebrafish model of retinal vascular leakage using OCT angiography

NASA Astrophysics Data System (ADS)

Spitz, Kathleen; Bozic, Ivan; Desai, Vineet; Rao, Gopikrishna M.; Pollock, Lana M.; Anand-Apte, Bela; Tao, Yuankai K.

2017-02-01

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are two of the leading causes of blindness and visual impairment in the world. Neovascularization results in severe vision loss in DR and AMD and, thus, there is an unmet need to identify mechanisms of pathogenesis and novel anti-angiogenic therapies. Zebrafish is a leading model organism for studying human disease pathogenesis, and the highly conserved drug activity between zebrafish and humans and their ability to readily absorb small molecules dissolved in water has benefited pharmaceutical discovery. Here, we use optical coherence tomography (OCT) and OCT angiography (OCT-A) to perform noninvasive, in vivo retinal imaging in a zebrafish model of vascular leakage. Zebrafish were treated with diethylaminobenzaldehyde (DEAB) to induce vascular leakage and imaged with OCT and OCT-A at six time points over two weeks: baseline one day before treatment and one, three, six, eight, and ten days post treatment. Longitudinal functional imaging showed significant vascular response immediately after DEAB treatment. Observed vascular changes included partial or complete vascular occlusion immediately after treatment and reperfusion during a two-week period. Increased vascular tortuosity several days post treatment indicated remodeling, and bifurcations and collateral vessel formation were also observed. In addition, significant treatment response variabilities were observed in the contralateral eye of the same animal. Anatomical and functional normalization was observed in most animals by ten days post treatment. These preliminary results motivate potential applications of OCT-A as a tool for studying pathogenesis and therapeutic screening in zebrafish models of retinal vascular disease.

Retinal Laminar Architecture in Human Retinitis Pigmentosa Caused by Rhodopsin Gene Mutations

PubMed Central

Aleman, Tomas S.; Cideciyan, Artur V.; Sumaroka, Alexander; Windsor, Elizabeth A. M.; Herrera, Waldo; White, D. Alan; Kaushal, Shalesh; Naidu, Anjani; Roman, Alejandro J.; Schwartz, Sharon B.; Stone, Edwin M.; Jacobson, Samuel G.

2008-01-01

Purpose. To determine the underlying retinal micropathology in subclasses of autosomal dominant retinitis pigmentosa (ADRP) caused by rhodopsin (RHO) mutations. Methods. Patients with RHO-ADRP (n = 17, ages 6–73 years), representing class A (R135W and P347L) and class B (P23H, T58R, and G106R) functional phenotypes, were studied with optical coherence tomography (OCT), and colocalized visual thresholds were determined by dark- and light-adapted chromatic perimetry. Autofluorescence imaging was performed with near-infrared light. Retinal histology in hT17M-rhodopsin mice was compared with the human results. Results. Class A patients had only cone-mediated vision. The outer nuclear layer (ONL) thinned with eccentricity and was not detectable within 3 to 4 mm of the fovea. Scotomatous extracentral retina showed loss of ONL, thickening of the inner retina, and demelanization of RPE. Class B patients had superior–inferior asymmetry in function and structure. The superior retina could have normal rod and cone vision, normal lamination (including ONL) and autofluorescence of the RPE melanin; laminopathy was found in the scotomas. With Fourier-domain-OCT, there was apparent inner nuclear layer (INL) thickening in regions with ONL thinning. Retinal regions without ONL had a thick hyporeflective layer that was continuous with the INL from neighboring regions with normal lamination. Transgenic mice had many of the laminar abnormalities found in patients. Conclusions. Retinal laminar abnormalities were present in both classes of RHO-ADRP and were related to the severity of colocalized vision loss. The results in human class B and the transgenic mice support the following disease sequence: ONL diminution with INL thickening; amalgamation of residual ONL with the thickened INL; and progressive retinal remodeling with eventual thinning. PMID:18385078

Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.

PubMed

Benedicto, Ignacio; Lehmann, Guillermo L; Ginsberg, Michael; Nolan, Daniel J; Bareja, Rohan; Elemento, Olivier; Salfati, Zelda; Alam, Nazia M; Prusky, Glen T; Llanos, Pierre; Rabbany, Sina Y; Maminishkis, Arvydas; Miller, Sheldon S; Rafii, Shahin; Rodriguez-Boulan, Enrique

2017-05-19

The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch's membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Transcriptome analyses show that expression of extracellular matrix-related genes changes dramatically over this period. Co-culture experiments support the existence of a novel regulatory pathway: ECs secrete factors that remodel RPE basement membrane, and integrin receptors sense these changes triggering Rho GTPase signals that modulate RPE tight junctions and enhance RPE barrier function. We anticipate our results will spawn a search for additional roles of choroid ECs in RPE physiology and disease.

Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors

PubMed Central

Benedicto, Ignacio; Lehmann, Guillermo L.; Ginsberg, Michael; Nolan, Daniel J.; Bareja, Rohan; Elemento, Olivier; Salfati, Zelda; Alam, Nazia M.; Prusky, Glen T.; Llanos, Pierre; Rabbany, Sina Y.; Maminishkis, Arvydas; Miller, Sheldon S.; Rafii, Shahin; Rodriguez-Boulan, Enrique

2017-01-01

The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch's membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Transcriptome analyses show that expression of extracellular matrix-related genes changes dramatically over this period. Co-culture experiments support the existence of a novel regulatory pathway: ECs secrete factors that remodel RPE basement membrane, and integrin receptors sense these changes triggering Rho GTPase signals that modulate RPE tight junctions and enhance RPE barrier function. We anticipate our results will spawn a search for additional roles of choroid ECs in RPE physiology and disease. PMID:28524846

Retinal Image Quality Assessment for Spaceflight-Induced Vision Impairment Study

NASA Technical Reports Server (NTRS)

Vu, Amanda Cadao; Raghunandan, Sneha; Vyas, Ruchi; Radhakrishnan, Krishnan; Taibbi, Giovanni; Vizzeri, Gianmarco; Grant, Maria; Chalam, Kakarla; Parsons-Wingerter, Patricia

2015-01-01

Long-term exposure to space microgravity poses significant risks for visual impairment. Evidence suggests such vision changes are linked to cephalad fluid shifts, prompting a need to directly quantify microgravity-induced retinal vascular changes. The quality of retinal images used for such vascular remodeling analysis, however, is dependent on imaging methodology. For our exploratory study, we hypothesized that retinal images captured using fluorescein imaging methodologies would be of higher quality in comparison to images captured without fluorescein. A semi-automated image quality assessment was developed using Vessel Generation Analysis (VESGEN) software and MATLAB® image analysis toolboxes. An analysis of ten images found that the fluorescein imaging modality provided a 36% increase in overall image quality (two-tailed p=0.089) in comparison to nonfluorescein imaging techniques.

JNK Controls the Onset of Mitosis in Planarian Stem Cells and Triggers Apoptotic Cell Death Required for Regeneration and Remodeling

PubMed Central

Almuedo-Castillo, María; Crespo, Xenia; Seebeck, Florian; Bartscherer, Kerstin; Salò, Emili; Adell, Teresa

2014-01-01

Regeneration of lost tissues depends on the precise interpretation of molecular signals that control and coordinate the onset of proliferation, cellular differentiation and cell death. However, the nature of those molecular signals and the mechanisms that integrate the cellular responses remain largely unknown. The planarian flatworm is a unique model in which regeneration and tissue renewal can be comprehensively studied in vivo. The presence of a population of adult pluripotent stem cells combined with the ability to decode signaling after wounding enable planarians to regenerate a complete, correctly proportioned animal within a few days after any kind of amputation, and to adapt their size to nutritional changes without compromising functionality. Here, we demonstrate that the stress-activated c-jun–NH2–kinase (JNK) links wound-induced apoptosis to the stem cell response during planarian regeneration. We show that JNK modulates the expression of wound-related genes, triggers apoptosis and attenuates the onset of mitosis in stem cells specifically after tissue loss. Furthermore, in pre-existing body regions, JNK activity is required to establish a positive balance between cell death and stem cell proliferation to enable tissue renewal, remodeling and the maintenance of proportionality. During homeostatic degrowth, JNK RNAi blocks apoptosis, resulting in impaired organ remodeling and rescaling. Our findings indicate that JNK-dependent apoptotic cell death is crucial to coordinate tissue renewal and remodeling required to regenerate and to maintain a correctly proportioned animal. Hence, JNK might act as a hub, translating wound signals into apoptotic cell death, controlled stem cell proliferation and differentiation, all of which are required to coordinate regeneration and tissue renewal. PMID:24922054

Mechanism by which Untwisting of Retinal Leads to Productive Bacteriorhodopsin Photocycle States

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

Wolter, Tino; Elstner, Marcus; Fischer, Stefan

2014-01-01

Relaxation of the twisted-retinal photoproduct state triggers proton-coupled reaction cycle in retinal proteins. A key open question is whether the retinal relaxation path is governed by the intrinsic torsional properties of the retinal or rather by the interactions of the retinal with protein and water groups, given the crowded protein environments in which the retinal resides. We address this question by performing systematic quantum mechanical/molecular mechanical molecular dynamics computations of retinal dynamics in bacteriorhodopsin at different temperatures, reaction path computations, and assessment of the vibrational fingerprints of the retinal molecule. Our results demonstrate a complex dependence of the retinal dynamicsmore » and preferred geometry on temperature. As the temperature increases, the retinal dihedral angle samples values largely determined by its internal conformational energy. The protein environment shapes the energetics of retinal relaxation and provides hydrogen-bonding partners that stabilize the retinal geometry.« less

Müller stem cell dependent retinal regeneration.

PubMed

Chohan, Annu; Singh, Usha; Kumar, Atul; Kaur, Jasbir

2017-01-01

Müller Stem cells to treat ocular diseases has triggered enthusiasm across all medical and scientific communities. Recent development in the field of stem cells has widened the prospects of applying cell based therapies to regenerate ocular tissues that have been irreversibly damaged by disease or injury. Ocular tissues such as the lens and the retina are now known to possess cell having remarkable regenerative abilities. Recent studies have shown that the Müller glia, a cell found in all vertebrate retinas, is the primary source of new neurons, and therefore are considered as the cellular basis for retinal regeneration in mammalian retinas. Here, we review the current status of retinal regeneration of the human eye by Müller stem cells. This review elucidates the current status of retinal regeneration by Müller stem cells, along with major retinal degenerative diseases where these stem cells play regenerative role in retinal repair and replacement. Copyright © 2016. Published by Elsevier B.V.

Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation.

PubMed

Bianchi, E; Ripandelli, G; Feher, J; Plateroti, A M; Plateroti, R; Kovacs, I; Plateroti, P; Taurone, S; Artico, M

2015-01-01

The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings.

Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis

PubMed Central

Castaldi, E.; Cicchini, G. M.; Cinelli, L.; Rizzo, S.; Morrone, M. C.

2016-01-01

Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI). After surgery, six out of seven retinitis pigmentosa (RP) blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD) activity in V1 and the lateral geniculate nucleus (LGN) was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation. PMID:27780207

LIM Kinase, a Newly Identified Regulator of Presynaptic Remodeling by Rod Photoreceptors After Injury

PubMed Central

Wang, Weiwei; Townes-Anderson, Ellen

2015-01-01

Purpose Rod photoreceptors retract their axon terminals and develop neuritic sprouts in response to retinal detachment and reattachment, respectively. This study examines the role of LIM kinase (LIMK), a component of RhoA and Rac pathways, in the presynaptic structural remodeling of rod photoreceptors. Methods Phosphorylated LIMK (p-LIMK), the active form of LIMK, was examined in salamander retina with Western blot and confocal microscopy. Axon length within the first 7 hours and process growth after 3 days of culture were assessed in isolated rod photoreceptors treated with inhibitors of upstream regulators ROCK and p21-activated kinase (Pak) (Y27632 and IPA-3) and a direct LIMK inhibitor (BMS-5). Porcine retinal explants were also treated with BMS-5 and analyzed 24 hours after detachment. Because Ca2+ influx contributes to axonal retraction, L-type channels were blocked in some experiments with nicardipine. Results Phosphorylated LIMK is present in rod terminals during retraction and in newly formed processes. Axonal retraction over 7 hours was significantly reduced by inhibition of LIMK or its regulators, ROCK and Pak. Process growth was reduced by LIMK or Pak inhibition especially at the basal (axon-bearing) region of the rod cells. Combining Ca2+ channel and LIMK inhibition had no additional effect on retraction but did further inhibit sprouting after 3 days. In detached porcine retina, LIMK inhibition reduced rod axonal retraction and improved retinal morphology. Conclusions Thus structural remodeling, in the form of either axonal retraction or neuritic growth, requires LIMK activity. LIM kinase inhibition may have therapeutic potential for reducing pathologic rod terminal plasticity after retinal injury. PMID:26658506

Long Noncoding RNA-GAS5: A Novel Regulator of Hypertension-Induced Vascular Remodeling.

PubMed

Wang, Yang-Ning-Zhi; Shan, Kun; Yao, Mu-Di; Yao, Jin; Wang, Jia-Jian; Li, Xiang; Liu, Ban; Zhang, Yang-Yang; Ji, Yong; Jiang, Qin; Yan, Biao

2016-09-01

Vascular remodeling is an important pathological feature of hypertension, leading to increased vascular resistance and reduced compliance. Endothelial cell (EC) and vascular smooth muscle cell (VSMC) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of EC and VSMC function. Herein, we determined whether long noncoding RNA-growth arrest-specific 5 (GAS5) is involved in hypertension-related vascular remodeling. We revealed that GAS5 knockdown aggravated hypertension-induced microvascular dysfunction as shown by increased retinal neovascularization and capillary leakage. GAS5 regulated the remodeling of arteries, including caudal arteries, carotid arteries, renal arteries, and thoracic arteries. GAS5 was mainly expressed in ECs and VSMCs, and its expression was significantly downregulated in hypertension. GAS5 knockdown affected endothelial activation, endothelial proliferation, VSMC phenotypic conversion, and EC-VSMC communication in vivo and in vitro. Mechanistically, GAS5 regulated EC and VSMC function through β-catenin signaling. This study identified GAS5 as a critical regulator in hypertension and demonstrated the potential of gene therapy and drug development for treating hypertension. © 2016 American Heart Association, Inc.

ADAPTIVE MECHANISMS CONTROLLING UTERINE SPIRAL ARTERY REMODELING DURING THE ESTABLISHMENT OF PREGNANCY

PubMed Central

Soares, Michael J.; Chakraborty, Damayanti; Kubota, Kaiyu; Renaud, Stephen J.; Rumi, M.A. Karim

2015-01-01

Implantation of the embryo into the uterus triggers the initiation of hemochorial placentation. The hemochorial placenta facilitates the acquisition of maternal resources required for embryo/fetal growth. Uterine spiral arteries form the nutrient supply line for the placenta and fetus. This vascular conduit undergoes gestation stage-specific remodeling directed by maternal natural killer cells and embryo-derived invasive trophoblast lineages. The placentation site, including remodeling of the uterine spiral arteries, is shaped by environmental challenges. In this review, we discuss the cellular participants controlling pregnancy-dependent uterine spiral artery remodeling and mechanisms responsible for their development and function. PMID:25023691

Perspectives on biomechanical growth and remodeling mechanisms in glaucoma⋆

PubMed Central

Grytz, Rafael; Girkin, Christopher A.; Libertiaux, Vincent; Downs, J. Crawford

2012-01-01

Glaucoma is a blinding diseases in which damage to the axons results in loss of retinal ganglion cells. Experimental evidence indicates that chronic intraocular pressure elevation initiates axonal insult at the level of the lamina cribrosa. The lamina cribrosa is a porous collagen structure through which the axons pass on their path from the retina to the brain. Recent experimental studies revealed the extensive structural changes of the lamina cribrosa and its surrounding tissues during the development and progression of glaucoma. In this perspective paper we review the experimental evidence for growth and remodeling mechanisms in glaucoma including adaptation of tissue anisotropy, tissue thickening/thinning, tissue elongation/shortening and tissue migration. We discuss the existing predictive computational approaches that try to elucidate the potential biomechanical basis of theses growth and remodeling mechanisms and highlight open questions, challenges, and avenues for further development. PMID:23109748

Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response

PubMed Central

Vandersmissen, Ine; Craps, Sander; Depypere, Maarten; Coppiello, Giulia; van Gastel, Nick; Maes, Frederik; Carmeliet, Geert; Schrooten, Jan; Jones, Elizabeth A.V.; Umans, Lieve; Devlieger, Roland; Koole, Michel; Gheysens, Olivier; Zwijsen, An; Aranguren, Xabier L.

2015-01-01

Collateral remodeling is critical for blood flow restoration in peripheral arterial disease and is triggered by increasing fluid shear stress in preexisting collateral arteries. So far, no arterial-specific mediators of this mechanotransduction response have been identified. We show that muscle segment homeobox 1 (MSX1) acts exclusively in collateral arterial endothelium to transduce the extrinsic shear stimulus into an arteriogenic remodeling response. MSX1 was specifically up-regulated in remodeling collateral arteries. MSX1 induction in collateral endothelial cells (ECs) was shear stress driven and downstream of canonical bone morphogenetic protein–SMAD signaling. Flow recovery and collateral remodeling were significantly blunted in EC-specific Msx1/2 knockout mice. Mechanistically, MSX1 linked the arterial shear stimulus to arteriogenic remodeling by activating the endothelial but not medial layer to a proinflammatory state because EC but not smooth muscle cellMsx1/2 knockout mice had reduced leukocyte recruitment to remodeling collateral arteries. This reduced leukocyte infiltration in EC Msx1/2 knockout mice originated from decreased levels of intercellular adhesion molecule 1 (ICAM1)/vascular cell adhesion molecule 1 (VCAM1), whose expression was also in vitro driven by promoter binding of MSX1. PMID:26391659

ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy.

PubMed

Rothschild, Pierre-Raphaël; Salah, Sawsen; Berdugo, Marianne; Gélizé, Emmanuelle; Delaunay, Kimberley; Naud, Marie-Christine; Klein, Christophe; Moulin, Alexandre; Savoldelli, Michèle; Bergin, Ciara; Jeanny, Jean-Claude; Jonet, Laurent; Arsenijevic, Yvan; Behar-Cohen, Francine; Crisanti, Patricia

2017-08-18

In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.

A Review: Proteomics in Retinal Artery Occlusion, Retinal Vein Occlusion, Diabetic Retinopathy and Acquired Macular Disorders.

PubMed

Cehofski, Lasse Jørgensen; Honoré, Bent; Vorum, Henrik

2017-04-28

Retinal artery occlusion (RAO), retinal vein occlusion (RVO), diabetic retinopathy (DR) and age-related macular degeneration (AMD) are frequent ocular diseases with potentially sight-threatening outcomes. In the present review we discuss major findings of proteomic studies of RAO, RVO, DR and AMD, including an overview of ocular proteome changes associated with anti-vascular endothelial growth factor (VEGF) treatments. Despite the severe outcomes of RAO, the proteome of the disease remains largely unstudied. There is also limited knowledge about the proteome of RVO, but proteomic studies suggest that RVO is associated with remodeling of the extracellular matrix and adhesion processes. Proteomic studies of DR have resulted in the identification of potential therapeutic targets such as carbonic anhydrase-I. Proliferative diabetic retinopathy is the most intensively studied stage of DR. Proteomic studies have established VEGF, pigment epithelium-derived factor (PEDF) and complement components as key factors associated with AMD. The aim of this review is to highlight the major milestones in proteomics in RAO, RVO, DR and AMD. Through large-scale protein analyses, proteomics is bringing new important insights into these complex pathological conditions.

The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration.

PubMed

Washington, Ilyas; Saad, Leonide

2016-01-01

One of the earliest events preceding several forms of retinal degeneration is the formation and accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and underlying Bruch's membrane (BM). Such degenerations include Stargardt disease, Best disease, forms of retinitis pigmentosa, and age-related macular degeneration (AMD). Since their discovery in the 1990's, dimers of vitamin A, have been postulated as chemical triggers driving retinal senescence and degeneration. There is evidence to suggest that the rate at which vitamin A dimerizes and the eye's response to the dimerization products may dictate the retina's lifespan. Here, we present outstanding questions, finding the answers to which may help to elucidate the role of vitamin A dimerization in retinal degeneration.

Plastic roles of pericytes in the blood-retinal barrier.

PubMed

Park, Do Young; Lee, Junyeop; Kim, Jaeryung; Kim, Kangsan; Hong, Seonpyo; Han, Sangyeul; Kubota, Yoshiaki; Augustin, Hellmut G; Ding, Lei; Kim, Jin Woo; Kim, Hail; He, Yulong; Adams, Ralf H; Koh, Gou Young

2017-05-16

The blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption. However, PDGF-B/PDGFRβ signalling is expendable for maintaining BRB integrity in adult mice. Although selective pericyte loss in stable adult retinal vessels surprisingly does not cause BRB disintegration, it sensitizes retinal vascular endothelial cells (ECs) to VEGF-A, leading to upregulation of angiopoietin-2 (Ang2) in ECs through FOXO1 activation and triggering a positive feedback that resembles the pathogenesis of DR. Accordingly, either blocking Ang2 or activating Tie2 greatly attenuates BRB breakdown, suggesting potential therapeutic approaches to reduce retinal damages upon DR progression.

A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis

PubMed Central

Cassat, James E.; Hammer, Neal D.; Campbell, J. Preston; Benson, Meredith A.; Perrien, Daniel S.; Mrak, Lara N.; Smeltzer, Mark S.; Torres, Victor J.; Skaar, Eric P.

2013-01-01

Summary Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection. Pathogen-induced bone destruction limits antimicrobial penetration to the infectious focus and compromises treatment of osteomyelitis. To investigate mechanisms of S. aureus-induced bone destruction, we developed a murine model of osteomyelitis. Micro-computed tomography of infected femurs revealed that S. aureus triggers profound alterations in bone turnover. The bacterial regulatory locus sae was found to be critical for osteomyelitis pathogenesis, as Sae-regulated factors promote pathologic bone remodeling and intraosseous bacterial survival. Exoproteome analyses revealed the Sae-regulated protease aureolysin as a major determinant of the S. aureus secretome and identified the phenol soluble modulins as aureolysin-degraded, osteolytic peptides that trigger osteoblast cell death and bone destruction. These studies establish a murine model for pathogen-induced bone remodeling, define Sae as critical for osteomyelitis pathogenesis, and identify protease-dependent exoproteome remodeling as a major determinant of the staphylococcal virulence repertoire. PMID:23768499

Osteopontin and fibronectin levels are decreased in vitreous of autoimmune uveitis and retinal expression of both proteins indicates ECM re-modeling.

PubMed

Deeg, Cornelia A; Eberhardt, Christina; Hofmaier, Florian; Amann, Barbara; Hauck, Stefanie M

2011-01-01

Autoimmune uveitis is an intraocular inflammation that arises through autoreactive T-cells attacking the inner eye, eventually leading to blindness. However, the contributing molecular pathomechanisms within the affected tissues remain as yet elusive. The extracellular matrix (ECM) is a highly dynamic structure that varies tremendously and influences the encompassing tissue. In order to assess ECM re-modeling in autoimmune uveitis, we investigated the expression of ECM molecules fibronectin and osteopontin in vitreous and retina samples. This was carried out in the only spontaneous animal model for human autoimmue uveitis, namely equine recurrent uveitis (ERU) that resembles the human disease in clinical as well as in immunopathological aspects. ERU is a naturally occurring autoimmune disease in horses that develops frequently and has already proved its value to study disease-related pathomechanisms. Western blot analysis of fibronectin and osteopontin in healthy and uveitic vitreous revealed significant reduction of both proteins in uveitis. Immunohistochemical expression of fibronectin in healthy retinas was restricted to the inner limiting membrane abutting vimentin positive Müller cell endfeet, while in uveitic sections, a disintegration of the ILM was observed changing the fibronectin expression to a dispersed pattern extending toward the vitreous. Retinal expression of osteopontin in control tissue was found in a characteristic Müller cell pattern illustrated by co-localization with vimentin. In uveitic retinas, the immunoreactivity of osteopontin in gliotic Müller cells was almost absent. The ability of Müller cells to express fibronectin and osteopontin was additionally shown by immunocytochemistry of primary cultured equine Müller cells and the equine Müller cell line eqMC-7. In conclusion, severe ECM re-modeling in autoimmune uveitis reported here, might affect the adhesive function of fibronectin and thus the anchoring of Müller cell endfeet to

Macrophage Metalloelastase (MMP-12) Deficiency Mitigates Retinal Inflammation and Pathological Angiogenesis in Ischemic Retinopathy

PubMed Central

Li, Jingming; Wang, Joshua J.; Peng, Qisheng; Chen, Chen; Humphrey, Mary Beth; Heinecke, Jay; Zhang, Sarah X.

2012-01-01

Pathological angiogenesis is a major cause of vision loss in ischemic and inflammatory retinal diseases. Recent evidence implicates macrophage metalloelastase (MMP-12), a macrophage-derived elastinolytic protease in inflammation, tissue remodeling and angiogenesis. However, little is known about the role of MMP-12 in retinal pathophysiology. The present study aims to explore the enzyme’s contributions to retinal angiogenesis in oxygen-induced retinopathy (OIR) using MMP-12 knockout (KO) mice. We find that MMP-12 expression was upregulated in OIR, accompanied by elevated macrophage infiltration and increased inflammatory markers. Compared to wildtype mice, MMP-12 KO mice had decreased levels of adhesion molecule and inflammatory cytokines and reduced vascular leakage in OIR. Concomitantly, these mice had markedly reduced macrophage content in the retina with impaired macrophage migratory capacity. Significantly, loss of MMP-12 attenuated retinal capillary dropout in early OIR and mitigated pathological retinal neovascularization (NV). Similar results were observed in the study using MMP408, a pharmacological inhibitor of MMP-12. Intriguingly, in contrast to reducing pathological angiogenesis, lack of MMP-12 accelerated revascularization of avascular retina in OIR. Taken together, we conclude that MMP-12 is a key regulator of macrophage infiltration and inflammation, contributing to retinal vascular dysfunction and pathological angiogenesis. PMID:23285156

Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

PubMed Central

Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

2015-01-01

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

Gene replacement therapy for retinal CNG channelopathies.

PubMed

Schön, Christian; Biel, Martin; Michalakis, Stylianos

2013-10-01

Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

Metabolic remodeling triggered by salivation and diabetes in major salivary glands.

PubMed

Nogueira, Fernando N; Carvalho, Rui A

2017-02-01

The metabolic profile of major salivary glands was evaluated by 13 C nuclear magnetic resonance isotopomer analysis ( 13 C NMR-IA) following the infusion of [U- 13 C]glucose in order to define the true metabolic character of submandibular (SM) and parotid (PA) glands at rest and during salivary stimulation, and to determine the metabolic remodeling driven by diabetes. In healthy conditions, the SM gland is characterized at rest by a glycolytic metabolic profile and extensive pyruvate cycling. On the contrary, the PA gland, although also dominated by glycolysis, also possesses significant Krebs' cycle activity and does not sustain extensive pyruvate cycling. Under stimulation, both glands increase their glycolytic and Krebs' cycle fluxes, but the metabolic coupling between the two pathways is further compromised to account for the much increased biosynthetic anaplerotic fluxes. In diabetes, the responsiveness of the PA gland to a salivary stimulus is seriously hindered, mostly as a result of the incapacity to burst glycolytic activity and also an inability to improve the Krebs' cycle flux to compensate. The Krebs' cycle activity in the SM gland is also consistently compromised, but the glycolytic flux in this gland is more resilient. This diabetes-induced metabolic remodeling in SM and PA salivary glands illustrates the metabolic need to sustain adequate saliva production, and identifies glycolytic and oxidative pathways as key players in the metabolic dynamism of salivary glands. Copyright © 2016 John Wiley & Sons, Ltd.

A Review: Proteomics in Retinal Artery Occlusion, Retinal Vein Occlusion, Diabetic Retinopathy and Acquired Macular Disorders

PubMed Central

Cehofski, Lasse Jørgensen; Honoré, Bent; Vorum, Henrik

2017-01-01

Retinal artery occlusion (RAO), retinal vein occlusion (RVO), diabetic retinopathy (DR) and age-related macular degeneration (AMD) are frequent ocular diseases with potentially sight-threatening outcomes. In the present review we discuss major findings of proteomic studies of RAO, RVO, DR and AMD, including an overview of ocular proteome changes associated with anti-vascular endothelial growth factor (VEGF) treatments. Despite the severe outcomes of RAO, the proteome of the disease remains largely unstudied. There is also limited knowledge about the proteome of RVO, but proteomic studies suggest that RVO is associated with remodeling of the extracellular matrix and adhesion processes. Proteomic studies of DR have resulted in the identification of potential therapeutic targets such as carbonic anhydrase-I. Proliferative diabetic retinopathy is the most intensively studied stage of DR. Proteomic studies have established VEGF, pigment epithelium-derived factor (PEDF) and complement components as key factors associated with AMD. The aim of this review is to highlight the major milestones in proteomics in RAO, RVO, DR and AMD. Through large-scale protein analyses, proteomics is bringing new important insights into these complex pathological conditions. PMID:28452939

Retinal compensatory changes after light damage in albino mice

PubMed Central

Montalbán-Soler, Luis; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Salinas-Navarro, Manuel; Galindo-Romero, Caridad; Bezerra de Sá, Fabrízio; García-Ayuso, Diego; Avilés-Trigueros, Marcelino; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

2012-01-01

Purpose To investigate the anatomic and functional changes triggered by light exposure in the albino mouse retina and compare them with those observed in the albino rat. Methods BALB/c albino mice were exposed to 3,000 lx of white light during 24 h and their retinas analyzed from 1 to 180 days after light exposure (ALE). Left pupil mydriasis was induced with topical atropine. Retinal function was analyzed by electroretinographic (ERG) recording. To assess retinal degeneration, hematoxylin and eosin staining, the TdT-mediated dUTP nick-end labeling (TUNEL) technique, and quantitative immunohistofluorescence for synaptophysin and protein kinase Cα (PKCα) were used in cross sections. Intravenous injection of horseradish peroxidase and Fluoro-Gold™ tracing were used in whole-mounted retinas to study the retinal vasculature and the retinal ganglion cell (RGC) population, respectively. Results Light exposure caused apoptotic photoreceptor death in the central retina. This death was more severe in the dorsal than in the ventral retina, sparing the periphery. Neither retinal vascular leakage nor retinal ganglion cell death was observed ALE. The electroretinographic a-wave was permanently impaired, while the b-wave decreased but recovered gradually by 180 days ALE. The scotopic threshold responses, associated with the inner retinal function, diminished at first but recovered completely by 14 days ALE. This functional recovery was concomitant with the upregulation of protein kinase Cα and synaptophysin. Similar results were obtained in both eyes, irrespective of mydriasis. Conclusions In albino mice, light exposure induces substantial retinal damage, but the surviving photoreceptors, together with compensatory morphological/molecular changes, allow an important restoration of the retinal function. PMID:22509098

Short-interfering RNAs Induce Retinal Degeneration via TLR3 and IRF3

PubMed Central

Kleinman, Mark E; Kaneko, Hiroki; Cho, Won Gil; Dridi, Sami; Fowler, Benjamin J; Blandford, Alexander D; Albuquerque, Romulo JC; Hirano, Yoshio; Terasaki, Hiroko; Kondo, Mineo; Fujita, Takashi; Ambati, Balamurali K; Tarallo, Valeria; Gelfand, Bradley D; Bogdanovich, Sasha; Baffi, Judit Z; Ambati, Jayakrishna

2012-01-01

The discovery of sequence-specific gene silencing by endogenous double-stranded RNAs (dsRNA) has propelled synthetic short-interfering RNAs (siRNAs) to the forefront of targeted pharmaceutical engineering. The first clinical trials utilized 21-nucleotide (nt) siRNAs for the treatment of neovascular age-related macular degeneration (AMD). Surprisingly, these compounds were not formulated for cell permeation, which is required for bona fide RNA interference (RNAi). We showed that these “naked” siRNAs suppress neovascularization in mice not via RNAi but via sequence-independent activation of cell surface Toll-like receptor-3 (TLR3). Here, we demonstrate that noninternalized siRNAs induce retinal degeneration in mice by activating surface TLR3 on retinal pigmented epithelial cells. Cholesterol conjugated siRNAs capable of cell permeation and triggering RNAi also induce the same phenotype. Retinal degeneration was not observed after treatment with siRNAs shorter than 21-nts. Other cytosolic dsRNA sensors are not critical to this response. TLR3 activation triggers caspase-3-mediated apoptotic death of the retinal pigment epithelium (RPE) via nuclear translocation of interferon regulatory factor-3. While this unexpected adverse effect of siRNAs has implications for future clinical trials, these findings also introduce a new preclinical model of geographic atrophy (GA), a late stage of dry AMD that causes blindness in millions worldwide. PMID:21988875

Inner Segment Remodeling and Mitochondrial Translocation in Cone Photoreceptors in Age-Related Macular Degeneration With Outer Retinal Tubulation.

PubMed

Litts, Katie M; Messinger, Jeffrey D; Freund, K Bailey; Zhang, Yuhua; Curcio, Christine A

2015-04-01

To quantify impressions of mitochondrial translocation in degenerating cones and to determine the nature of accumulated material in the subretinal space with apparent inner segment (IS)-like features by examining cone IS ultrastructure. Human donor eyes with advanced age-related macular degeneration (AMD) were screened for outer retinal tubulation (ORT) in macula-wide, high-resolution digital sections. Degenerating cones inside ORT (ORT cones) and outside ORT (non-ORT cones) from AMD eyes and unaffected cones in age-matched control eyes were imaged using transmission electron microscopy. The distances of mitochondria to the external limiting membrane (ELM), cone IS length, and cone IS width at the ELM were measured. Outer retinal tubulation and non-ORT cones lose outer segments (OS), followed by shortening of IS and mitochondria. In non-ORT cones, IS broaden. Outer retinal tubulation and non-ORT cone IS myoids become undetectable due to mitochondria redistribution toward the nucleus. Some ORT cones were found lacking IS and containing mitochondria in the outer fiber (between soma and ELM). Unlike long, thin IS mitochondria in control cones, ORT and non-ORT IS mitochondria are ovoid or reniform. Shed IS, some containing mitochondria, were found in the subretinal space. In AMD, macula cones exhibit loss of detectable myoid due to IS shortening in addition to OS loss, as described. Mitochondria shrink and translocate toward the nucleus. As reflectivity sources, translocating mitochondria may be detectable using in vivo imaging to monitor photoreceptor degeneration in retinal disorders. These results improve the knowledge basis for interpreting high-resolution clinical retinal imaging.

Retinal detachment and retinal holes in retinitis pigmentosa sine pigmento.

PubMed

Csaky, K; Olk, R J; Mahl, C F; Bloom, S M

1991-01-01

Retinal detachment and retinal holes in two family members with retinitis pigmentosa sine pigmento are reported. We believe these are the first such cases reported in the literature. We describe the presenting symptoms and management, including cryotherapy, scleral buckling procedure, and sulfur hexafluoride injection (SF6), resulting in stable visual acuity in one case and retinal reattachment and improved visual acuity in the other case.

Role of Connective Tissue Growth Factor in the Retinal Vasculature during Development and Ischemia

PubMed Central

Pi, Liya; Xia, Huiming; Liu, Jianwen; Shenoy, Anitha K.; Hauswirth, William W.; Scott, Edward W.

2011-01-01

Purpose. To investigate the function of connective tissue growth factor (CTGF), a matricellular protein of the CCN (Cyr61/CTGF/Nov) family, in retinal vasculature during development and ischemia. Methods. CTGF expression was determined using RT-PCR, immunohistochemistry, and transgenic mice carrying CTGF promoter-driven-GFP. CTGF antibody was intraocularly injected into neonates at postnatal day (P)2, and its effect on retinal angiogenesis was analyzed at P4. Transgenic animals expressing GFP regulated by the glial fibrillary acidic protein promoter were used for astrocyte visualization. Retinal vascular occlusion was introduced by rose Bengal and laser photocoagulation on chimeric mice that were reconstituted with GFP+ bone marrow cells. Vascular repair in response to VEGF-A and CTGF was analyzed. Results. A temporal increase in CTGF at both mRNA and protein levels was observed in the ganglion cell layer and inner nuclear layer during development. Endothelial cells and pericytes were identified as the main cellular sources of CTGF during retinal angiogenesis. CTGF stimulated the migration of astrocytes, retinal endothelial cells, and pericytes in vitro. Inhibition of CTGF by specific antibody affected vascular filopodial extension, growth of the superficial vascular plexus, and astrocyte remodeling. In adult mice, CTGF was prominently expressed in the perivascular cells of arteries. CTGF activated bone marrow-derived perivascular cells and promoted fibrovascular membrane formation in the laser-induced adult retinopathy model. Conclusions. CTGF is expressed in vascular beds and acts on multiple cell types. It is important for vessel growth during early retinal development and promotes the fibrovascular reaction in murine retinal ischemia after laser injury. PMID:21969300

Retinal oximetry in patients with ischaemic retinal diseases.

PubMed

Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob

2017-03-01

The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO 2 ) were associated with present as well as increasing levels of DR. Four of six studies also found increased retinal arterial oxygen saturation (raSatO 2 ) in patients with DR. In patients with central retinal vein occlusion (CRVO), all studies found that rvSatO 2 was reduced, but raSatO 2 remained unchanged. Branch retinal vein occlusion was not associated with changes in retinal oxygen saturation, but this was based on a single study. In conclusion, DR is associated with increased rvSatO 2 and might also be related to increased raSatO 2 . Central retinal vein occlusion (CRVO) is correlated with increased rvSatO 2 but unrelated to raSatO 2 . Prospective studies are needed to expand these findings. These would tell whether retinal oximetry could be a potential tool for screening or a biomarker of treatment outcome in patients with ischaemic retinal diseases. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Superficial retinal precipitates in patients with syphilitic retinitis.

PubMed

Fu, Evelyn X; Geraets, Ryan L; Dodds, Emilio M; Echandi, Laura V; Colombero, Daniel; McDonald, H Richard; Jumper, J Michael; Cunningham, Emmett T

2010-01-01

The purpose of this study was to describe the occurrence of superficial retinal precipitates in patients with syphilitic retinitis. This was a retrospective, observational case series of nine eyes of eight patients with syphilitic retinitis associated with superficial retinal precipitates. The clinical, photographic, angiographic, and laboratory records were reviewed. Characteristics and treatment response of these superficial retinal precipitates were observed. All patients were Caucasian men, including 5 men who have sex with men (62.5%) and 6 (75.0%) who were positive for human immunodeficiency virus. None of the patients were previously diagnosed with syphilis. All patients developed panuveitis and a distinctly diaphanous or ground-glass retinitis associated with creamy yellow superficial retinal precipitates. In 3 patients (37.5%), the retinitis had a distinctive wedge-shaped appearance. Five patients (62.5%) had associated retinal vasculitis, 3 (37.5%) had serous retinal detachment, 2 (22.2%) had intraretinal hemorrhage, and 2 (22.2%) had papillitis. Within 2 weeks of initiating intravenous penicillin treatment, 7 patients (87.5%) experienced visual recovery to >or= 20/40. All affected eyes showed rapid resolution of clinical signs with minimal alternations of the retinal pigment epithelium in areas of prior retinitis after completion of antibiotic therapy. Characteristic superficial retinal precipitates may occur over areas of syphilitic retinitis. Improved recognition of this highly suggestive clinical sign may aid in early diagnosis and treatment.

Retinal Structure in Cobalamin C Disease: Mechanistic and Therapeutic Implications.

PubMed

Aleman, Tomas S; Brodie, Frank; Garvin, Christopher; Gewaily, Dina Y; Ficicioglu, Can H; Mills, Monte D; Forbes, Brian J; Maguire, Albert M; Davidson, Stefanie L

2015-01-01

To describe the retinal structure in a patient with cobalamin C (cblC) disease. A 13-year-old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). The patient carried a homozygous (c.271dupA) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. At age 3 months he had a normal eye exam. A pigmentary maculopathy progressed to chorioretinal atrophy from 5-10 months. ERG at 7 months was normal. A nystagmus remained stable since the age of 2 years. At age 13, visual acuity was 20/250 (right eye) and 20/400 (left eye), with a +5.00 D correction, a level of vision maintained since first measurable at age 5 years. SD-OCT showed bilateral macular coloboma-like lesions; there was also a thickened surface layer with ganglion cell layer thinning. Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL) transitioned to regions with no discernible ONL with a delaminated, thickened, inner retina. A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma-like lesions suggest there may be an interference with retinal/foveal development in cblC, a mechanism of maculopathy that may be shared by other early onset retinal degenerations. Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration.

Evidence for immune cell involvement in decidual spiral arteriole remodeling in early human pregnancy.

PubMed

Smith, Samantha D; Dunk, Caroline E; Aplin, John D; Harris, Lynda K; Jones, Rebecca L

2009-05-01

Decidual artery remodeling is essential for a healthy pregnancy. This process involves loss of vascular smooth muscle cells and endothelium, which are replaced by endovascular trophoblasts (vEVTs) embedded in fibrinoid. Remodeling is impaired during pre-eclampsia, a disease of pregnancy that results in maternal and fetal mortality and morbidity. Early vascular changes occur in the absence of vEVTs, suggesting that another cell type is involved; evidence from animal models indicates that decidual leukocytes play a role. We hypothesized that leukocytes participate in remodeling through the triggering of apoptosis or extracellular matrix degradation. Decidua basalis samples (8 to 12 weeks gestation) were examined by immunohistochemistry to elucidate associations between leukocytes, vEVTs, and key remodeling events. Trophoblast-independent and -dependent phases of remodeling were identified. Based on a combination of morphological attributes, vessel profiles were classified into a putative temporal series of four stages. In early stages of remodeling, vascular smooth muscle cells showed dramatic disruption and disorganization before vEVT presence. Leukocytes (identified as uterine natural killer cells and macrophages) were apparent infiltrating vascular smooth muscle cells layers and were matrix metalloproteinase-7 and -9 immunopositive. A proportion of vascular smooth muscle cells and endothelial cells were terminal deoxynucleotidyl transferase dUTP nick-end labeling positive, suggesting remodeling involves apoptosis. We thus confirm that vascular remodeling occurs in distinct trophoblast-independent and -dependent stages and provide the first evidence of decidual leukocyte involvement in trophoblast-independent stages.

Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2016-08-01

Objective. The field of retinal prosthetics has made major progress over the last decade, restoring visual percepts to people suffering from retinitis pigmentosa. The stimulation pulses used by present implants are suprathreshold, meaning individual pulses are designed to activate the retina. In this paper we explore subthreshold pulse sequences as an alternate stimulation paradigm. Subthreshold pulses have the potential to address important open problems such as fading of visual percepts when patients are stimulated at moderate pulse repetition rates and the difficulty in preferentially stimulating different retinal pathways. Approach. As a first step in addressing these issues we used Gaussian white noise electrical stimulation combined with spike-triggered averaging to interrogate whether a subthreshold sequence of pulses can be used to activate the mouse retina. Main results. We demonstrate that the retinal network can integrate multiple subthreshold electrical stimuli under an experimental paradigm immediately relevant to retinal prostheses. Furthermore, these characteristic stimulus sequences varied in their shape and integration window length across the population of retinal ganglion cells. Significance. Because the subthreshold sequences activate the retina at stimulation rates that would typically induce strong fading (25 Hz), such retinal ‘tickling’ has the potential to minimize the fading problem. Furthermore, the diversity found across the cell population in characteristic pulse sequences suggests that these sequences could be used to selectively address the different retinal pathways (e.g. ON versus OFF). Both of these outcomes may significantly improve visual perception in retinal implant patients.

Retinal profile and structural differences between myopes and emmetropes

NASA Astrophysics Data System (ADS)

Clark, Christopher Anderson

Refractive development has been shown to be influenced by optical defocus in the eye and the interpretation of this signal appears to be localized in the retina. Optical defocus is not uniform across the retina and has been suggested as a potential cause of myopia development. Specifically hyperopic focus, i.e. focusing light behind the retina, may signal the eye to elongate, causing myopia. This non-uniform hyperopic signal appears to be due to the retinal shape. Ultimately, these signals are detected by the retina in an as yet undetermined manner. The purpose of this thesis is to examine the retinal profile using a novel method developed at Indiana University and then to examine retinal structural changes across the retina associated with myopia. Myopes exhibited more prolate retinas than hyperopes/emmetropes using the SD OCT. Using the SD OCT, this profile difference was detectable starting at 5 degrees from the fovea, which was closer than previously reported in the literature. These results agreed significantly with results found from peripheral refraction and peripheral axial length at 10 degrees. Overall, the total retina was thinner for myopes than hyperopes/emmetropes. It was also statistically significantly thinner for the Outer Nuclear Layer (ONL), Inner Nuclear Layer (INL) and Outer Plexiform Layer (OPL) but not for other retinal layers such as the Ganglion Layer. Thinning generally occurred outside of 5 degrees. The SD OCT method provided a nearly 10 fold increase in sensitivity which allowed for detection of profile changes closer to the fovea. The location of the retinal changes may be interesting as the layers that showed significant differences in thickness are also layers that contain cells believed to be associated with refractive development (amacrine, bipolar, and photoreceptor cells.) The reason for the retinal changes cannot be determined with this study, but possible theories include stretch due to axial elongation, neural remodeling due to

Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors

PubMed Central

Zhang, Rong-wei; Li, Xiao-quan; Kawakami, Koichi; Du, Jiu-lin

2016-01-01

Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum. Its initiation is triggered by the activation of and consequent glutamate release from BC ATs, and is mediated by the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) expressed at these ATs. Intercellular asymmetry of NMDAR expression at BC ATs enables the preferential initiation of waves at the temporal retina, where BC ATs express more NMDARs. Thus, our findings indicate that glutamatergic retinal waves are initiated by BCs through a presynaptic NMDA autoreceptor-dependent process. PMID:27586999

Retinitis Pigmentosa

MedlinePlus

... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... is available? What treatment is available? What is retinitis pigmentosa? Retinitis pigmentosa, also known as RP, refers to ...

dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation

PubMed Central

Correia, Andreia; Santos, Marília A.; Relvas, João B.; Pereira, Paulo S.

2017-01-01

In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved. In here, we show that decreased cellular fitness in retinal progenitors caused by reduced Drosophila Myc expression triggers non cell-autonomous activation of retinal glia proliferation and overmigration. Glia migration occurs beyond its normal limit near the boundary between differentiated photoreceptors and precursor cells, extending into the progenitor domain. This overmigration is stimulated by JNK activation (and the function of its target Mmp1), while proliferative responses are mediated by Dpp/TGF-β signalling activation. PMID:28267791

Longitudinal in vivo imaging of retinal gliosis in a diabetic mouse model.

PubMed

Kumar, Saravana; Zhuo, Lang

2010-10-01

In this study, we visualize and quantify retinal gliosis in vivo for monitoring early diabetic retinopathy (DR) in a transgenic mouse model. Onset of diabetes was triggered via intraperitoneal injection of streptozotocin (STZ) into transgenic F1 hybrid (FVB/N × C57BL/6J) mice expressing green fluorescent protein (GFP) under the control of glial fibrillary acidic protein (GFAP) promoter. Retinal glial cells are imaged once pre-STZ treatment followed by weekly post-STZ imaging for five weeks using a confocal scanning laser ophthalmoscope. Mice develop diabetes one week after STZ induction as confirmed from the high blood glucose levels (>13.9 mmol/L). A significant increase is observed in the GFAP-GFP transgene expression from astrocytic cell bodies and processes as early as week 5 for the STZ-treated mice. Retinal astrocytes also undergo hyperplasia progressively from week 0 to 5. This precedes any structural abnormalities to the retinal vasculature. Immunohistochemistry (IHC) on retinal sections as well as quantitative RT-PCR of endogenous and transgene GFAP mRNA supports our in vivo observation. Our in vivo data correlates with clinical reports with regards to retinal gliosis-related inflammatory response during early diabetic retinopathy. This opens up the possibility of using in vivo molecular imaging of retinal glial cells as a platform for monitoring the efficacy of anti-DR drug candidates which intervene at an early stage.

Observation of Human Retinal Remodeling in Octogenarians with a Resveratrol Based Nutritional Supplement

PubMed Central

Richer, Stuart; Stiles, William; Ulanski, Lawrence; Carroll, Donn; Podella, Carla

2013-01-01

Purpose: Rare spontaneous remissions from age-related macular degeneration (AMD) suggest the human retina has large regenerative capacity, even in advanced age. We present examples of robust improvement of retinal structure and function using an OTC oral resveratrol (RV) based nutritional supplement called Longevinex® or L/RV (circa 2004, Resveratrol Partners, LLC, Las Vegas, NV, USA). RV, a polyphenolic phytoalexin caloric-restriction mimic, induces hormesis at low doses with widespread beneficial effects on systemic health. RV alone inhibits neovascularization in the murine retina. Thus far, published evidence includes L/RV mitigation of experimentally induced murine cardiovascular reperfusion injury, amelioration of human atherosclerosis serum biomarkers in a human Japanese randomized placebo controlled trial, modulation of micro RNA 20b and 539 that control hypoxia-inducing-factor (HIF-1) and vascular endothelial growth factor (VEGF) genes in the murine heart (RV inhibited micro RNA20b 189-fold, L/RV 1366-fold). Little is known about the effects of L/RV on human ocular pathology. Methods: Absent FDA IRB approval, but with permission from our Chief of Staff and medical center IRB, L/RV is reserved for AMD patients, on a case-by-case compassionate care basis. Patients include those who progress on AREDS II type supplements, refuse intra-vitreal anti-VEGF injections or fail to respond to Lucentis®, Avastin® or Eylea®. Patients are clinically followed traditionally as well as with multi-spectral retinal imaging, visual acuity, contrast sensitivity, cone glare recovery and macular visual fields. Three cases are presented. Results: Observed dramatic short-term anti-VEGF type effect including anatomic restoration of retinal structure with a suggestion of improvement in choroidal blood flow by near IR multispectral imaging. The visual function improvement mirrors the effect seen anatomically. The effect is bilateral with the added benefit of better RPE function

Outer Retinal Tubulation in Degenerative Retinal Disorders

PubMed Central

Goldberg, Naomi R.; Greenberg, Jonathan P.; Laud, Ketan; Tsang, Stephen; Freund, K. Bailey

2013-01-01

Objective To demonstrate outer retinal tubulation (ORT) in various degenerative retinal disorders. Methods This was a retrospective review of the multimodal imaging of 29 eyes of 15 patients with various retinal dystrophies and inflammatory maculopathies manifesting ORT. The morphologic features of ORT and its evolution over time were analyzed using spectral-domain optical coherence tomography (SD-OCT) data. Results Outer retinal tubulation was identified as round or ovoid structures with hyper-reflective borders in pattern dystrophy (6 eyes), acute zonal occult outer retinopathy (5 eyes), retinitis pigmentosa (4 eyes), Stargardt disease (4 eyes), gyrate atrophy (2 eyes), choroideremia (2 eyes), and various other degenerative conditions. These structures appeared to develop from the invagination of photoreceptors at the junction of intact and atrophic outer retina. During follow-up, the number and distribution of ORT largely remained stable. As zones of atrophy enlarged, the frequency of ORT appeared to increase. The ORT structures were found in fewer than 10% of patients with retinitis pigmentosa, Stargardt, or pattern dystrophy. Conclusion Outer retinal tubulation is found in various degenerative retinal disorders that share in common damage to the outer retina and/or retinal pigment epithelium. The presence of ORT may be in an indicator of underlying disease stage and severity. PMID:23676993

In vitro chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction.

PubMed

Jannasch, Maren; Weigel, Tobias; Engelhardt, Lisa; Wiezoreck, Judith; Gaetzner, Sabine; Walles, Heike; Schmitz, Tobias; Hansmann, Jan

2017-01-01

Surgical implantation of a biomaterial triggers foreign-body-induced fibrous encapsulation. Two major mechanisms of this complex physiological process are (I) chemotaxis of fibroblasts from surrounding tissue to the implant region, followed by (II) tissue remodeling. As an alternative to animal studies, we here propose a process-aligned in vitro test platform to investigate the material dependency of fibroblast chemotaxis and tissue remodeling mediated by material-resident macrophages. Embedded in a biomimetic three-dimensional collagen hydrogel, chemotaxis of fibroblasts in the direction of macrophage-material-conditioned cell culture supernatant was analyzed by live cell imaging. A combination of statistical analysis with a complementary parameterized random walk model allowed quantitative and qualitative characterization of the cellular walk process. We thereby identified an increasing macrophage-mediated chemotactic potential ranking of biomaterials from glass over polytetrafluorethylene to titanium. To address long-term effects of bio-material-resident macrophages on fibroblasts in a three-dimensional microenvironment, we further studied tissue remodeling by applying macrophage-material-conditioned medium on fibrous in vitro tissue models. A high correlation of the in vitro tissue model to state of the art in vivo study data was found. Titanium exhibited a significantly lower tissue remodeling capacity compared to polytetrafluorethylene. With this approach, we identified a material dependency of both chemotaxis and tissue remodeling processes, strengthening knowledge on their specific contribution to the foreign body reaction.

Development and recovery of laser-induced retinal injury in rats

NASA Astrophysics Data System (ADS)

Belokopytov, Mark; Dubinsky, Galina; Belkin, Michael; Epstein, Yoram; Rosner, Mordechai

2005-04-01

Retinal photocoagulation lesions undergo primary and secondary degeneration followed by partial healing. This study follows the sequential changes in laser-induced retinal lesion over a time span of 60 days. Argon laser lesions were created in 36 pigmented rats. Sections of the retinal lesions were evaluated by light microscopy 1, 24, 48, 72 hours, and 20, and 60 days after the injury (six animals at each time point). The diameter of the lesion was equal to that of the laser spot 1h after irradiation and increased by 24h. It decreased later, slightly during the following 48h and significantly by 20 days. The destruction of photoreceptors was most severe after 24-48h. The nuclei in the outer-nuclear layer were pyknotic at the lesion site at 1h and disappeared later. Healing processes began 72h after the irradiation and was completed by 60 days. Filling-in by sliding of near nuclei was observed by the 60th day. Reversible changes were seen also in the retinal pigment epithelium (with formation of a plaque at 72h and its degradation later on) and in the choroid (disorganization of capillaries by 48h with later reorganization). Conclusions: The development of a laser-induced injury is gradual. The photoreceptors are damaged first and than the damage spreads to other layers of retina and to areas adjacent the primary injury site. The extension of the damage is later stopped and the adjacent tissues tend to fill the lesion and remodel the retina.

Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization.

PubMed

Ye, Xin; Wang, Yanshu; Cahill, Hugh; Yu, Minzhong; Badea, Tudor C; Smallwood, Philip M; Peachey, Neal S; Nathans, Jeremy

2009-10-16

Disorders of vascular structure and function play a central role in a wide variety of CNS diseases. Mutations in the Frizzled-4 (Fz4) receptor, Lrp5 coreceptor, or Norrin ligand cause retinal hypovascularization, but the mechanisms by which Norrin/Fz4/Lrp signaling controls vascular development have not been defined. Using mouse genetic and cell culture models, we show that loss of Fz4 signaling in endothelial cells causes defective vascular growth, which leads to chronic but reversible silencing of retinal neurons. Loss of Fz4 in all endothelial cells disrupts the blood brain barrier in the cerebellum, whereas excessive Fz4 signaling disrupts embryonic angiogenesis. Sox17, a transcription factor that is upregulated by Norrin/Fz4/Lrp signaling, plays a central role in inducing the angiogenic program controlled by Norrin/Fz4/Lrp. These experiments establish a cellular basis for retinal hypovascularization diseases due to insufficient Frizzled signaling, and they suggest a broader role for Frizzled signaling in vascular growth, remodeling, maintenance, and disease.

A hybrid discrete-continuum mathematical model of pattern prediction in the developing retinal vasculature.

PubMed

McDougall, S R; Watson, M G; Devlin, A H; Mitchell, C A; Chaplain, M A J

2012-10-01

Pathological angiogenesis has been extensively explored by the mathematical modelling community over the past few decades, specifically in the contexts of tumour-induced vascularisation and wound healing. However, there have been relatively few attempts to model angiogenesis associated with normal development, despite the availability of animal models with experimentally accessible and highly ordered vascular topologies: for example, growth and development of the vascular plexus layers in the murine retina. The current study aims to address this issue through the development of a hybrid discrete-continuum mathematical model of the developing retinal vasculature in neonatal mice that is closely coupled with an ongoing experimental programme. The model of the functional vasculature is informed by a range of morphological and molecular data obtained over a period of several days, from 6 days prior to birth to approximately 8 days after birth. The spatio-temporal formation of the superficial retinal vascular plexus (RVP) in wild-type mice occurs in a well-defined sequence. Prior to birth, astrocytes migrate from the optic nerve over the surface of the inner retina in response to a chemotactic gradient of PDGF-A, formed at an earlier stage by migrating retinal ganglion cells (RGCs). Astrocytes express a variety of chemotactic and haptotactic proteins, including VEGF and fibronectin (respectively), which subsequently induce endothelial cell sprouting and modulate growth of the RVP. The developing RVP is not an inert structure; however, the vascular bed adapts and remodels in response to a wide variety of metabolic and biomolecular stimuli. The main focus of this investigation is to understand how these interacting cellular, molecular, and metabolic cues regulate RVP growth and formation. In an earlier one-dimensional continuum model of astrocyte and endothelial migration, we showed that the measured frontal velocities of the two cell types could be accurately reproduced

Imaging denatured collagen strands in vivo and ex vivo via photo-triggered hybridization of caged collagen mimetic peptides.

PubMed

Li, Yang; Foss, Catherine A; Pomper, Martin G; Yu, S Michael

2014-01-31

Collagen is a major structural component of the extracellular matrix that supports tissue formation and maintenance. Although collagen remodeling is an integral part of normal tissue renewal, excessive amount of remodeling activity is involved in tumors, arthritis, and many other pathological conditions. During collagen remodeling, the triple helical structure of collagen molecules is disrupted by proteases in the extracellular environment. In addition, collagens present in many histological tissue samples are partially denatured by the fixation and preservation processes. Therefore, these denatured collagen strands can serve as effective targets for biological imaging. We previously developed a caged collagen mimetic peptide (CMP) that can be photo-triggered to hybridize with denatured collagen strands by forming triple helical structure, which is unique to collagens. The overall goals of this procedure are i) to image denatured collagen strands resulting from normal remodeling activities in vivo, and ii) to visualize collagens in ex vivo tissue sections using the photo-triggered caged CMPs. To achieve effective hybridization and successful in vivo and ex vivo imaging, fluorescently labeled caged CMPs are either photo-activated immediately before intravenous injection, or are directly activated on tissue sections. Normal skeletal collagen remolding in nude mice and collagens in prefixed mouse cornea tissue sections are imaged in this procedure. The imaging method based on the CMP-collagen hybridization technology presented here could lead to deeper understanding of the tissue remodeling process, as well as allow development of new diagnostics for diseases associated with high collagen remodeling activity.

Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling

NASA Technical Reports Server (NTRS)

Theriot, Corey A.; Zanello, Susana B.

2014-01-01

Preliminary data from a prior tissue-sharing experiment has suggested that early growth response protein-1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia- or inflammation-driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated-weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS-induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell-specific isolectin binding, coupled to Alexa-488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z-axis. This new confocal microscope has the added capability of dye separation using the Linear

mTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects.

PubMed

Goncharova, Elena A

2013-05-01

Mammalian target of rapamycin (mTOR) is a major regulator of cellular metabolism, proliferation, and survival that is implicated in various proliferative and metabolic diseases, including obesity, type 2 diabetes, hamartoma syndromes, and cancer. Emerging evidence suggests a potential critical role of mTOR signaling in pulmonary vascular remodeling. Remodeling of small pulmonary arteries due to increased proliferation, resistance to apoptosis, and altered metabolism of cells forming the pulmonary vascular wall is a key currently irreversible pathological feature of pulmonary hypertension, a progressive pulmonary vascular disorder with high morbidity and mortality. In addition to rare familial and idiopathic forms, pulmonary hypertension is also a life-threatening complication of several lung diseases associated with hypoxia. This review aims to summarize our current knowledge and recent advances in understanding the role of the mTOR pathway in pulmonary vascular remodeling, with a specific focus on the hypoxia component, a confirmed shared trigger of pulmonary hypertension in lung diseases. We also discuss the emerging role of mTOR as a promising therapeutic target and mTOR inhibitors as potential pharmacological approaches to treat pulmonary vascular remodeling in pulmonary hypertension.

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

PubMed

Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

2012-02-07

Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

PubMed

Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

2016-08-10

We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. 2016 BMJ Publishing Group Ltd.

Analysis by NASA's VESGEN Software of Retinal Blood Vessels Before and After 70-Day Bed Rest: A Retrospective Study

NASA Technical Reports Server (NTRS)

Raghunandan, Sneha; Vyas, Ruchi J.; Vizzeri, Gianmarco; Taibbi, Giovanni; Zanello, Susana B.; Ploutz-Snyder, Robert; Parsons-Wingerter, Patricia A.

2016-01-01

Significant risks for visual impairment associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema and cotton wool spots. We hypothesize that microgravity-induced fluid shifts result in pathological changes within the retinal blood vessels that precede development of visual and other ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASAs innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) head-down tilt in human subjects before and after 70 days of bed rest, and (2) U.S. crew members before and after ISS missions. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage, potentially reversible progression of the visually impairing and blinding disease, diabetic retinopathy.

Inflammatory pathways are central to posterior cerebrovascular artery remodelling prior to the onset of congenital hypertension.

PubMed

Walas, Dawid; Nowicki-Osuch, Karol; Alibhai, Dominic; von Linstow Roloff, Eva; Coghill, Jane; Waterfall, Christy; Paton, Julian Fr

2018-01-01

Cerebral artery hypoperfusion may provide the basis for linking ischemic stroke with hypertension. Brain hypoperfusion may induce hypertension that may serve as an auto-protective mechanism to prevent ischemic stroke. We hypothesised that hypertension is caused by remodelling of the cerebral arteries, which is triggered by inflammation. We used a congenital rat model of hypertension and examined age-related changes in gene expression of the cerebral arteries using RNA sequencing. Prior to hypertension, we found changes in signalling pathways associated with the immune system and fibrosis. Validation studies using second harmonics generation microscopy revealed upregulation of collagen type I and IV in both tunica externa and media. These changes in the extracellular matrix of cerebral arteries pre-empted hypertension accounting for their increased stiffness and resistance, both potentially conducive to stroke. These data indicate that inflammatory driven cerebral artery remodelling occurs prior to the onset of hypertension and may be a trigger elevating systemic blood pressure in genetically programmed hypertension.

Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells.

PubMed

Clevenger, Tracy N; Luna, Gabriel; Boctor, Daniel; Fisher, Steven K; Clegg, Dennis O

2016-01-01

One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation. Poly(ethylene)-glycol hydrogels containing an Arg-Gly-Asp attachment sequence and a matrix metalloprotease 3/10 cleavage site supported adipose stem cell survival and showed remodeling initiated by adipogenic differentiation. Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed an increased number and area of lacunae or holes after adipose stem cell differentiation. Image analysis of adipose stem cells in Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed larger Voronoi domains, while cell density remained unchanged. The differentiated adipocytes residing within these newly remodeled spaces express proteins and messenger RNAs indicative of adipocytic differentiation. These engineered scaffolds may provide niches for stem cell differentiation and could prove useful in soft tissue regeneration.

Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells

PubMed Central

Clevenger, Tracy N; Luna, Gabriel; Boctor, Daniel; Fisher, Steven K; Clegg, Dennis O

2016-01-01

One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation. Poly(ethylene)-glycol hydrogels containing an Arg–Gly–Asp attachment sequence and a matrix metalloprotease 3/10 cleavage site supported adipose stem cell survival and showed remodeling initiated by adipogenic differentiation. Arg–Gly–Asp–matrix metalloprotease 3/10 cleavage site hydrogels showed an increased number and area of lacunae or holes after adipose stem cell differentiation. Image analysis of adipose stem cells in Arg–Gly–Asp–matrix metalloprotease 3/10 cleavage site hydrogels showed larger Voronoi domains, while cell density remained unchanged. The differentiated adipocytes residing within these newly remodeled spaces express proteins and messenger RNAs indicative of adipocytic differentiation. These engineered scaffolds may provide niches for stem cell differentiation and could prove useful in soft tissue regeneration. PMID:27733898

Retinal Oximetry Discovers Novel Biomarkers in Retinal and Brain Diseases.

PubMed

Stefánsson, Einar; Olafsdottir, Olof Birna; Einarsdottir, Anna Bryndis; Eliasdottir, Thorunn Scheving; Eysteinsson, Thor; Vehmeijer, Wouter; Vandewalle, Evelien; Bek, Toke; Hardarson, Sveinn Hakon

2017-05-01

Biomarkers for several eye and brain diseases are reviewed, where retinal oximetry may help confirm diagnosis or measure severity of disease. These include diabetic retinopathy, central retinal vein occlusion (CRVO), retinitis pigmentosa, glaucoma, and Alzheimer's disease. Retinal oximetry is based on spectrophotometric fundus imaging and measures oxygen saturation in retinal arterioles and venules in a noninvasive, quick, safe manner. Retinal oximetry detects changes in oxygen metabolism, including those that result from ischemia or atrophy. In diabetic retinopathy, venous oxygen saturation increases and arteriovenous difference decreases. Both correlate with diabetic retinopathy severity as conventionally classified on fundus photographs. In CRVO, vein occlusion causes hypoxia, which is measured directly by retinal oximetry to confirm the diagnosis and measure severity. In both diseases, the change in oxygen levels is a consequence of disturbed blood flow with resulting tissue hypoxia and vascular endothelial growth factor (VEGF) production. In atrophic diseases, such as retinitis pigmentosa and glaucoma, retinal oxygen consumption is reduced and this is detected by retinal oximetry. Retinal oximetry correlates with visual field damage and retinal atrophy. It is an objective metabolic measure of the degree of retinal atrophy. Finally, the retina is part of the central nervous system tissue and reflects central nervous system diseases. In Alzheimer's disease, a change in retinal oxygen metabolism has been discovered. Retinal oximetry is a novel, noninvasive technology that opens the field of metabolic imaging of the retina. Biomarkers in metabolic, ischemic, and atrophic diseases of the retina and central nervous system have been discovered.

Retinal Vasculitis

PubMed Central

Rosenbaum, James T.; Sibley, Cailin H.; Lin, Phoebe

2016-01-01

Purpose of review Ophthalmologists and rheumatologists frequently miscommunicate in consulting on patients with retinal vasculitis. This report seeks to establish a common understanding of the term, retinal vasculitis, and to review recent papers on this diagnosis. Recent findings 1) The genetic basis of some rare forms of retinal vascular disease have recently been described. Identified genes include CAPN5, TREX1, and TNFAIP3; 2) Behçet’s disease is a systemic illness that is very commonly associated with occlusive retinal vasculitis; 3) retinal imaging including fluorescein angiography and other newer imaging modalities has proven crucial to the identification and characterization of retinal vasculitis and its complications; 4) although monoclonal antibodies to IL-17A or IL-1 beta failed in trials for Behçet’s disease, antibodies to TNF alpha, either infliximab or adalimumab, have demonstrated consistent benefit in managing this disease. Interferon treatment and B cell depletion therapy via rituximab may be beneficial in certain types of retinal vasculitis. Summary Retinal vasculitis is an important entity for rheumatologists to understand. Retinal vasculitis associated with Behçet’s disease responds to monoclonal antibodies that neutralize TNF, but the many other forms of non-infectious retinal vasculitis may require alternate therapeutic management. PMID:26945335

Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling

PubMed Central

Quinton, Lee J.; Mizgerd, Joseph P.

2015-01-01

Pneumonia is initiated by microbes in the lung, but physiological processes integrating responses across diverse cell types and organ systems dictate the outcome of respiratory infection. Resistance, or actions of the host to eradicate living microbes, in the lungs involves a combination of innate and adaptive immune responses triggered by air-space infection. Resilience, or the ability of the host tissues to withstand the physiologically damaging effects of microbial and immune activities, is equally complex, precisely regulated, and determinative. Both immune resistance and tissue resilience are dynamic and change throughout the lifetime, but we are only beginning to understand such remodeling and how it contributes to the incidence of severe pneumonias, which diminishes as childhood progresses and then increases again among the elderly. Here, we review the concepts of resistance, resilience, and remodeling as they apply to pneumonia, highlighting recent advances and current significant knowledge gaps. PMID:25148693

Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling.

PubMed

Moro, Cécile; Jouan, Marie-Gabrielle; Rakotovao, Andry; Toufektsian, Marie-Claire; Ormezzano, Olivier; Nagy, Norbert; Tosaki, Arpad; de Leiris, Joël; Boucher, François

2007-11-01

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.

Central retinal artery occlusion - rethinking retinal survival time.

PubMed

Tobalem, Stephan; Schutz, James S; Chronopoulos, Argyrios

2018-04-18

The critical time from onset of complete occlusion of the central retinal artery (CRA) to functionally significant inner retinal infarction represents a window of opportunity for treatment and also has medical-legal implications, particularly when central retinal artery occlusion (CRAO) complicates therapeutic interventions. Here, we review the evidence for time to infarction from complete CRAO and discuss the implications of our findings. A Medline search was performed using each of the terms "central retinal artery occlusion", "retinal infarction", "retinal ischemia", and "cherry red spot" from 1970 to the present including articles in French and German. All retrieved references as well as their reference lists were screened for relevance. An Internet search using these terms was also performed to look for additional references. We find that the experimental evidence showing that inner retinal infarction occurs after 90-240 min of total CRAO, which is the interval generally accepted in the medical literature and practice guidelines, is flawed in important ways. Moreover, the retinal ganglion cells, supplied by the CRA, are part of the central nervous system which undergoes infarction after non-perfusion of 12-15 min or less. Retinal infarction is most likely to occur after only 12-15 min of complete CRAO. This helps to explain why therapeutic maneuvers for CRAO are often ineffective. Nevertheless, many CRAOs are incomplete and may benefit from therapy after longer intervals. To try to avoid retinal infarcton from inadvertent ocular compression by a headrest during prone anesthesia, the eyes should be checked at intervals of less than 15'.

Multiple Independent Oscillatory Networks in the Degenerating Retina

PubMed Central

Euler, Thomas; Schubert, Timm

2015-01-01

During neuronal degenerative diseases, microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. This can be particularly well observed in the retina, where photoreceptor degeneration triggers rewiring of connections in the retina’s first synaptic layer (e.g., Strettoi et al., 2003; Haq et al., 2014), while the synaptic organization of inner retinal circuits appears to be little affected (O’Brien et al., 2014; Figures 1A,B). Remodeling of (outer) retinal circuits and diminishing light-driven activity due to the loss of functional photoreceptors lead to spontaneous activity that can be observed at different retinal levels (Figure 1C), including the retinal ganglion cells, which display rhythmic spiking activity in the degenerative retina (Margolis et al., 2008; Stasheff, 2008; Menzler and Zeck, 2011; Stasheff et al., 2011). Two networks have been suggested to drive the oscillatory activity in the degenerating retina: a network of remnant cone photoreceptors, rod bipolar cells (RBCs) and horizontal cells in the outer retina (Haq et al., 2014), and the AII amacrine cell-cone bipolar cell network in the inner retina (Borowska et al., 2011). Notably, spontaneous rhythmic activity in the inner retinal network can be triggered in the absence of synaptic remodeling in the outer retina, for example, in the healthy retina after photo-bleaching (Menzler et al., 2014). In addition, the two networks show remarkable differences in their dominant oscillation frequency range as well as in the types and numbers of involved cells (Menzler and Zeck, 2011; Haq et al., 2014). Taken together this suggests that the two networks are self-sustained and can be active independently from each other. However, it is not known if and how they modulate each other. In this mini review, we will discuss: (i) commonalities and differences between these two oscillatory networks as well as possible interaction pathways; (ii) how multiple self

Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation.

PubMed

Huang, Zijing; Zhou, Tian; Sun, Xiaowei; Zheng, Yingfeng; Cheng, Bing; Li, Mei; Liu, Xialin; He, Chang

2018-01-01

Inflammation has emerged to be a critical mechanism responsible for neural damage and neurodegenerative diseases. Microglia, the resident innate immune cells in retina, are implicated as principal components of the immunological insult to retinal neural cells. The involvement of microglia in retinal inflammation is complex and here we propose for the first time that necroptosis in microglia triggers neuroinflammation and exacerbates retinal neural damage and degeneration. We found microglia experienced receptor-interacting protein kinase 1 (RIP1)- and RIP3-dependent necroptosis not only in the retinal degenerative rd1 mice, but also in the acute retinal neural injury mice. The necroptotic microglia released various pro-inflammatory cytokines and chemokines, such as tumor necrosis factor-α and chemokine (C-C motif) ligand 2, which orchestrated the retinal inflammation. Importantly, necroptosis blockade using necrostatin-1 could suppress microglia-mediated inflammation, rescue retinal degeneration or prevent neural injury in vivo. Meanwhile, cultured microglia underwent RIP1/3-mediated necroptosis and the necroptotic microglia produced large amounts of pro-inflammatory cytokines in response to lipopolysaccharide or oxidative stress in vitro. Mechanically, TLR4 deficiency ameliorated microglia necroptosis with decreased expression levels of machinery molecules RIP1 and RIP3, and suppressed retinal inflammation, suggesting that TLR4 signaling was required in microglia necroptosis-mediated inflammation. Thus, we proposed that microglia experienced necroptosis through TLR4 activation, promoting an inflammatory response that serves to exacerbate considerable neural damage and degeneration. Necroptosis blockade therefore emerged as a novel therapeutic strategy for tempering microglia-mediated neuroinflammation and ameliorating neural injury and neurodegenerative diseases.

Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation

PubMed Central

Huang, Zijing; Zhou, Tian; Sun, Xiaowei; Zheng, Yingfeng; Cheng, Bing; Li, Mei; Liu, Xialin; He, Chang

2018-01-01

Inflammation has emerged to be a critical mechanism responsible for neural damage and neurodegenerative diseases. Microglia, the resident innate immune cells in retina, are implicated as principal components of the immunological insult to retinal neural cells. The involvement of microglia in retinal inflammation is complex and here we propose for the first time that necroptosis in microglia triggers neuroinflammation and exacerbates retinal neural damage and degeneration. We found microglia experienced receptor-interacting protein kinase 1 (RIP1)- and RIP3-dependent necroptosis not only in the retinal degenerative rd1 mice, but also in the acute retinal neural injury mice. The necroptotic microglia released various pro-inflammatory cytokines and chemokines, such as tumor necrosis factor-α and chemokine (C-C motif) ligand 2, which orchestrated the retinal inflammation. Importantly, necroptosis blockade using necrostatin-1 could suppress microglia-mediated inflammation, rescue retinal degeneration or prevent neural injury in vivo. Meanwhile, cultured microglia underwent RIP1/3-mediated necroptosis and the necroptotic microglia produced large amounts of pro-inflammatory cytokines in response to lipopolysaccharide or oxidative stress in vitro. Mechanically, TLR4 deficiency ameliorated microglia necroptosis with decreased expression levels of machinery molecules RIP1 and RIP3, and suppressed retinal inflammation, suggesting that TLR4 signaling was required in microglia necroptosis-mediated inflammation. Thus, we proposed that microglia experienced necroptosis through TLR4 activation, promoting an inflammatory response that serves to exacerbate considerable neural damage and degeneration. Necroptosis blockade therefore emerged as a novel therapeutic strategy for tempering microglia-mediated neuroinflammation and ameliorating neural injury and neurodegenerative diseases. PMID:28885615

The relationship between neurotrophic factors and CaMKII in the death and survival of retinal ganglion cells.

PubMed

Cooper, N G F; Laabich, A; Fan, W; Wang, X

2008-01-01

The scientific discourse relating to the causes and treatments for glaucoma are becoming reflective of the need to protect and preserve retinal neurons from degenerative changes, which result from the injurious environment associated with this disease. Knowledge, in particular, of the signal transduction pathways which affect death and survival of the retinal ganglion cells is critical to this discourse and to the development of a suitable neurotherapeutic strategy for this disease. The goal of this chapter is to review what is known of the chief suspects involved in initiating the cell death/survival pathways in these cells, and what still remains to be uncovered. The least controversial aspect of the subject relates to the potential role of neurotrophic factors in the protection of the retinal ganglion cells. On the other hand, the postulated triggers for signaling cell death in glaucoma remain controversial. Certainly, the restricted flow of neurotrophic factors has been cited as one possible trigger. However, the connections between glaucoma and other factors present in the retina, such as glutamate, long held to be a prospective culprit in retinal ganglion cell death are still being questioned. Whatever the outcome of this particular debate, it is clear that the downstream intersections between the cell death and survival pathways should provide important foci for future studies whose goal is to protect retinal neurons, situated as they are, in the stressful environment of a cell destroying disease. The evidence for CaMKII being one of these intersecting points is discussed.

Focal retinal phlebitis.

PubMed

Hoang, Quan V; Freund, K Bailey; Klancnik, James M; Sorenson, John A; Cunningham, Emmett T; Yannuzzi, Lawrence A

2012-01-01

To report three cases of solitary, focal retinal phlebitis. An observational case series. Three eyes in three patients were noted to have unilateral decreased vision, macular edema, and a focal retinal phlebitis, which was not at an arteriovenous crossing. All three patients developed a branch retinal vein occlusion at the site of inflammation. These patients had no other evidence of intraocular inflammation, including vitritis, retinitis, retinal vasculitis, or choroiditis, nor was there any systemic disorder associated with inflammation, infection, or coagulation identified. Focal retinal phlebitis appears to be an uncommon and unique entity that produces macular edema and ultimately branch retinal vein occlusion. In our patients, the focal phlebitis and venous occlusion did not occur at an arteriovenous crossing, which is the typical site for branch retinal venous occlusive disease. This suggests that our cases represent a distinct clinical entity, which starts with a focal abnormality in the wall of a retinal venule, resulting in surrounding exudation and, ultimately, ends with branch retinal vein occlusion.

Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma

PubMed Central

Pitha, Ian F.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary Ellen; Oglesby, Ericka N.; Berlinicke, Cynthia A.; Mitchell, Katherine L.; Kim, Jessica; Jefferys, Joan J.

2015-01-01

Purpose To determine if oral losartan treatment decreases the retinal ganglion cell (RGC) death caused by experimental intraocular pressure (IOP) elevation in mice. Methods We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry. Results Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13), while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p < 0.0001). The lower RGC loss with losartan was significantly less than the loss with spironolactone or enalapril (regression model p = 0.001; drug treatment group term p = 0.01). Both losartan and enalapril significantly lowered blood pressure (p< 0.001), but losartan was protective, while enalapril led to worse than water-treated RGC loss. RGC loss after crush injury was unaffected by losartan treatment (difference from control p = 0.9). Survival of RGC in cell culture was not prolonged by sartan treatment. Axonal transport blockade after 3 day IOP elevations was less in losartan-treated than in control glaucoma eyes (p = 0.007). Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP. Conclusions The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes

Retinal flavoprotein autofluorescence as a measure of retinal health.

PubMed

Elner, Susan G; Elner, Victor M; Field, Matthew G; Park, Seung; Heckenlively, John R; Petty, Howard R

2008-01-01

To establish that increased autofluorescence of mitochondrial flavoproteins, an indicator of mitochondrial oxidative stress, correlates with retinal cell dysfunction. Retinal flavoprotein autofluorescence (FA) was imaged in humans with a fundus camera modified with 467DF8-nm excitation and 535-nm emission filters and a back-illuminated, electron-multiplying, charge-coupled device camera interfaced with a computer equipped with customized image capture software. Multiple digital images, centered on the fovea, were obtained from each eye. Histograms of pixel intensities in grayscale units were analyzed for average intensity and average curve width. Adults with diabetes mellitus, age-related macular degeneration (ARMD), central serous retinopathy, and retinal dystrophies, as well as healthy control volunteers, were imaged. Monolayers of cultured human retinal pigment epithelial (HRPE) cells, HRPE cells exposed to sublethal doses of H2O2, and HRPE cells exposed to H2O2 in the presence of antioxidants were imaged for FA using fluorescent photomicroscopy. Control patients demonstrated low levels of retinal FA, which increased progressively with age. Diabetics without visible retinopathy demonstrated increased FA levels compared to control volunteers (P < .001). Diabetics with retinopathy demonstrated significantly higher FA values than those without retinopathy (P < .04). Patients with ARMD, central serous retinopathy, or retinal dystrophies also demonstrated significantly increased FA. Compared to control RPE cells, cells oxidatively stressed with H2O2 had significantly elevated FA (P < .05), which was prevented by antioxidants (P < .05). Retinal FA is significantly increased with age and diseases known to be mediated by oxidative stress. Retinal FA imaging may provide a novel, noninvasive method of assessing retinal health and retinal dysfunction prior to retinal cell death.

New aspects of vascular remodelling: the involvement of all vascular cell types.

PubMed

McGrath, John C; Deighan, Clare; Briones, Ana M; Shafaroudi, Majid Malekzadeh; McBride, Melissa; Adler, Jeremy; Arribas, Silvia M; Vila, Elisabet; Daly, Craig J

2005-07-01

Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

Protection of retinal function by sulforaphane following retinal ischemic injury.

PubMed

Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

2015-09-01

Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automated feature extraction for retinal vascular biometry in zebrafish using OCT angiography

NASA Astrophysics Data System (ADS)

Bozic, Ivan; Rao, Gopikrishna M.; Desai, Vineet; Tao, Yuankai K.

2017-02-01

Zebrafish have been identified as an ideal model for angiogenesis because of anatomical and functional similarities with other vertebrates. The scale and complexity of zebrafish assays are limited by the need to manually treat and serially screen animals, and recent technological advances have focused on automation and improving throughput. Here, we use optical coherence tomography (OCT) and OCT angiography (OCT-A) to perform noninvasive, in vivo imaging of retinal vasculature in zebrafish. OCT-A summed voxel projections were low pass filtered and skeletonized to create an en face vascular map prior to connectivity analysis. Vascular segmentation was referenced to the optic nerve head (ONH), which was identified by automatically segmenting the retinal pigment epithelium boundary on the OCT structural volume. The first vessel branch generation was identified as skeleton segments with branch points closest to the ONH, and subsequent generations were found iteratively by expanding the search space outwards from the ONH. Biometric parameters, including length, curvature, and branch angle of each vessel segment were calculated and grouped by branch generation. Despite manual handling and alignment of each animal over multiple time points, we observe distinct qualitative patterns that enable unique identification of each eye from individual animals. We believe this OCT-based retinal biometry method can be applied for automated animal identification and handling in high-throughput organism-level pharmacological assays and genetic screens. In addition, these extracted features may enable high-resolution quantification of longitudinal vascular changes as a method for studying zebrafish models of retinal neovascularization and vascular remodeling.

Rapid light-induced activation of retinal microglia in mice lacking Arrestin-1.

PubMed

Levine, Emily S; Zam, Azhar; Zhang, Pengfei; Pechko, Alina; Wang, Xinlei; FitzGerald, Paul; Pugh, Edward N; Zawadzki, Robert J; Burns, Marie E

2014-09-01

Microglia dynamically prune synaptic contacts during development, and digest waste that accumulates in degeneration and aging. In many neurodegenerative diseases, microglial activation and phagocytosis gradually increase over months or years, with poorly defined initial triggering events. Here, we describe rapid retinal microglial activation in response to physiological light levels in a mouse model of photoreceptor degeneration that arises from defective rhodopsin deactivation and prolonged signaling. Activation, migration and proliferation of microglia proceeded along a well-defined time course apparent within 12 h of light onset. Retinal imaging in vivo with optical coherence tomography revealed dramatic increases in light-scattering from photoreceptors prior to the outer nuclear layer thinning classically used as a measure of retinal neurodegeneration. This model is valuable for mechanistic studies of microglial activation in a well-defined and optically accessible neural circuit, and for the development of novel methods for detecting early signs of pending neurodegeneration in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

The protective effect of prophylactic ozone administration against retinal ischemia-reperfusion injury.

PubMed

Kal, Ali; Kal, Oznur; Akillioglu, Ishak; Celik, Esin; Yilmaz, Mustafa; Gonul, Saban; Solmaz, Merve; Onal, Ozkan

2017-03-01

Retinal ischemia-reperfusion (IR) injury is associated with many ocular diseases. Retinal IR injury leads to the death of retinal ganglion cells (RGCs), loss of retinal function and ultimately vision loss. The aim of this study was to show the protective effects of prophylactic ozone administration against retinal IR injury. A sham group (S) (n = 7) was administered physiological saline (PS) intraperitoneally (i.p.) for 7 d. An ischemia reperfusion (IR) group (n = 7) was subjected to retinal ischemia followed by reperfusion for 2 h. An ozone group (O) (n = 7) was administered 1 mg/kg of ozone i.p. for 7 d. In the ozone + IR (O + IR) group (n = 7), 1 mg/kg of ozone was administered i.p. for 7 d before the IR procedure and at 8 d, the IR injury was created (as in IR group). The rats were anesthetized after second hour of reperfusion and their intracardiac blood was drawn completely and they were sacrificed. Blood samples were sent to a laboratory for analysis of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total oxidant score (TOS) and total antioxidant capacity (TAC). The degree of retinal injury was evaluated according to changes in retinal cells and necrotic and apoptotic cells using the TUNEL method. Data were evaluated statistically with the Kruskal-Wallis test. The number of RGCs and the inner retinal thickness were significantly decreased after ischemia, and treatment with ozone significantly inhibited retinal ischemic injury. In the IR group, the degree of retinal injury was found to be the highest. In the O + IR group, retinal injury was found to be decreased in comparison to the IR group. In the ozone group without retinal IR injury, the retinal injury score was the lowest. The differences in the antioxidant parameters SOD, GSH-Px and TAC were increased in the ozone group and the lowest in the IR group. The oxidant parameters MDA and TOS were found to be the highest in the IR group and

Retinal detachment

PubMed Central

2009-01-01

Introduction Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment, where a retinal "break" allows the ingress of fluid from the vitreous cavity to the subretinal space, resulting in retinal separation. It occurs in about 1 in 10,000 people a year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression from retinal breaks or lattice degeneration to retinal detachment? What are the effects of different surgical interventions in people with rhegmatogenous retinal detachment? What are the effects of interventions to treat proliferative vitreoretinopathy occurring as a complication of retinal detachment or previous treatment for retinal detachment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: corticosteroids; cryotherapy; daunorubicin; fluorouracil plus low-molecular-weight heparin; laser photocoagulation; pneumatic retinopexy; scleral buckling; short-acting or long-acting gas tamponade; silicone oil tamponade; and vitrectomy. PMID:19450333

Retinal detachment

PubMed Central

2010-01-01

Introduction Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment, where a retinal "break" allows the ingress of fluid from the vitreous cavity to the subretinal space, resulting in retinal separation. It occurs in about 1 in 10,000 people a year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression from retinal breaks or lattice degeneration to retinal detachment? What are the effects of different surgical interventions in people with rhegmatogenous retinal detachment? What are the effects of interventions to treat proliferative vitreoretinopathy occurring as a complication of retinal detachment or previous treatment for retinal detachment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: corticosteroids, cryotherapy, daunorubicin, fluorouracil plus low molecular weight heparin, laser photocoagulation, pneumatic retinopexy, scleral buckling, short-acting or long-acting gas tamponade, silicone oil tamponade, and vitrectomy. PMID:21406128

Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes.

PubMed

Uemura, Akiyoshi; Kusuhara, Sentaro; Wiegand, Stanley J; Yu, Ruth T; Nishikawa, Shin-ichi

2006-02-01

In response to hypoxia, hypoxia-inducible factors act as the primary proangiogenic triggers by regulating transcription levels of target genes, including VEGF. However, little is known about the specific factors that control other components of the angiogenic process, particularly formation of matrix scaffolds that promote adhesion and migration of endothelial cells. We show that in the postnatal mouse retina, the orphan nuclear receptor tailless (Tlx) is strongly expressed in the proangiogenic astrocytes, which secrete VEGF and fibronectin. Tlx expression by retinal astrocytes is controlled by oxygen concentration and rapidly downregulated upon contact with blood vessels. In mice null for Tlx, retinal astrocytes maintain VEGF expression; however, the extracellular assembly of fibronectin matrices by astrocytes is severely impaired, leading to defective scaffold formation and a complete failure of normal retinal vascular development. This work identifies Tlx as an essential component of the molecular network involved in the hypoxia-inducible proangiogenic switch in retinal astrocytes.

Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes

PubMed Central

Uemura, Akiyoshi; Kusuhara, Sentaro; Wiegand, Stanley J.; Yu, Ruth T.; Nishikawa, Shin-Ichi

2006-01-01

In response to hypoxia, hypoxia-inducible factors act as the primary proangiogenic triggers by regulating transcription levels of target genes, including VEGF. However, little is known about the specific factors that control other components of the angiogenic process, particularly formation of matrix scaffolds that promote adhesion and migration of endothelial cells. We show that in the postnatal mouse retina, the orphan nuclear receptor tailless (Tlx) is strongly expressed in the proangiogenic astrocytes, which secrete VEGF and fibronectin. Tlx expression by retinal astrocytes is controlled by oxygen concentration and rapidly downregulated upon contact with blood vessels. In mice null for Tlx, retinal astrocytes maintain VEGF expression; however, the extracellular assembly of fibronectin matrices by astrocytes is severely impaired, leading to defective scaffold formation and a complete failure of normal retinal vascular development. This work identifies Tlx as an essential component of the molecular network involved in the hypoxia-inducible proangiogenic switch in retinal astrocytes. PMID:16424942

Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

PubMed Central

Makino, Ayako; Firth, Amy L.; Yuan, Jason X.-J.

2017-01-01

The pulmonary circulation is a low resistance and low pressure system. Sustained pulmonary vasoconstriction and excessive vascular remodeling often occur under pathophysiological conditions such as in patients with pulmonary hypertension. Pulmonary vasoconstriction is a consequence of smooth muscle contraction. Many factors released from the endothelium contribute to regulating pulmonary vascular tone, while the extracellular matrix in the adventitia is the major determinant of vascular wall compliance. Pulmonary vascular remodeling is characterized by adventitial and medial hypertrophy due to fibroblast and smooth muscle cell proliferation, neointimal proliferation, intimal, and plexiform lesions that obliterate the lumen, muscularization of precapillary arterioles, and in situ thrombosis. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction, while increased release of mitogenic factors, upregulation (or downregulation) of ion channels and transporters, and abnormalities in intracellular signaling cascades are key to the remodeling of the pulmonary vasculature. Changes in the expression, function, and regulation of ion channels in PASMC and pulmonary arterial endothelial cells play an important role in the regulation of vascular tone and development of vascular remodeling. This article will focus on describing the ion channels and transporters that are involved in the regulation of pulmonary vascular function and structure and illustrating the potential pathogenic role of ion channels and transporters in the development of pulmonary vascular disease. PMID:23733654

Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense Physical Activity.

PubMed

Coca, Mircea; Tecle, Nahom; Amde, Wendewessen; Mehta, Ankur

2017-08-23

We report a case of combined central retinal vein occlusion and branch retinal artery occlusion. A previously healthy 47-year-old male presented with decreased vision in the right eye after completing a half marathon. A fundus exam and retinal imaging revealed a combined central retinal vein and branch retinal artery occlusion. In the present report, we review the literature and discuss the possible mechanisms behind combined retinal vessel occlusions. To our knowledge, this is the first reported case of combined central retinal vein occlusion and branch retinal artery occlusion following intense exercise.

Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense Physical Activity

PubMed Central

Tecle, Nahom; Amde, Wendewessen; Mehta, Ankur

2017-01-01

We report a case of combined central retinal vein occlusion and branch retinal artery occlusion. A previously healthy 47-year-old male presented with decreased vision in the right eye after completing a half marathon. A fundus exam and retinal imaging revealed a combined central retinal vein and branch retinal artery occlusion. In the present report, we review the literature and discuss the possible mechanisms behind combined retinal vessel occlusions. To our knowledge, this is the first reported case of combined central retinal vein occlusion and branch retinal artery occlusion following intense exercise. PMID:29067224

A Bioreactor to Identify the Driving Mechanical Stimuli of Tissue Growth and Remodeling.

PubMed

van Kelle, Mathieu A J; Oomen, Pim J A; Bulsink, Jurgen A; Janssen-van den Broek, Marloes W J T; Lopata, Richard G P; Rutten, Marcel C M; Loerakker, Sandra; Bouten, Carlijn V C

2017-06-01

Tissue growth and remodeling are essential processes that should ensure long-term functionality of tissue-engineered (TE) constructs. Even though it is widely recognized that these processes strongly depend on mechanical stimuli, the underlying mechanisms of mechanically induced growth and remodeling are only partially understood. It is generally accepted that cells sense mechanical changes and respond by altering their surroundings, by means of extracellular matrix growth and remodeling, in an attempt to return to a certain preferred mechanical homeostatic state. However, the exact mechanical cues that trigger cells to synthesize and remodel their environment remain unclear. To identify the driving mechanical stimuli of these processes, it is critical to be able to temporarily follow the mechanical state of developing tissues under physiological loading conditions. Therefore, a novel "versatile tissue growth and remodeling" (Vertigro) bioreactor was developed that is capable of tissue culture and mechanical stimulation for a prolonged time period, while simultaneously performing mechanical testing. The Vertigro's unique two-chamber design allows easy, sterile handling of circular 3D TE constructs in a dedicated culture chamber, while a separate pressure chamber facilitates a pressure-driven dynamic loading regime during culture. As a proof-of-concept, temporal changes in the mechanical state of cultured tissues were quantified using nondestructive mechanical testing by means of a classical bulge test, in which the tissue displacement was tracked using ultrasound imaging. To demonstrate the successful development of the bioreactor system, compositional, structural, and geometrical changes were qualitatively and quantitatively assessed using a series of standard analysis techniques. With this bioreactor and associated mechanical analysis technique, a powerful toolbox has been developed to quantitatively study and identify the driving mechanical stimuli of engineered

Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis.

PubMed

Arcinue, Cheryl A; Bartsch, Dirk-Uwe; El-Emam, Sharif Y; Ma, Feiyan; Doede, Aubrey; Sharpsten, Lucie; Gomez, Maria Laura; Freeman, William R

2015-01-01

To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

Mechanically triggered heterolytic unzipping of a low-ceiling-temperature polymer

NASA Astrophysics Data System (ADS)

Diesendruck, Charles E.; Peterson, Gregory I.; Kulik, Heather J.; Kaitz, Joshua A.; Mar, Brendan D.; May, Preston A.; White, Scott R.; Martínez, Todd J.; Boydston, Andrew J.; Moore, Jeffrey S.

2014-07-01

Biological systems rely on recyclable materials resources such as amino acids, carbohydrates and nucleic acids. When biomaterials are damaged as a result of aging or stress, tissues undergo repair by a depolymerization-repolymerization sequence of remodelling. Integration of this concept into synthetic materials systems may lead to devices with extended lifetimes. Here, we show that a metastable polymer, end-capped poly(o-phthalaldehyde), undergoes mechanically initiated depolymerization to revert the material to monomers. Trapping experiments and steered molecular dynamics simulations are consistent with a heterolytic scission mechanism. The obtained monomer was repolymerized by a chemical initiator, effectively completing a depolymerization-repolymerization cycle. By emulating remodelling of biomaterials, this model system suggests the possibility of smart materials where aging or mechanical damage triggers depolymerization, and orthogonal conditions regenerate the polymer when and where necessary.

The Effects of Transient Retinal Detachment on Cavity Size and Glial and Neural Remodeling in a Mouse Model of X-Linked Retinoschisis

PubMed Central

Luna, Gabriel; Kjellstrom, Sten; Verardo, Mark R.; Lewis, Geoffrey P.; Byun, Jiyun; Sieving, Paul A.; Fisher, Steven K.

2009-01-01

Purpose To determine the cellular consequences of retinal detachment in retinoschisin knockout (Rs1-KO) mice, a model for retinoschisin in humans. Methods Experimental retinal detachments (RDs) were induced in the right eyes of both Rs1-KO and wild-type (wt) control mice. Immunocytochemistry was performed on retinal tissue at 1, 7, or 28 days after RD with antibodies to anti-GFAP, -neurofilament, and -rod opsin to examine cellular changes after detachment. Images of the immunostained tissue were captured by laser scanning confocal microscopy. Quantitative analysis was performed to measure the number of Hoechst-stained photoreceptor nuclei and their density, number, and size of inner retinal cavities, as well as the number of subretinal glial scars. Results Since detachments were created with balanced salt solution, by examination, all retinas had spontaneously reattached by 1 day. Cellular responses common to many photoreceptor degenerations occurred in the nondetached retinas of Rs1-KO mice, and, of importance, RD did not appear to significantly accentuate these responses. The number of schisis cavities was not changed after detachment, but their size was reduced. Conclusions These data indicate that large short-term RD in Rs1-KO mice, followed by a period of reattachment may cause a slight increase in photoreceptor cell death, but detachments do not accentuate the gliosis and neurite sprouting already present and may in fact reduce the size of existing retinal cavities. This finding suggests that performing subretinal injections to deliver therapeutic agents may be a viable option in the treatment of patients with retinoschisis without causing significant cellular damage to the retina. PMID:19387072

Distinct retinal pathways drive spatial orientation behaviors in zebrafish navigation.

PubMed

Burgess, Harold A; Schoch, Hannah; Granato, Michael

2010-02-23

Navigation requires animals to adjust ongoing movements in response to pertinent features of the environment and select between competing target cues. The neurobiological basis of navigational behavior in vertebrates is hard to analyze, partly because underlying neural circuits are experience dependent. Phototaxis in zebrafish is a hardwired navigational behavior, performed at a stage when larvae swim by using a small repertoire of stereotyped movements. We established conditions to elicit robust phototaxis behavior and found that zebrafish larvae deploy directional orienting maneuvers and regulate forward swimming speed to navigate toward a target light. Using genetic analysis and targeted laser ablations, we show that retinal ON and OFF pathways play distinct roles during phototaxis. The retinal OFF pathway controls turn movements via retinotectal projections and establishes correct orientation by causing larvae to turn away from nontarget areas. In contrast, the retinal ON pathway activates the serotonergic system to trigger rapid forward swimming toward the target. Computational simulation of phototaxis with an OFF-turn, ON-approach algorithm verifies that our model accounts for key features of phototaxis and provides a simple and robust mechanism for behavioral choice between competing targets. Copyright 2010 Elsevier Ltd. All rights reserved.

No-Regrets Remodeling, 2nd Edition

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

None

2013-12-01

No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

Retinal detachment

PubMed Central

2014-01-01

Introduction Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment, where a retinal 'break' allows the ingress of fluid from the vitreous cavity to the subretinal space, resulting in retinal separation. It occurs in about 1 in 10,000 people a year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different surgical interventions in people with rhegmatogenous retinal detachment? What are the effects of interventions to treat proliferative vitreoretinopathy occurring as a complication of retinal detachment or previous treatment for retinal detachment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 14 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: corticosteroids, daunorubicin, fluorouracil plus low molecular weight heparin, pneumatic retinopexy, scleral buckling, short-acting or long-acting gas tamponade, silicone oil tamponade, and vitrectomy. PMID:24807890

Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways: Potential for Treating Age-related Retinal Degeneration

PubMed Central

Haeri, Mohammad; Knox, Barry E

2012-01-01

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) and their aggregation impair normal cellular function and can be toxic, leading to cell death. Prolonged expression of misfolded proteins triggers ER stress, which initiates a cascade of reactions called the unfolded protein response (UPR). Protein misfolding is the basis for a variety of disorders known as ER storage or conformational diseases. There are an increasing number of eye disorders associated with misfolded proteins and pathologic ER responses, including retinitis pigmentosa (RP). Herein we review the basic cellular and molecular biology of UPR with focus on pathways that could be potential targets for treating retinal degenerative diseases. PMID:22737387

Retinal input to efferent target amacrine cells in the avian retina

PubMed Central

Lindstrom, Sarah H.; Azizi, Nason; Weller, Cynthia; Wilson, Martin

2012-01-01

The bird visual system includes a substantial projection, of unknown function, from a midbrain nucleus to the contralateral retina. Every centrifugal, or efferent, neuron originating in the midbrain nucleus makes synaptic contact with the soma of a single, unique amacrine cell, the target cell (TC). By labeling efferent neurons in the midbrain we have been able to identify their terminals in retinal slices and make patch clamp recordings from TCs. TCs generate Na+ based action potentials triggered by spontaneous EPSPs originating from multiple classes of presynaptic neurons. Exogenously applied glutamate elicited inward currents having the mixed pharmacology of NMDA, kainate and inward rectifying AMPA receptors. Exogenously applied GABA elicited currents entirely suppressed by GABAzine, and therefore mediated by GABAA receptors. Immunohistochemistry showed the vesicular glutamate transporter, vGluT2, to be present in the characteristic synaptic boutons of efferent terminals, whereas the GABA synthetic enzyme, GAD, was present in much smaller processes of intrinsic retinal neurons. Extracellular recording showed that exogenously applied GABA was directly excitatory to TCs and, consistent with this, NKCC, the Cl− transporter often associated with excitatory GABAergic synapses, was identified in TCs by antibody staining. The presence of excitatory retinal input to TCs implies that TCs are not merely slaves to their midbrain input; instead, their output reflects local retinal activity and descending input from the midbrain. PMID:20650017

Chromatin Remodeling and Plant Immunity.

PubMed

Chen, W; Zhu, Q; Liu, Y; Zhang, Q

Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

[Retinal detachment in HIV-infected patients with cytomegalovirus retinitis].

PubMed

Onishchenko, A L; Kolbasko, A V; Tatarnikova, G N; Grebenchuk, O S

2014-01-01

The authors present their own clinical experience in three HIV-infected patients with cytomegalovirus retinitis aged from 8 to 36 years. Detailed analysis of the results of physical and laboratory examinations is provided. Given short life expectancy for these patients, the authors pose a deontological question as to whether or not active treatment of retinal detachment in patients with AIDS and CMV retinitis is reasonable.

Long-term results of repeated anti-vascular endothelial growth factor therapy in eyes with retinal pigment epithelial tears.

PubMed

Moreira, Carlos A; Arana, Luis A; Zago, Rommel J

2013-02-01

To evaluate the long-term results of retinal pigment epithelium tears in eyes treated with repeated anti-vascular endothelial growth factor (VEGF) therapy. Five patients with retinal pigment epithelial tears (without foveal center involvement) after anti-VEGF injection were studied retrospectively. Mean follow-up time was 52 months, with measurements of visual acuity and evaluation of macular findings by angiography and optical coherence tomography during this period. All eyes had a persistent submacular neovascular membrane 30 days after the tear. An anti-VEGF drug was reinjected until the membranes stopped leaking. The mean initial visual acuity immediately after the tear was 20/160, and the mean final visual acuity was 20/60. The number of anti-VEGF reinjections varied from two to eight during the follow-up period. Long-term optical coherence tomography analysis showed reduced fluid and remodeling of the torn retinal pigment epithelium. Long-term visual results with repeated anti-VEGF therapy are not as devastating as suggested previously. Visual acuity and metamorphopsia improve with time as long as the neovascular membrane is inactive. Optical coherence tomography changes in the macular area reflect the visual acuity improvement.

Ischemia Reperfusion Injury Triggers TNFα Induced-Necroptosis in Rat Retina.

PubMed

Kim, Cho Rong; Kim, Jie Hyun; Park, Hae-Young Lopilly; Park, Chan Kee

2017-05-01

A recent study revealed a novel form of cell death, termed necroptosis, or programmed necrosis. Previous research indicated that after ischemia-reperfusion (IR) injury to the retina, Tumor Necrosis Factor α (TNFα) is increased, which may activate necroptosis. This study observed macroglial cell activation, and in particular, astrocyte activation, after the release of TNFα and other necroptosis factors in the rat retina due to IR. IR was induced in the retinas of adult male Sprague-Dawley rats by increasing the intraocular pressure to 160 mmHg and then allowing reperfusion. In addition, to inhibit necroptosis, Nec-1 (necrostatin-1) was injected intravitreally after IR. Rats were sacrificed after reperfusion at 12 hours, 1, 3, and 5 days, and 1 and 2 weeks. Retinas from each time point were analyzed by immunohistochemistry (IHC) and Western blotting (WB) to identify the initiator of necroptosis, TNFα, the expression of necroptosis factors, such as receptor interacting protein (RIP) 1, 3, and inactive caspase 8, and Brn3a. Cell death in the IR-injured retinas was identified by cell counting. We found decreased retinal cell numbers in the inner and outer nuclear layers (INL and ONL), as well as in the ganglion cell layer (GCL). Increased glial cell activation was detected by using glial fibrillary acidic protein (GFAP) IHC. TNFα, RIP1, RIP3, and inactive caspase 8 were mainly expressed in the GCL after IR, as determined by IHC and WB. Nec-1 inhibited RIP1, a necroptosis factor, indicating protection against retinal cell loss after IR injury. We showed that IR injury triggered increases in both activation of astrocytes and the expression of TNFα. In addition, TNFα, which was activated by IR, triggered the release of necroptosis factors, particularly, in GCL. Inhibition of necroptosis using Nec-1 decreased the level of RIP1 and retinal cell loss in IR-injured retinas.

The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities

PubMed Central

Frangogiannis, Nikolaos G

2014-01-01

Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-Like Receptor (TLR)/Interleukin (IL)-1 signaling, resulting in activation of the Nuclear Factor (NF)-κB system and induction of chemokines, cytokines and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment and resolution of the post-infarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury. PMID:24072174

Evaluation of hyaloid-retinal relationship during triamcinolone-assisted vitrectomy for primary rhegmatogenous retinal detachment.

PubMed

Sundar, Dheepak; Takkar, Brijesh; Venkatesh, Pradeep; Chawla, Rohan; Temkar, Shreyas; Azad, Shorya Vardhan; Vohra, Rajpal

2018-03-01

To determine hyaloid-retinal relationship in primary rhegmatogenous retinal detachment during vitreous surgery. This is a prospective, interventional study of patients (n = 72) undergoing triamcinolone-assisted 25G vitreous surgery for primary rhegmatogenous retinal detachment. Hyaloid-retinal relationship was noted intraoperatively to identify regions and patterns of firm attachment and was classified into subgroups. Analysis was done to determine association between hyaloid-retinal relationship patterns and preoperative findings: posterior vitreous detachment, proliferative vitreoretinopathy, type of retinal tear, the presence of peripheral degenerations, and postoperative outcomes. Three patterns of hyaloid-retinal relationship were identified: type1 (complete absence of posterior vitreous detachment (21%)), type 2 (incomplete posterior vitreous detachment (47%)) and type 3 (complete posterior vitreous detachment (32%)). Posterior vitreous detachment in some form was present in 84% of the cases with retinal tears as the causative break but none of the cases with retinal holes (p < 0.001). None of the cases with vitreoretinal degeneration had complete posterior vitreous detachment (p = 0.001). 69% of proliferative vitreoretinopathy-C cases had type 1 hyaloid-retinal relationship as compared to 11% cases with no proliferative vitreoretinopathy (p < 0.001). Proliferative vitreoretinopathy-related anatomical failure was seen in 7.5%, and 80% of these eyes with recurrent RD had type 1 hyaloid-retinal relationship (p<0.001). Nearly half the patients diagnosed as complete posterior vitreous detachment preoperatively were found to have incomplete posterior vitreous detachment intraoperatively. Majority of the cases with rhegmatogenous retinal detachment have some form of strong vitreoretinal adhesion. Hyaloid-retinal relationship varies with types of retinal breaks, retinal degeneration, and proliferative vitreoretinopathy. Intraoperative hyaloid-retinal relationship is

Developing Extracellular Matrix Technology to Treat Retinal or Optic Nerve Injury

PubMed Central

van der Merwe, Yolandi

2015-01-01

Abstract Adult mammalian CNS neurons often degenerate after injury, leading to lost neurologic functions. In the visual system, retinal or optic nerve injury often leads to retinal ganglion cell axon degeneration and irreversible vision loss. CNS axon degeneration is increasingly linked to the innate immune response to injury, which leads to tissue-destructive inflammation and scarring. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling, over scarring, in various tissues and organs, including the peripheral nervous system. However, applying ECM technology to CNS injuries has been limited and virtually unstudied in the visual system. Here we discuss advances in deriving fetal CNS-specific ECMs, like fetal porcine brain, retina, and optic nerve, and fetal non-CNS-specific ECMs, like fetal urinary bladder, and the potential for using tissue-specific ECMs to treat retinal or optic nerve injuries in two platforms. The first platform is an ECM hydrogel that can be administered as a retrobulbar, periocular, or even intraocular injection. The second platform is an ECM hydrogel and polymer “biohybrid” sheet that can be readily shaped and wrapped around a nerve. Both platforms can be tuned mechanically and biochemically to deliver factors like neurotrophins, immunotherapeutics, or stem cells. Since clinical CNS therapies often use general anti-inflammatory agents, which can reduce tissue-destructive inflammation but also suppress tissue-reparative immune system functions, tissue-specific, ECM-based devices may fill an important need by providing naturally derived, biocompatible, and highly translatable platforms that can modulate the innate immune response to promote a positive functional outcome. PMID:26478910

Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury.

PubMed

Tong, Nianting; Zhang, Zhenzhen; Zhang, Wei; Qiu, Yating; Gong, Yuanyuan; Yin, Lili; Qiu, Qinghua; Wu, Xingwei

2013-01-01

Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood-retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy. Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio. Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.

Retinitis pigmentosa

MedlinePlus

... this page: //medlineplus.gov/ency/article/001029.htm Retinitis pigmentosa To use the sharing features on this page, please enable JavaScript. Retinitis pigmentosa is an eye disease in which there is ...

[Early therapeutic trials for retinitis pigmentosa].

PubMed

Dufier, Jean-Louis

2003-01-01

Non syndromic forms of Retinitis Pigmentosa (RP) constitute a collection of clinically and genetically heterogeneous inherited retinal degenerative diseases. They are characterized by a bilateral progressive visual loss susceptible to cause blindness. These diseases are transmitted through pedigrees according to all known modes of inheritance. They are bilateral and usually start during infancy. However, very early clinical presentations exist, such as those observed in children affected by Leber Congenital Amaurosis, as well as late onset autosomal dominant forms of retinitis pigmentosa. The characteristic clinical aspect of the rod-cone RP dystrophies is marked by alterations of the peripheral retina associated with a night blindness and a progressive narrowing of the visual field. The ophthalmoscopic examination of RP patients commonly reveals thin retinal arteries and scattered pigmentary accumulations. In contrast, there are cone rod retinal dystrophies whose onset is marked by a decreased visual acuity before the appearance of any visual field alteration. Some forms of RPs display an ocular fundus devoid of any pigmentary alteration. Syndromic forms of RPs are not uncommon. The association of deafness with RP is detected in nearly 30% of the patients. Other associations with RP can include mental deficiency, facial dysmorphy, microcephaly, obesity, kidney deficiency, immune deficiencies, metabolic disorders. The existence of such syndromic forms of RP localizes RPs at the crossroad of several medical specialties. A long lasting collaboration between our department of ophthalmology and the department of medical genetics of the Necker-Sick Children Hospital has allowed us to establish numerous genotype-phenotype correlations, especially in LCA and Stargardt's disease. ABCR gene mutations cause Stargardt disease. ABCR mutations may also cause some types of Ages Related Macular Degenerations (AMD). Nowadays, there is no known efficient therapy available for

Deciliation Is Associated with Dramatic Remodeling of Epithelial Cell Junctions and Surface Domains

PubMed Central

Overgaard, Christian E.; Sanzone, Kaitlin M.; Spiczka, Krystle S.; Sheff, David R.; Sandra, Alexander

2009-01-01

Stress-induced shedding of motile cilia (autotomy) has been documented in diverse organisms and likely represents a conserved cellular reaction. However, little is known about whether primary cilia are shed from mammalian epithelial cells and what impact deciliation has on polarized cellular organization. We show that several chemically distinct agents trigger autotomy in epithelial cells. Surprisingly, deciliation is associated with a significant, but reversible increase in transepithelial resistance. This reflects substantial reductions in tight junction proteins associated with “leaky” nephron segments (e.g., claudin-2). At the same time, apical trafficking of gp80/clusterin and gp114/CEACAM becomes randomized, basal-lateral delivery of Na,K-ATPase is reduced, and expression of the nonciliary apical protein gp135/podocalyxin is greatly decreased. However, ciliogenesis-impaired MDCK cells do not undergo continual junction remodeling, and mature cilia are not required for autotomy-associated remodeling events. Deciliation and epithelial remodeling may be mechanistically linked processes, because RNAi-mediated reduction of Exocyst subunit Sec6 inhibits ciliary shedding and specifically blocks deciliation-associated down-regulation of claudin-2 and gp135. We propose that ciliary autotomy represents a signaling pathway that impacts the organization and function of polarized epithelial cells. PMID:19005211

CMV retinitis

MedlinePlus

Cytomegalovirus (CMV) retinitis is a viral infection of the retina of the eye resulting in inflammation. ... CMV retinitis is caused by a member of a group of herpes-type viruses. Infection with CMV ...

The Dynamic Sclera: Extracellular Matrix Remodeling in Normal Ocular Growth and Myopia Development

PubMed Central

Harper, Angelica R.; Summers, Jody A.

2014-01-01

Myopia is a common ocular condition, characterized by excessive elongation of the ocular globe. The prevalence of myopia continues to increase, particularly among highly educated groups, now exceeding 80% in some groups. In parallel with the increased prevalence of myopia, are increases in associated blinding ocular conditions including glaucoma, retinal detachment and macular degeneration, making myopia a significant global health concern. The elongation of the eye is closely related to the biomechanical properties of the sclera, which in turn are largely dependent on the composition of the scleral extracellular matrix. Therefore an understanding of the cellular and extracellular events involved in the regulation of scleral growth and remodeling during childhood and young adulthood will provide future avenues for the treatment of myopia and its associated ocular complications. PMID:25819458

The Neural Circuit Mechanisms Underlying the Retinal Response to Motion Reversal

PubMed Central

Chen, Eric Y.; Chou, Janice; Park, Jeongsook; Schwartz, Greg

2014-01-01

To make up for delays in visual processing, retinal circuitry effectively predicts that a moving object will continue moving in a straight line, allowing retinal ganglion cells to anticipate the object's position. However, a sudden reversal of motion triggers a synchronous burst of firing from a large group of ganglion cells, possibly signaling a violation of the retina's motion prediction. To investigate the neural circuitry underlying this response, we used a combination of multielectrode array and whole-cell patch recordings to measure the responses of individual retinal ganglion cells in the tiger salamander to reversing stimuli. We found that different populations of ganglion cells were responsible for responding to the reversal of different kinds of objects, such as bright versus dark objects. Using pharmacology and designed stimuli, we concluded that ON and OFF bipolar cells both contributed to the reversal response, but that amacrine cells had, at best, a minor role. This allowed us to formulate an adaptive cascade model (ACM), similar to the one previously used to describe ganglion cell responses to motion onset. By incorporating the ON pathway into the ACM, we were able to reproduce the time-varying firing rate of fast OFF ganglion cells for all experimentally tested stimuli. Analysis of the ACM demonstrates that bipolar cell gain control is primarily responsible for generating the synchronized retinal response, as individual bipolar cells require a constant time delay before recovering from gain control. PMID:25411485

Retinitis Pigmentosa.

ERIC Educational Resources Information Center

Carr, Ronald E.

1979-01-01

The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

Laser-induced retinal injury thresholds: variation with retinal irradiated area

NASA Astrophysics Data System (ADS)

Lund, David J.; Schulmeister, Karl; Seiser, Bernhard; Edthofer, Florian

2005-04-01

The retinal injury threshold for exposure to a laser source varies as a function of the irradiated area on the retina. Currently accepted guidelines for the safe use of lasers provide that the MPE will increase as the diameter of the irradiated area for retinal diameters between 25 mm and 1700 mm, based on the ED50 data available in the late 1970s. Recent studies by Zuclich and Lund produced data showing that the ED50 for ns-duration exposures at 532 nm and ms duration exposures at 590 nm varied as the square of the diameter of the irradiated area on the retina. This paper will discuss efforts to resolve the disagreement between the new data and the earlier data though an analysis of all accessible data relating the retinal injury threshold to the diameter of the incident beam on the retina and through simulations using computer models of laser-induced injury. The results show that the retinal radiant exposure required to produce retinal injury is a function of both exposure duration and retinal irradiance diameter and that the current guidelines for irradiance diameter dependence do not accurately reflect the variation of the threshold data.

Callus remodelling model

NASA Astrophysics Data System (ADS)

Miodowska, Justyna; Bielski, Jan; Kromka-Szydek, Magdalena

2018-01-01

The objective of this paper is to investigate the healing process of the callus using bone remodelling approach. A new mathematical model of bone remodelling is proposed including both underload and overload resorption, as well as equilibrium and bone growth states. The created model is used to predict the stress-stimulated change in the callus density. The permanent and intermittent loading programs are considered. The analyses indicate that obtaining a sufficiently high values of the callus density (and hence the elasticity) modulus is only possible using time-varying load parameters. The model predictions also show that intermittent loading program causes delayed callus healing. Understanding how mechanical conditions influence callus remodelling process may be relevant in the bone fracture treatment and initial bone loading during rehabilitation.

Retinal Detachment Associated with AIDS-Related Cytomegalovirus Retinitis: Risk Factors in a Resource-Limited Setting

PubMed Central

Yen, Michael; Chen, Jenny; Ausayakhun, Somsanguan; Kunavisarut, Paradee; Vichitvejpaisal, Pornpattana; Ausayakhun, Sakarin; Jirawison, Choeng; Shantha, Jessica; Holland, Gary N; Heiden, David; Margolis, Todd P; Keenan, Jeremy D

2014-01-01

Purpose To determine risk factors predictive of retinal detachment in patients with cytomegalovirus (CMV) retinitis in a setting with limited access to ophthalmic care. Design Case-control study. Methods Sixty-four patients with CMV retinitis and retinal detachment were identified from the Ocular Infectious Diseases and Retina Clinics at Chiang Mai University. Three control patients with CMV retinitis but no retinal detachment were selected for each case, matched by calendar date. The medical records of each patient were reviewed, with patient-level and eye-level features recorded for the clinic visit used to match cases and controls, and also for the initial clinic visit at which CMV retinitis was diagnosed. Risk factors for retinal detachment were assessed separately for each of these time points using multivariate conditional logistic regression models that included 1 eye from each patient. Results Patients with a retinal detachment were more likely than controls to have low visual acuity (OR, 1.24 per line of worse vision on the logMAR scale; 95%CI, 1.16-1.33) and bilateral disease (OR, 2.12; 95%CI, 0.92-4.90). Features present at the time of the initial diagnosis of CMV retinitis that predicted subsequent retinal detachment included bilateral disease (OR, 2.68; 95%CI, 1.18-6.08) and lesion size (OR, 2.64 per 10% increase in lesion size; 95%CI, 1.41-4.94). Conclusion Bilateral CMV retinitis and larger lesion sizes, each of which is a marker of advanced disease, were associated with subsequent retinal detachment. Earlier detection and treatment may reduce the likelihood that patients with CMV retinitis develop a retinal detachment. PMID:25448999

Retinal detachment associated with AIDS-related cytomegalovirus retinitis: risk factors in a resource-limited setting.

PubMed

Yen, Michael; Chen, Jenny; Ausayakhun, Somsanguan; Kunavisarut, Paradee; Vichitvejpaisal, Pornpattana; Ausayakhun, Sakarin; Jirawison, Choeng; Shantha, Jessica; Holland, Gary N; Heiden, David; Margolis, Todd P; Keenan, Jeremy D

2015-01-01

To determine risk factors predictive of retinal detachment in patients with cytomegalovirus (CMV) retinitis in a setting with limited access to ophthalmic care. Case-control study. Sixty-four patients with CMV retinitis and retinal detachment were identified from the Ocular Infectious Diseases and Retina Clinics at Chiang Mai University. Three control patients with CMV retinitis but no retinal detachment were selected for each case, matched by calendar date. The medical records of each patient were reviewed, with patient-level and eye-level features recorded for the clinic visit used to match cases and controls, and also for the initial clinic visit at which CMV retinitis was diagnosed. Risk factors for retinal detachment were assessed separately for each of these time points using multivariate conditional logistic regression models that included 1 eye from each patient. Patients with a retinal detachment were more likely than controls to have low visual acuity (odds ratio [OR], 1.24 per line of worse vision on the logMAR scale; 95% confidence interval [CI], 1.16-1.33) and bilateral disease (OR, 2.12; 95% CI, 0.92-4.90). Features present at the time of the initial diagnosis of CMV retinitis that predicted subsequent retinal detachment included bilateral disease (OR, 2.68; 95% CI, 1.18-6.08) and lesion size (OR, 2.64 per 10% increase in lesion size; 95% CI, 1.41-4.94). Bilateral CMV retinitis and larger lesion sizes, each of which is a marker of advanced disease, were associated with subsequent retinal detachment. Earlier detection and treatment may reduce the likelihood that patients with CMV retinitis develop a retinal detachment. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

PubMed

Park, Susanna S

2016-04-01

Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

Retinal Diseases

MedlinePlus

... You are here Home Listen Retinal Diseases Macular Degeneration Age-related macular degeneration (AMD) is a retinal degenerative disease that causes ... is the most common form of inherited juvenile macular degeneration. The progressive vision loss associated with Stargardt disease ...

Mapping by VESGEN of Blood Vessels in the Retinas of ISS Crew Members and Bed Rest Subjects for Increased Understanding of VIIP

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, P. A.; Vizzeri, G.; Tabbi, G.; Zanello, S. B.; Ploutz-Snyder, R.

2014-01-01

Research by NASA has established that significant risks for visual impairment in association with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema, and cotton wool spots. Much remains to be learned about the etiology of VIIP before effective countermeasures can be developed. Contributions of retinal vascular remodeling to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive pathophysiological remodeling of the retinal microvasculature. Although ophthalmic science and clinical practice are now highly sophisticated at detecting indirect, secondary signs of vascular remodeling such as cotton wool spots that arise during the progression of retinal vascular diseases, methods for quantifying direct, primary vascular changes are not yet established. To help develop insightful analysis of retinal vascular remodeling for aerospace medicine, we will map and quantify by our innovative VESsel GENeration Analysis (VESGEN) software the remodeling status of retinal blood vessels in crew members before and after ISS missions, and in healthy human subjects before and after head-down tilt bed rest. For this proof-of-concept study, we hypothesize that pathophysiological remodeling of retinal blood vessels occurs in coordination with microgravity-induced fluid shifts prior to development of visual impairments. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage progression of the visually impairing, potentially blinding disease, diabetic retinopathy.

The inflammatory response in myocardial injury, repair and remodeling

PubMed Central

Frangogiannis, Nikolaos G.

2015-01-01

Myocardial infarction triggers an intense inflammatory response that is essential for cardiac repair, but which is also implicated in the pathogenesis of post-infarction remodeling and heart failure. Signals in the infarcted myocardium activate toll-like receptor signalling, while complement activation and generation of reactive oxygen species induce cytokine and chemokine upregulation. Leukocytes recruited remove dead cells and matrix debris by phagocytosis, while setting the stage for scar formation. Timely repression of the inflammatory response is critical for effective healing and followed by activation of infarct myofibroblasts that secrete matrix proteins in the infarcted area. Members of the transforming growth factor-β family are critically involved in suppression of inflammation and activation of a pro-fibrotic program. Translation of these concepts in the clinic requires understanding of the pathophysiologic complexity and heterogeneity of post-infarction remodeling in human patients with myocardial infarction. Individuals with overactive and prolonged post-infarction inflammation might exhibit dilation and systolic dysfunction and benefit from targeted anti-IL-1 or anti-chemokine therapies, whereas patients with exaggerated fibrogenic reactions can develop diastolic heart failure and might require inhibition of the smad3 cascade. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to rationally implement inflammation-modulating strategies. PMID:24663091

Triggers and Anatomical Substrates in the Genesis and Perpetuation of Atrial Fibrillation

PubMed Central

Sánchez-Quintana, Damián; López-Mínguez, José Ramón; Pizarro, Gonzalo; Murillo, Margarita; Cabrera, José Angel

2012-01-01

The definition of atrial fibrillation (AF) as a functional electrical disorder does not reflect the significant underlying structural abnormalities. Atrial and Pulmonary Vein (PV) muscle sleeve microstructural remodeling is present, and establishes a vulnerable substrate for AF maintenance. In spite of an incomplete understanding of the anatomo-functional basis for AF, current evidence demonstrates that this arrhythmia usually requires a trigger for initiation and a vulnerable electrophysiological and/or anatomical substrate for maintenance. It is still unclear whether the trigger mechanisms include focal enhanced automaticity, triggered activity and/or micro re-entry from myocardial tissue. Initiation of AF can be favored by both parasympathetic and sympathetic stimulation, which also seem to play a role in maintaining AF. Finally, evolving clinical evidence demonstrates that inflammation is associated with new-onset and recurrent AF through a mechanism that possibly involves cellular degeneration, apoptosis, and subsequent atrial fibrosis. PMID:22920484

Pan-retinal characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina.

PubMed

Hilgen, Gerrit; Pirmoradian, Sahar; Pamplona, Daniela; Kornprobst, Pierre; Cessac, Bruno; Hennig, Matthias H; Sernagor, Evelyne

2017-02-10

We have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to different contrasts not only revealed a complex developmental profile for ON, OFF and ON-OFF responses, but also unveiled differences between dorsal and ventral RGC responses. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental profile of ON and OFF responses exhibited antagonistic behaviour, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive field (RF) center sizes decrease, spike-triggered averaged responses to white noise become stronger, and centers become more circular while maintaining differences between RGC types. We conclude that the maturation of retinal functionality is not spatially homogeneous, likely reflecting ecological requirements that favour earlier maturation of the dorsal retina.

Enhancement of P2X(7)-induced pore formation and apoptosis: an early effect of diabetes on the retinal microvasculature.

PubMed

Sugiyama, Tetsuya; Kobayashi, Masato; Kawamura, Hajime; Li, Qing; Puro, Donald G; Kobayshi, Masato

2004-03-01

A sight-threatening complication of diabetes is cell death in retinal capillaries. Currently, the mechanisms responsible for this classic manifestation of diabetic retinopathy remain uncertain. The hypothesis for the current study is that diabetes increases the vulnerability of retinal microvessels to the potentially lethal consequences of having their P2X(7) purinoceptors activated. A pathophysiological role is suspected for these receptor-operated channels because, in addition to transducing retinovascular responses to extracellular adenosine triphosphate (ATP), the sustained opening of these channels can induce the formation of large transmembrane pores. In pericyte-containing retinal microvessels that were freshly isolated from nondiabetic and streptozotocin-injected rats, cells with pores were identified by the uptake of YO-PRO-1. Cell viability was assayed by trypan blue dye exclusion, and cleaved caspase-3 immunoreactivity, TUNEL positivity, and nuclear morphology were used to detect apoptotic cells. Patch-clamp recordings assessed electrophysiological parameters. Activation of P2X(7) receptors caused large pores to form and apoptosis to occur in retinal capillaries of nondiabetic and diabetic rats. Of importance to diabetes, the agonist concentration needed to open pores and trigger apoptosis decreased markedly soon after the onset of streptozotocin-induced hyperglycemia. However, despite this increased sensitivity, diabetes minimally affected the P2X(7)-induced ionic currents. Thus, rather than upregulate the number of functional P2X(7) receptor/channels, diabetes appears to facilitate the channel-to-pore transition that occurs during activation of these purinoceptors. In this way, normally nonlethal concentrations of P2X(7) ligands may trigger apoptosis in microvessels of the diabetic retina. A diabetes-induced increase in the vulnerability of retinal microvessels to the lethal effect of P2X(7) receptor activation may be a previously unrecognized

Disorders of Bone Remodeling

PubMed Central

Feng, Xu; McDonald, Jay M.

2013-01-01

The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms. PMID:20936937

Retinal vasculopathy is reduced by dietary salt restriction: involvement of Glia, ENaCα, and the renin-angiotensin-aldosterone system.

PubMed

Deliyanti, Devy; Armani, Roksana; Casely, David; Figgett, William A; Agrotis, Alex; Wilkinson-Berka, Jennifer L

2014-09-01

Neovascularization and vaso-obliteration are vision-threatening events that develop by interactions between retinal vascular and glial cells. A high-salt diet is causal in cardiovascular and renal disease, which is linked to modulation of the renin-angiotensin-aldosterone system. However, it is not known whether dietary salt influences retinal vasculopathy and if the renin-angiotensin-aldosterone system is involved. We examined whether a low-salt (LS) diet influenced vascular and glial cell injury and the renin-angiotensin-aldosterone system in ischemic retinopathy. Pregnant Sprague Dawley rats were fed LS (0.03% NaCl) or normal salt (0.3% NaCl) diets, and ischemic retinopathy was induced in the offspring. An LS diet reduced retinal neovascularization and vaso-obliteration, the mRNA and protein levels of the angiogenic factors, vascular endothelial growth factor, and erythropoietin. Microglia, which influence vascular remodeling in ischemic retinopathy, were reduced by LS as was tumor necrosis factor-α. Macroglial Müller cells maintain the integrity of the blood-retinal barrier, and in ischemic retinopathy, LS reduced their gliosis and also vascular leakage. In retina, LS reduced mineralocorticoid receptor, angiotensin type 1 receptor, and renin mRNA levels, whereas, as expected, plasma levels of aldosterone and renin were increased. The aldosterone/mineralocorticoid receptor-sensitive epithelial sodium channel alpha (ENaCα), which is expressed in Müller cells, was increased in ischemic retinopathy and reduced by LS. In cultured Müller cells, high salt increased ENaCα, which was prevented by mineralocorticoid receptor and angiotensin type 1 receptor blockade. Conversely, LS reduced ENaCα, angiotensin type 1 receptor, and mineralocorticoid receptor expression. An LS diet reduced retinal vasculopathy, by modulating glial cell function and the retinal renin-angiotensin-aldosterone system. © 2014 American Heart Association, Inc.

Blue light effect on retinal pigment epithelial cells by display devices.

PubMed

Moon, Jiyoung; Yun, Jieun; Yoon, Yeo Dae; Park, Sang-Il; Seo, Young-Jun; Park, Won-Sang; Chu, Hye Yong; Park, Keun Hong; Lee, Myung Yeol; Lee, Chang Woo; Oh, Soo Jin; Kwak, Young-Shin; Jang, Young Pyo; Kang, Jong Soon

2017-05-22

Blue light has high photochemical energy and induces cell apoptosis in retinal pigment epithelial cells. Due to its phototoxicity, retinal hazard by blue light stimulation has been well demonstrated using high intensity light sources. However, it has not been studied whether blue light in the displays, emitting low intensity light, such as those used in today's smartphones, monitors, and TVs, also causes apoptosis in retinal pigment epithelial cells. We attempted to examine the blue light effect on human adult retinal epithelial cells using display devices with different blue light wavelength ranges, the peaks of which specifically appear at 449 nm, 458 nm, and 470 nm. When blue light was illuminated on A2E-loaded ARPE-19 cells using these displays, the display with a blue light peak at a shorter wavelength resulted in an increased production of reactive oxygen species (ROS). Moreover, the reduction of cell viability and induction of caspase-3/7 activity were more evident in A2E-loaded ARPE-19 cells after illumination by the display with a blue light peak at a shorter wavelength, especially at 449 nm. Additionally, white light was tested to examine the effect of blue light in a mixed color illumination with red and green lights. Consistent with the results obtained using only blue light, white light illuminated by display devices with a blue light peak at a shorter wavelength also triggered increased cell death and apoptosis compared to that illuminated by display devices with a blue light peak at longer wavelength. These results show that even at the low intensity utilized in the display devices, blue light can induce ROS production and apoptosis in retinal cells. Our results also suggest that the blue light hazard of display devices might be highly reduced if the display devices contain less short wavelength blue light.

Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients.

PubMed

Liu, Yong; Chen, Shao Jun; Li, Shi Ying; Qu, Ling Hui; Meng, Xiao Hong; Wang, Yi; Xu, Hai Wei; Liang, Zhi Qing; Yin, Zheng Qin

2017-09-29

Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients. In our pre-clinical study, purified human fetal-derived retinal progenitor cells (RPCs) were transplanted into the diseased retina of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. Based on these results, we conducted a phase I clinical trial to establish the safety and tolerability of transplantation of RPCs in eight patients with advanced retinitis pigmentosa. Patients were studied for 24 months. After RPC transplantation in RCS rats, we observed moderate recovery of vision and maintenance of the outer nuclear layer thickness. Most importantly, we did not find tumor formation or immune rejection. In the retinis pigmentosa patients given RPC injections, we also did not observe immunological rejection or tumorigenesis when immunosuppressive agents were not administered. We observed a significant improvement in visual acuity (P < 0.05) in five patients and an increase in retinal sensitivity of pupillary responses in three of the eight patients between 2 and 6 months after the transplant, but this improvement did not appear by 12 months. Our study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa. WHO Trial Registration, ChiCTR-TNRC-08000193 . Retrospectively registered on 5 December 2008.

Morphological remodeling of C. elegans neurons during aging is modified by compromised protein homeostasis

PubMed Central

Vayndorf, Elena M; Scerbak, Courtney; Hunter, Skyler; Neuswanger, Jason R; Toth, Marton; Parker, J Alex; Neri, Christian; Driscoll, Monica; Taylor, Barbara E

2016-01-01

Understanding cellular outcomes, such as neuronal remodeling, that are common to both healthy and diseased aging brains is essential to the development of successful brain aging strategies. Here, we used Caenorhabdits elegans to investigate how the expression of proteotoxic triggers, such as polyglutamine (polyQ)-expanded huntingtin and silencing of proteostasis regulators, such as the ubiquitin–proteasome system (UPS) and protein clearance components, may impact the morphological remodeling of individual neurons as animals age. We examined the effects of disrupted proteostasis on the integrity of neuronal cytoarchitecture by imaging a transgenic C. elegans strain in which touch receptor neurons express the first 57 amino acids of the human huntingtin (Htt) gene with expanded polyQs (128Q) and by using neuron-targeted RNA interference in adult wild-type neurons to knockdown genes encoding proteins involved in proteostasis. We found that proteostatic challenges conferred by polyQ-expanded Htt and knockdown of specific genes involved in protein homeostasis can lead to morphological changes that are restricted to specific domains of specific neurons. The age-associated branching of PLM neurons is suppressed by N-ter polyQ-expanded Htt expression, whereas ALM neurons with polyQ-expanded Htt accumulate extended outgrowths and other soma abnormalities. Furthermore, knockdown of genes important for ubiquitin-mediated degradation, lysosomal function, and autophagy modulated these age-related morphological changes in otherwise normal neurons. Our results show that the expression of misfolded proteins in neurodegenerative disease such as Huntington’s disease modifies the morphological remodeling that is normally associated with neuronal aging. Our results also show that morphological remodeling of healthy neurons during aging can be regulated by the UPS and other proteostasis pathways. Collectively, our data highlight a model in which morphological remodeling during

A retinal code for motion along the gravitational and body axes

PubMed Central

Sabbah, Shai; Gemmer, John A.; Bhatia-Lin, Ananya; Manoff, Gabrielle; Castro, Gabriel; Siegel, Jesse K.; Jeffery, Nathan; Berson, David M.

2017-01-01

Summary Self-motion triggers complementary visual and vestibular reflexes supporting image-stabilization and balance. Translation through space produces one global pattern of retinal image motion (optic flow), rotation another. We show that each subtype of direction-selective ganglion cell (DSGC) adjusts its direction preference topographically to align with specific translatory optic flow fields, creating a neural ensemble tuned for a specific direction of motion through space. Four cardinal translatory directions are represented, aligned with two axes of high adaptive relevance: the body and gravitational axes. One subtype maximizes its output when the mouse advances, others when it retreats, rises, or falls. ON-DSGCs and ON-OFF-DSGCs share the same spatial geometry but weight the four channels differently. Each subtype ensemble is also tuned for rotation. The relative activation of DSGC channels uniquely encodes every translation and rotation. Though retinal and vestibular systems both encode translatory and rotatory self-motion, their coordinate systems differ. PMID:28607486

Multimodality optical coherence tomography and fluorescence confocal scanning laser ophthalmoscopy in a zebrafish model of retinal vascular occlusion and remodeling

NASA Astrophysics Data System (ADS)

Li, Xiaoyue; Spitz, Kathleen; Bozic, Ivan; Tao, Yuankai K.

2018-02-01

Neovascularization in diabetic retinopathy (DR) and age-related macular degeneration (AMD) result in severe vision-loss and are two of the leading causes of blindness. The structural, metabolic, and vascular changes underlying retinal neovascularization are unknown and, thus, there is an unmet need to identify mechanisms of pathogenesis and novel anti-angiogenic therapies. Zebrafish is a robust ophthalmological model because its retina has comparable structure to the human retina and its fecundity and life-cycle enable development of mutant phenotypes of human pathologies. Here, we perform multimodal imaging with OCT and fluorescence confocal scanning laser ophthalmoscopy (cSLO) to identify changes in retinal structure and function in a zebrafish model of vascular leakage. Transgenic zebrafish with EGFP tagged plasma protein were imaged longitudinally at six time points over two weeks to visualize vascular perfusion changes from diethylaminobenzaldehyde (DEAB) treatment. Complementary contrast from OCT-A perfusion maps and cSLO imaging of plasma protein EGFP shows vascular occlusions posttreatment. cSLO images confirm presence of vessels despite loss of OCT-A signal. Plasma protein EGFP contrast also shows significant changes in vessel structure as compared to baseline images. OCT structural volumes show empty vessel cross-sections confirming non-perfusion. In addition, we present algorithms for automated biometric identification of OCT datasets using OCT-A vascular patterns in the presence of significant vascular perfusion changes. These results establish a framework for large-scale in vivo assays to identify novel anti-angiogenic compounds and understand the mechanisms ofneovascularization associated with retinal ocular pathologies.

TRPV2 Channels Contribute to Stretch-Activated Cation Currents and Myogenic Constriction in Retinal Arterioles.

PubMed

McGahon, Mary K; Fernández, José A; Dash, Durga P; McKee, Jon; Simpson, David A; Zholos, Alex V; McGeown, J Graham; Curtis, Tim M

2016-10-01

Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina. Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies. In some experiments, confocal immunolabeling of wholemount preparations was used to examine the localization of specific mechanosensitive TRP channels in retinal vascular smooth muscle cells (VSMCs). Reverse transcription-polymerase chain reaction analysis demonstrated mRNA expression for TRPC1, M7, V1, V2, V4, and P1, but not TRPC6 or M4, in isolated retinal arterioles. Immunolabeling revealed plasma membrane, cytosolic and nuclear expression of TRPC1, M7, V1, V2, V4, and P1 in retinal VSMCs. Hypoosmotic stretch-induced Ca2+ influx in retinal VSMCs was reversed by the TRPV2 inhibitor tranilast and the nonselective TRPP1/V2 antagonist amiloride. Inhibitors of TRPC1, M7, V1, and V4 had no effect. Hypoosmotic stretch-activated cation currents were similar in Na+ and Cs+ containing solutions suggesting no contribution by TRPP1 channels. Direct plasma membrane stretch triggered cation current activity that was blocked by tranilast and specific TRPV2 pore-blocking antibodies and mimicked by the TRPV2 activator, Δ9-tetrahydrocannabinol. Preincubation of retinal arterioles with TRPV2 blocking antibodies prevented the development of myogenic tone. Our results suggest that retinal VSMCs express a range of mechanosensitive TRP channels, but only TRPV2 appears to contribute to myogenic signaling in this vascular bed.

Identification of novel X-linked gain-of-function RPGR-ORF15 mutation in Italian family with retinitis pigmentosa and pathologic myopia

PubMed Central

Parmeggiani, Francesco; Barbaro, Vanessa; De Nadai, Katia; Lavezzo, Enrico; Toppo, Stefano; Chizzolini, Marzio; Palù, Giorgio; Parolin, Cristina; Di Iorio, Enzo

2016-01-01

The aim of this study was to describe a new pathogenic variant in the mutational hot spot exon ORF15 of retinitis pigmentosa GTPase regulator (RPGR) gene within an Italian family with X-linked retinitis pigmentosa (RP), detailing its distinctive genotype-phenotype correlation with pathologic myopia (PM). All members of this RP-PM family underwent a complete ophthalmic examination. The entire open reading frames of RPGR and retinitis pigmentosa 2 genes were analyzed by Sanger sequencing. A novel frame-shift mutation in exon ORF15 of RPGR gene (c.2091_2092insA; p.A697fs) was identified as hemizygous variant in the male proband with RP, and as heterozygous variant in the females of this pedigree who invariably exhibited symmetrical PM in both eyes. The c.2091_2092insA mutation coherently co-segregated with the observed phenotypes. These findings expand the spectrum of X-linked RP variants. Interestingly, focusing on Caucasian ethnicity, just three RPGR mutations are hitherto reported in RP-PM families: one of these is located in exon ORF15, but none appears to be characterized by a high penetrance of PM trait as observed in the present, relatively small, pedigree. The geno-phenotypic attributes of this heterozygosity suggest that gain-of-function mechanism could give rise to PM via a degenerative cell-cell remodeling of the retinal structures. PMID:27995965

Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation

PubMed Central

Phee, Hyewon; Au-Yeung, Byron B; Pryshchep, Olga; O'Hagan, Kyle Leonard; Fairbairn, Stephanie Grace; Radu, Maria; Kosoff, Rachelle; Mollenauer, Marianne; Cheng, Debra; Chernoff, Jonathan; Weiss, Arthur

2014-01-01

The molecular mechanisms that govern thymocyte development and maturation are incompletely understood. The P21-activated kinase 2 (Pak2) is an effector for the Rho family GTPases Rac and Cdc42 that regulate actin cytoskeletal remodeling, but its role in the immune system remains poorly understood. In this study, we show that T-cell specific deletion of Pak2 gene in mice resulted in severe T cell lymphopenia accompanied by marked defects in development, maturation, and egress of thymocytes. Pak2 was required for pre-TCR β-selection and positive selection. Surprisingly, Pak2 deficiency in CD4 single positive thymocytes prevented functional maturation and reduced expression of S1P1 and KLF2. Mechanistically, Pak2 is required for actin cytoskeletal remodeling triggered by TCR. Failure to induce proper actin cytoskeletal remodeling impaired PLCγ1 and Erk1/2 signaling in the absence of Pak2, uncovering the critical function of Pak2 as an essential regulator that governs the actin cytoskeleton-dependent signaling to ensure normal thymocyte development and maturation. DOI: http://dx.doi.org/10.7554/eLife.02270.001 PMID:24843022

Retinal pigmentary changes in chronic uveitis mimicking retinitis pigmentosa.

PubMed

Sevgi, D Damla; Davoudi, Samaneh; Comander, Jason; Sobrin, Lucia

2017-09-01

To present retinal pigmentary changes mimicking retinitis pigmentosa (RP) as a finding of advanced uveitis. We retrospectively reviewed charts of patients without a family history of inherited retinal degenerations who presented with retinal pigment changes and signs of past or present intraocular inflammation. Comprehensive eye examination including best-corrected visual acuity, slit-lamp examination and dilated fundus examination was performed on all patients in addition to color fundus photography, optical coherence tomography, fluorescein angiography (FA), and full-field electroretinogram testing. We identified five patients with ages ranging from 33 to 66 years, who presented with RP-like retinal pigmentary changes which were eventually attributed to longstanding uveitis. The changes were bilateral in three cases and unilateral in two cases. Four of five cases presented with active inflammation, and the remaining case showed evidence of active intraocular inflammation during follow-up. This study highlights the overlapping features of advanced uveitis and RP including the extensive pigmentary changes. Careful review of possible past uveitis history, detailed examination of signs of past or present inflammation and ancillary testing, with FA often being most helpful, are required for the correct diagnosis. This is important, because intervention can prevent further damage if the cause of the pigmentary changes is destructive inflammation.

Chronic retinal necrosis: cytomegalovirus necrotizing retinitis associated with panretinal vasculopathy in non-HIV patients.

PubMed

Schneider, Eric W; Elner, Susan G; van Kuijk, Frederik J; Goldberg, Naomi; Lieberman, Ronni M; Eliott, Dean; Johnson, Mark W

2013-10-01

To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction. Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens. Five non-HIV patients with granular necrotizing retinitis, vitritis, and severe occlusive vasculopathy were identified. Patient histories all suggested a basis for limited immune dysfunction including advanced age (n = 4), diabetes mellitus (n = 4), and noncytotoxic immunotherapy (n = 3). Diagnosis of CMV retinitis was delayed in all cases and patients received either no antiviral therapy (n = 2) or incorrect antiviral therapy (n = 3) for presumed herpes simplex/varicella zoster-related acute retinal necrosis. Retinitis subsequently regressed in all cases with introduction of systemic ganciclovir/valganciclovir (n = 5) and/or intravitreal foscarnet (n = 2). Four of five patients developed neovascularization because of extensive retinal ischemia. The clinical expression of CMV-associated retinopathy is strongly related to immune status. In patients with limited immune dysfunction, a mixed clinical picture of intraocular inflammation with panretinal occlusive vasculopathy, more characteristic of acute retinal necrosis, and peripheral slowly progressive granular retinitis, more characteristic of classic CMV retinitis, is observed. Recognition of this atypical clinical presentation, which the authors term chronic retinal necrosis, should prompt molecular testing for CMV to determine the appropriate antiviral therapy. Consideration should also be given to prophylactic panretinal photocoagulation in such eyes, given the high risk of neovascular complications.

Proteomic Profiling of Cigarette Smoke Induced Changes in Retinal Pigment Epithelium Cells.

PubMed

Merl-Pham, Juliane; Gruhn, Fabian; Hauck, Stefanie M

2016-01-01

Age-related macular degeneration (AMD) is a medical condition usually affecting older adults and resulting in a loss of vision in the macula, the center of the visual field. The dry form of this disease presents with atrophy of the retinal pigment epithelium, resulting in the detachment of the retina and loss of photoreceptors. Cigarette smoke is one main risk factor for dry AMD and increases the risk of developing the disease by three times. In order to understand the influence of cigarette smoke on retinal pigment epithelial cells, cultured human ARPE-19 cells were treated with cigarette smoke extract for 24 h. Using quantitative mass spectrometry more than 3000 proteins were identified and their respective abundances were compared between cigarette smoke-treated and untreated cells. Altogether 1932 proteins were quantified with at least two unique peptides, with 686 proteins found to be significantly differentially abundant with p > 0.05. Of these proteins the abundance of 64 proteins was at least 2-fold down-regulated after cigarette smoke treatment while 120 proteins were 2-fold up-regulated. The analysis of associated biological processes revealed an alteration of proteins involved in RNA processing and transport as well as extracellular matrix remodelling in response to cigarette smoke treatment.

The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons

PubMed Central

Miller-Fleming, Tyne W; Petersen, Sarah C; Manning, Laura; Matthewman, Cristina; Gornet, Megan; Beers, Allison; Hori, Sayaka; Mitani, Shohei; Bianchi, Laura; Richmond, Janet; Miller, David M

2016-01-01

Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a trigger in an activity-dependent mechanism that removes synapses in remodeling GABAergic neurons. UNC-8 cation channel activity promotes disassembly of presynaptic domains in DD type GABA neurons, but not in VD class GABA neurons where unc-8 expression is blocked by the COUP/TF transcription factor, UNC-55. We propose that the depolarizing effect of UNC-8-dependent sodium import elevates intracellular calcium in a positive feedback loop involving the voltage-gated calcium channel UNC-2 and the calcium-activated phosphatase TAX-6/calcineurin to initiate a caspase-dependent mechanism that disassembles the presynaptic apparatus. Thus, UNC-8 serves as a link between genetic and activity-dependent pathways that function together to promote the elimination of GABA synapses in remodeling neurons. DOI: http://dx.doi.org/10.7554/eLife.14599.001 PMID:27403890

Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats

PubMed Central

Roth, Steven; Dreixler, John C.; Mathew, Biji; Balyasnikova, Irina; Mann, Jacob R.; Boddapati, Venkat; Xue, Lai; Lesniak, Maciej S.

2016-01-01

Purpose We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina. Methods Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays. Results Eyes injected with hypoxic BMSC–conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium. Conclusions The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect. PMID:27367588

Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa

PubMed Central

Scott, Patrick A.; de Castro, Juan P. Fernandez; DeMarco, Paul J.; Ross, Jason W.; Njoka, Josephat; Walters, Eric; Prather, Randall S.; McCall, Maureen A.; Kaplan, Henry J.

2017-01-01

Purpose We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy. Methods The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age. Miniswine were euthanized and their retinas processed for morphologic evaluation at the light and electron microscopic level. Retinal morphology of a 36-month-old Tg miniswine also was examined. Results Wild type littermates reached mature scotopic and photopic retinal function by 3 months, while TgP23H miniswine showed abnormal scotopic ffERGs at the earliest time point, 1 month, and depressed photopic ffERGs after 2 months. Rod and cone photoreceptors (PR) exhibited morphologic abnormalities and dropout from the outer nuclear layer at 1 month, with only a monolayer of cone PR somata remaining after 2 months. The retinas showed progressive neural remodeling of the outer retina that included dendritic retraction of rod bipolar cells and glial seal formation by Müller cells. The TgP23H founder miniswine showed cone PR with relatively intact morphology exclusive to the area centralis. Conclusions The F1 Tg miniswine and the TgP23H founder miniswine exhibit similar retinopathy. Translational Relevance TgP23H miniswine are a useful large-eye model to study pathogenesis and preservation cone PRs in humans with retinitis pigmentosa. PMID:28316877

RETINAL DEEP CAPILLARY ISCHEMIA ASSOCIATED WITH AN OCCLUDED CONGENITAL RETINAL MACROVESSEL.

PubMed

Hasegawa, Taiji; Ogata, Nahoko

2017-01-01

To report the case of a patient with an occluded congenital retinal macrovessel accompanied by retinal deep capillary ischemia. A 38-year-old woman presented with a 2-day history of a paracentral scotoma of her right eye. Fundus photograph showed a dilated congenital retinal macrovessel with arteriovenous anastomosis, an intravascular white region indicating the thrombus at arteriovenous anastomotic region, and an area of retinal whitening temporal to the fovea. The spectral domain optical coherence tomography images through the area of retinal whitening showed a thickening and highly reflectivity at the level of the inner nuclear layer, which is likely due to the deep capillary ischemia. After 6 weeks, spectral domain optical coherence tomography images through the same area demonstrated a thinning and atrophy of only the inner nuclear layer, and the patient's paracentral scotoma persisted. Acute capillary hemodynamic changes caused deep capillary ischemia. The spectral domain optical coherence tomography showed a highly reflective lesion at the level of the inner nuclear layer in the acute phase.

The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β and TNF-α

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

Salles von-Held-Ventura, Juliana; Mázala-de-Oliveira, Thalita; Cândida da Rocha Oliveira, Amanda

Ouabain is a steroid hormone that binds to the enzyme Na{sup +}, K{sup +} – ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1β and TNF-α are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1β and TNF-α also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1β and TNF-α couldmore » be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1β or anti-TNF-α antibodies. In agreement, IL-1β or TNF-α increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-α and IL-1β from retinal cell cultures. Interestingly, TNF-α and IL-1β regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF-α and IL-1β signaling pathways leading to an increase in retinal ganglion cell survival. - Highlights: • Pro-inflammatory cytokines regulates the ouabain effect on RGC survival. • Ouabain treatment modulates the intracellular levels of TNF-α and IL-1β. • Ouabain induces the release of TNF-α and IL-1β in retinal cell cultures.« less

The potential roles of metallothionein as a therapeutic target for cerebral ischemia and retinal diseases.

PubMed

Ito, Yasushi; Tanaka, Hirotaka; Hara, Hideaki

2013-01-01

Methallothionein (MT) is a low molecular weight cysteine rich metalloprotein. In mammals, there are four isoforms (MT-1, -2, -3, and -4) and they have multiple roles, such as the detoxification of heavy metals, regulating essential metal homeostasis, and protecting against oxidative stress. Recently, accumulating studies have suggested that MTs (especially MT-1, -2, and -3) are an important neuroprotective substance for cerebral ischemia and retinal diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), that are characterized by a progressive retinal degeneration. Oxidative stress and/or zinc toxicity has been implicated as part of the common pathway in these diseases. Studying the expression patterns and functions of MTs may broaden our understanding of the endogenous molecular responses that these diseases trigger, and may help us to develop new therapeutic strategies to treat them. However, the precise roles of MTs within the brain and retina are not fully understood in terms of neuropathological conditions. In this review, we discuss the recent findings focusing on MTs' functions following cerebral ischemia, AMD, and RP.

MULTIMODAL IMAGING OF SYPHILITIC MULTIFOCAL RETINITIS.

PubMed

Curi, Andre L; Sarraf, David; Cunningham, Emmett T

2015-01-01

To describe multimodal imaging of syphilitic multifocal retinitis. Observational case series. Two patients developed multifocal retinitis after treatment of unrecognized syphilitic uveitis with systemic corticosteroids in the absence of appropriate antibiotic therapy. Multimodal imaging localized the foci of retinitis within the retina in contrast to superficial retinal precipitates that accumulate on the surface of the retina in eyes with untreated syphilitic uveitis. Although the retinitis resolved after treatment with systemic penicillin in both cases, vision remained poor in the patient with multifocal retinitis involving the macula. Treatment of unrecognized syphilitic uveitis with corticosteroids in the absence of antitreponemal treatment can lead to the development of multifocal retinitis. Multimodal imaging, and optical coherence tomography in particular, can be used to distinguish multifocal retinitis from superficial retinal precipitates or accumulations.

Spatiotemporal characteristics of retinal response to network-mediated photovoltaic stimulation.

PubMed

Ho, Elton; Smith, Richard; Goetz, Georges; Lei, Xin; Galambos, Ludwig; Kamins, Theodore I; Harris, James; Mathieson, Keith; Palanker, Daniel; Sher, Alexander

2018-02-01

Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor degeneration using electrical activation of the surviving inner retinal neurons. Today, such implants deliver visual information with low-frequency stimulation, resulting in discontinuous visual percepts. We measured retinal responses to complex visual stimuli delivered at video rate via a photovoltaic subretinal implant and by visible light. Using a multielectrode array to record from retinal ganglion cells (RGCs) in the healthy and degenerated rat retina ex vivo, we estimated their spatiotemporal properties from the spike-triggered average responses to photovoltaic binary white noise stimulus with 70-μm pixel size at 20-Hz frame rate. The average photovoltaic receptive field size was 194 ± 3 μm (mean ± SE), similar to that of visual responses (221 ± 4 μm), but response latency was significantly shorter with photovoltaic stimulation. Both visual and photovoltaic receptive fields had an opposing center-surround structure. In the healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This reversal is consistent with depolarization of photoreceptors by electrical pulses, as opposed to their hyperpolarization under increasing light, although alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF photovoltaic responses were observed, but in the absence of visual responses, it is not clear what functional RGC types they correspond to. Degenerate retina maintained the antagonistic center-surround organization of receptive fields. These fast and spatially localized network-mediated ON and OFF responses to subretinal stimulation via photovoltaic pixels with local return electrodes raise confidence in the possibility of providing more functional prosthetic vision. NEW & NOTEWORTHY Retinal prostheses currently in clinical use have struggled to deliver visual information at naturalistic frequencies, resulting in discontinuous percepts. We

Bilateral patching in retinal detachment: fluid mechanics and retinal "settling".

PubMed

Foster, William J

2011-07-20

When a patient suffers a retinal detachment and surgery is delayed, it is known clinically that bilaterally patching the patient may allow the retina to partially reattach or "settle." Although this procedure has been performed since the 1860s, there is still debate as to how such a maneuver facilitates the reattachment of the retina. Finite element calculations using commercially available analysis software are used to elucidate the influence of reduction in eye movement caused by bilateral patching on the flow of subretinal fluid in a physical model of retinal detachment. It was found that by coupling fluid mechanics with structural mechanics, a physically consistent explanation of increased retinal detachment with eye movements can be found in the case of traction on the retinal hole. Large eye movements increase vitreous traction and detachment forces on the edge of the retinal hole, creating a subretinal vacuum and facilitating increased subretinal fluid. Alternative models, in which intraocular fluid flow is redirected into the subretinal space, are not consistent with these simulations. The results of these simulations explain the physical principles behind bilateral patching and provide insight that can be used clinically. In particular, as is known clinically, bilateral patching may facilitate a decrease in the height of a retinal detachment. The results described here provide a description of a physical mechanism underlying this technique. The findings of this study may aid in deciding whether to bilaterally patch patients and in counseling patients on pre- and postoperative care.

Laser-induced retinal damage thresholds for annular retinal beam profiles

NASA Astrophysics Data System (ADS)

Kennedy, Paul K.; Zuclich, Joseph A.; Lund, David J.; Edsall, Peter R.; Till, Stephen; Stuck, Bruce E.; Hollins, Richard C.

2004-07-01

The dependence of retinal damage thresholds on laser spot size, for annular retinal beam profiles, was measured in vivo for 3 μs, 590 nm pulses from a flashlamp-pumped dye laser. Minimum Visible Lesion (MVL)ED50 thresholds in rhesus were measured for annular retinal beam profiles covering 5, 10, and 20 mrad of visual field; which correspond to outer beam diameters of roughly 70, 160, and 300 μm, respectively, on the primate retina. Annular beam profiles at the retinal plane were achieved using a telescopic imaging system, with the focal properties of the eye represented as an equivalent thin lens, and all annular beam profiles had a 37% central obscuration. As a check on experimental data, theoretical MVL-ED50 thresholds for annular beam exposures were calculated using the Thompson-Gerstman granular model of laser-induced thermal damage to the retina. Threshold calculations were performed for the three experimental beam diameters and for an intermediate case with an outer beam diameter of 230 μm. Results indicate that the threshold vs. spot size trends, for annular beams, are similar to the trends for top hat beams determined in a previous study; i.e., the threshold dose varies with the retinal image area for larger image sizes. The model correctly predicts the threshold vs. spot size trends seen in the biological data, for both annular and top hat retinal beam profiles.

Modern retinal laser therapy

PubMed Central

Kozak, Igor; Luttrull, Jeffrey K.

2014-01-01

Medicinal lasers are a standard source of light to produce retinal tissue photocoagulation to treat retinovascular disease. The Diabetic Retinopathy Study and the Early Treatment Diabetic Retinopathy Study were large randomized clinical trials that have shown beneficial effect of retinal laser photocoagulation in diabetic retinopathy and have dictated the standard of care for decades. However, current treatment protocols undergo modifications. Types of lasers used in treatment of retinal diseases include argon, diode, dye and multicolor lasers, micropulse lasers and lasers for photodynamic therapy. Delivery systems include contact lens slit-lamp laser delivery, indirect ophthalmocope based laser photocoagulation and camera based navigated retinal photocoagulation with retinal eye-tracking. Selective targeted photocoagulation could be a future alternative to panretinal photocoagulation. PMID:25892934

Mitochondrial Dysfunction in Retinal Diseases

PubMed Central

Barot, Megha; Gokulgandhi, Mitan R.; Mitra, Ashim K.

2015-01-01

The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases. PMID:21978133

Mitochondrial dysfunction in retinal diseases.

PubMed

Barot, Megha; Gokulgandhi, Mitan R; Mitra, Ashim K

2011-12-01

The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases.

Probing how initial retinal configuration controls photochemical dynamics in retinal proteins

NASA Astrophysics Data System (ADS)

Wand, A.; Rozin, R.; Eliash, T.; Friedman, N.; Jung, K. H.; Sheves, M.; Ruhman, S.

2013-03-01

The effects of the initial retinal configuration and the active isomerization coordinate on the photochemistry of retinal proteins (RPs) are assessed by comparing photochemical dynamics of two stable retinal ground state configurations (all-trans,15-anti vs. 13-cis,15-syn), within two RPs: Bacteriorhodopsin (BR) and Anabaena Sensory Rhodopsin (ASR). Hyperspectral pump-probe spectroscopy shows that photochemistry starting from 13-cis retinal in both proteins is 3-10 times faster than when started in the all-trans state, suggesting that the hastening is ubiquitous to microbial RPs, regardless of their different biological functions and origin. This may also relate to the known disparity of photochemical rates between microbial RPs and visual pigments. Importance and possible underlying mechanisms are discussed as well.

Intracellular Signalling in Retinal Ischemia

DTIC Science & Technology

1990-07-01

36) However, vascularization of the RPE is not known to occur in human diseases of photoreceptor degeneration, such as retinitis pigmentosa ...A.C. (1986) Retinitis pigmentosa and retinal neovascularization. Ophthalmology 91, 1599- 1603. Figure la: Control rat retina, 8 weeks of age, central...TITLE (Include Security Classification) Intracellular Signalling in Retinal Ischemia 12. PERSONAL AUTHOR(S) Burns, Margaret Sue; Bellhorn, Roy William

Bilateral rhegmatogenous retinal detachment due to unusual retinal degeneration in Down syndrome: A case report.

PubMed

Yonemoto, Yumiko; Morishita, Seita; Fukumoto, Masanori; Mimura, Masashi; Sato, Takaki; Kida, Teruyo; Kojima, Shota; Oku, Hidehiro; Sugasawa, Jun; Ikeda, Tsunehiko

2018-06-01

The aim of this study was to report a case of Down syndrome (DS) complicated with bilateral retinal detachment (RD) due to unusual retinal degeneration. A 9-year-old girl complained of bilateral visual disturbance during a follow-up examination for myopia and strabismus. Slit-lamp examination revealed moderate posterior subcapsular cataract in both eyes. B-mode echography showed bilateral bullous RD; however, it was difficult to detect the causal retinal breaks due to poor mydriasis. For treatment, the patient underwent bilateral lensectomy, vitrectomy, and silicone oil tamponade. Intraoperative findings revealed symmetrical retinal breaks and unusual caterpillar-like retinal degeneration on the upper temporal side of both eyes. Three months later, the patient underwent bilateral silicone oil removal and intraocular lens implantation. In this case, the retinal degeneration was morphologically different from retinal lattice degeneration, thus suggesting that it might be involved in the onset of DS-related bilateral RD.

Pan-retinal characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

PubMed Central

Hilgen, Gerrit; Pirmoradian, Sahar; Pamplona, Daniela; Kornprobst, Pierre; Cessac, Bruno; Hennig, Matthias H.; Sernagor, Evelyne

2017-01-01

We have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to different contrasts not only revealed a complex developmental profile for ON, OFF and ON-OFF responses, but also unveiled differences between dorsal and ventral RGC responses. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental profile of ON and OFF responses exhibited antagonistic behaviour, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive field (RF) center sizes decrease, spike-triggered averaged responses to white noise become stronger, and centers become more circular while maintaining differences between RGC types. We conclude that the maturation of retinal functionality is not spatially homogeneous, likely reflecting ecological requirements that favour earlier maturation of the dorsal retina. PMID:28186129

Overexpression of miR-183/-96/-182 triggers neuronal cell fate in Human Retinal Pigment Epithelial (hRPE) cells in culture.

PubMed

Davari, Maliheh; Soheili, Zahra-Soheila; Samiei, Shahram; Sharifi, Zohreh; Pirmardan, Ehsan Ranaei

2017-01-29

miR-183 cluster, composed of miR-183/-96/-182 genes, is highly expressed in the adult retina, particularly in photoreceptors. It involves in development, maturation and normal function of neuroretina. Ectopic overexpression of miR-183/-96/-182 genes was performed to assess reprogramming of hRPE cells. They were amplified from genomic DNA and cloned independently or in tandem configuration into pAAV.MCS vector. hRPE cells were then transfected with the recombinant constructs. Real-Time PCR was performed to measure the expression levels of miR-183/-96/-182 and that of several retina-specific neuronal genes such as OTX2, NRL, PDC and DCT. The transfected cells also were immunocytochemically examined for retina-specific neuronal markers, including Rhodopsin, red opsin, CRX, Thy1, CD73, recoverin and PKCα, to determine the cellular fate of the transfected hRPE cells. Data showed that upon miR-183/-96/-182 overexpression in hRPE cultures, the expression of neuronal genes including OTX2, NRL, PDC and DCT was also upregulated. Moreover, miR-183 cluster-treated hRPE cells were immunoreactive for neuronal markers such as Rhodopsin, red opsin, CRX and Thy1. Both transcriptional and translational upregulation of neuronal genes in miR-183 cluster-treated hRPE cells suggests that in vitro overexpression of miR-183 cluster could trigger reprogramming of hRPE cells to retinal neuron fate. Copyright © 2016 Elsevier Inc. All rights reserved.

Retinal vascular caliber and the development of hypertension: a meta-analysis of individual participant data.

PubMed

Ding, Jie; Wai, Khin Lay; McGeechan, Kevin; Ikram, M Kamran; Kawasaki, Ryo; Xie, Jing; Klein, Ronald; Klein, Barbara B K; Cotch, Mary Frances; Wang, Jie Jin; Mitchell, Paul; Shaw, Jonathan E; Takamasa, Kayama; Sharrett, A Richey; Wong, Tien Y

2014-02-01

Microvascular dysfunction has been suggested to be a major pathogenic factor for the development of hypertension. We examined the association between retinal vascular caliber, a marker of systemic microvascular dysfunction, and incident hypertension on a meta-analysis of individual participant data. We performed a systematic review with relevant studies identified through a search of electronic databases, a review of reference lists, and correspondence with experts. Studies were included if participants were selected from a general population, retinal vascular caliber was measured from photographs using computer-assisted methods at baseline, and individuals were followed up to ascertain the incidence of hypertension. Prespecified individual recorded data from six population-based prospective cohort studies were included. Discrete time proportional odds models were constructed for each study with adjustment for hypertension risk factors. Log odds ratios (ORs) per 20-μm difference were pooled using random-effects meta-analysis. Among 10 229 participants without prevalent hypertension, diabetes, or cardiovascular disease, 2599 developed new-onset hypertension during median follow-up periods ranging from 2.9 to 10 years. Both narrower retinal arterioles [pooled multivariate-adjusted OR per 20-μm difference 1.29, 95% confidence interval (CI) 1.20-1.39] and wider venules (OR per 20-μm difference 1.14, 95% CI 1.06-1.23) were associated with an increased risk of hypertension. Each 20 μm narrower arterioles at baseline were associated with a 1.12 mmHg (95% CI 0.25-1.99) greater increase in SBP over 5 years. Retinal arteriolar narrowing and venular widening were independently associated with an increased risk of hypertension. These findings underscore the importance of microvascular remodeling in the pathogenesis of hypertension.

Fundus autofluorescence and retinal structure as determined by spectral domain optical coherence tomography, and retinal function in retinitis pigmentosa.

PubMed

Iriyama, Aya; Yanagi, Yasuo

2012-03-01

To investigate the association between fundus autofluorescence (FAF) and retinal structure and function in retinitis pigmentosa (RP). For image acquisition, HRA2 (Heidelberg Engineering) and 3D-OCT1000 (Topcon Corp.) were used. Based on FAF examination, 88 eyes of 44 RP patients were categorized into three types. The area within the hyperautofluorescent ring and the area of preserved retinal autofluorescence with FAF was calculated. The association between the pattern of FAF and the residual area of the junction between the inner and outer segments of the photoreceptors (IS/OS line), and the relationship between the area within hyperautofluorescent ring, the area of preserved retinal autofluorescence and the mean deviation (MD) of static perimetry were assessed. Twenty-four eyes were with preserved retinal autofluorescence without hyperautofluorescent ring, 54 eyes were with hyperautofluorescent ring and ten eyes were with abnormal foveal autofluorescence both in the fovea and the periphery of the 30° scan. In the first type, the IS/OS line was clearly detected. In the second type, the residual area of the partially distinct IS/OS line corresponded with the area within hyperautofluorescent ring with significant correlation between the area within hyperautofluorescent ring and the MD (R(2) = 0.705, p < 0.001); however, there was no correlation between the area of preserved retinal autofluorescence and the MD, or between the area of preserved retinal autofluorescence and the area within hyperautofluorescent ring. In the third type, the IS/OS line was completely absent. The residual IS/OS line can be found in the area inside the hyperautofluorescent ring and correlates with residual visual function.

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment

PubMed Central

Lee, Christine; Tu, Hong Anh; Weir, Mark; Holubowich, Corinne

2016-01-01

Background Retinitis pigmentosa is a group of genetic disorders that involves the breakdown and loss of photoreceptors in the retina, resulting in progressive retinal degeneration and eventual blindness. The Argus II Retinal Prosthesis System is the only currently available surgical implantable device approved by Health Canada. It has been shown to improve visual function in patients with severe visual loss from advanced retinitis pigmentosa. The objective of this analysis was to examine the clinical effectiveness, cost-effectiveness, budget impact, and safety of the Argus II system in improving visual function, as well as exploring patient experiences with the system. Methods We performed a systematic search of the literature for studies examining the effects of the Argus II retinal prosthesis system in patients with advanced retinitis pigmentosa, and appraised the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria, focusing on visual function, functional outcomes, quality of life, and adverse events. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care over a 10-year time horizon. We also conducted a 5-year budget impact analysis. We used a qualitative design and an interview methodology to examine patients’ lived experience, and we used a modified grounded theory methodology to analyze information from interviews. Transcripts were coded, and themes were compared against one another. Results One multicentre international study and one single-centre study were included in the clinical review. In both studies, patients showed improved visual function with the Argus II system. However, the sight-threatening surgical complication rate was substantial. In the base-case analysis, the Argus II system was cost-effective compared with standard care only if willingness-to-pay was more than $207,616 per quality-adjusted life

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment.

PubMed

2016-01-01

Retinitis pigmentosa is a group of genetic disorders that involves the breakdown and loss of photoreceptors in the retina, resulting in progressive retinal degeneration and eventual blindness. The Argus II Retinal Prosthesis System is the only currently available surgical implantable device approved by Health Canada. It has been shown to improve visual function in patients with severe visual loss from advanced retinitis pigmentosa. The objective of this analysis was to examine the clinical effectiveness, cost-effectiveness, budget impact, and safety of the Argus II system in improving visual function, as well as exploring patient experiences with the system. We performed a systematic search of the literature for studies examining the effects of the Argus II retinal prosthesis system in patients with advanced retinitis pigmentosa, and appraised the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria, focusing on visual function, functional outcomes, quality of life, and adverse events. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care over a 10-year time horizon. We also conducted a 5-year budget impact analysis. We used a qualitative design and an interview methodology to examine patients' lived experience, and we used a modified grounded theory methodology to analyze information from interviews. Transcripts were coded, and themes were compared against one another. One multicentre international study and one single-centre study were included in the clinical review. In both studies, patients showed improved visual function with the Argus II system. However, the sight-threatening surgical complication rate was substantial. In the base-case analysis, the Argus II system was cost-effective compared with standard care only if willingness-to-pay was more than $207,616 per quality-adjusted life-year. The 5-year budget

Epigenetic remodelling and dysregulation of DLGAP4 is linked with early-onset cerebellar ataxia

PubMed Central

Minocherhomji, Sheroy; Hansen, Claus; Kim, Hyung-Goo; Mang, Yuan; Bak, Mads; Guldberg, Per; Papadopoulos, Nickolas; Eiberg, Hans; Doh, Gerald Dayebga; Møllgård, Kjeld; Hertz, Jens Michael; Nielsen, Jørgen E.; Ropers, Hans-Hilger; Tümer, Zeynep; Tommerup, Niels; Kalscheuer, Vera M.; Silahtaroglu, Asli

2014-01-01

Genome instability, epigenetic remodelling and structural chromosomal rearrangements are hallmarks of cancer. However, the coordinated epigenetic effects of constitutional chromosomal rearrangements that disrupt genes associated with congenital neurodevelopmental diseases are poorly understood. To understand the genetic–epigenetic interplay at breakpoints of chromosomal translocations disrupting CG-rich loci, we quantified epigenetic modifications at DLGAP4 (SAPAP4), a key post-synaptic density 95 (PSD95) associated gene, truncated by the chromosome translocation t(8;20)(p12;q11.23), co-segregating with cerebellar ataxia in a five-generation family. We report significant epigenetic remodelling of the DLGAP4 locus triggered by the t(8;20)(p12;q11.23) translocation and leading to dysregulation of DLGAP4 expression in affected carriers. Disruption of DLGAP4 results in monoallelic hypermethylation of the truncated DLGAP4 promoter CpG island. This induced hypermethylation is maintained in somatic cells of carriers across several generations in a t(8;20) dependent-manner however, is erased in the germ cells of the translocation carriers. Subsequently, chromatin remodelling of the locus-perturbed monoallelic expression of DLGAP4 mRNAs and non-coding RNAs in haploid cells having the translocation. Our results provide new mechanistic insight into the way a balanced chromosomal rearrangement associated with a neurodevelopmental disorder perturbs allele-specific epigenetic mechanisms at breakpoints leading to the deregulation of the truncated locus. PMID:24986922

Peripheral Retinal Vascular Patterns in Patients with Rhegmatogenous Retinal Detachment in Taiwan

PubMed Central

Chen, San-Ni; Hwang, Jiunn-Feng; Wu, Wen-Chuan

2016-01-01

This is an observational study of fluorescein angiography (FA) in consecutive patients with rhegmatogenous retinal detachment (RRD) in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL), and refraction status (RF) recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8%) in group 1, 3 eyes (4.1%) in group 2, 40 eyes (54.8%) in group 3 and 17 eyes (23.3%) in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion. PMID:26909812

Genetics Home Reference: retinitis pigmentosa

MedlinePlus

... Email Facebook Twitter Home Health Conditions Retinitis pigmentosa Retinitis pigmentosa Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Retinitis pigmentosa is a group of related eye disorders that ...

Repair of Traumatic Rhegmatogenous Retinal Detachment Combined with Congenital Falciform Retinal Detachment.

PubMed

Mano, Fukutaro; Chang, Kuo-Chung; Mano, Tomiya

2018-01-01

To report a case of surgical repair of traumatic rhegmatogenous retinal detachment combined with congenital falciform retinal detachment (FRD). A retrospective case report. A 36-year-old man with traumatic rhegmatogenous retinal detachment complicating a previously known FRD was successfully treated despite residual FRD following pars plana lensectomy, vitrectomy, and encircling scleral buckling. His best corrected visual acuity improved from hand motion at 50 cm to 20/1,000. We concluded that the root of the FRD is susceptible to trauma because of the contraction of fibrovascular tissue. The early intervention of modern vitrectomy to traumatic rhegmatogenous retinal detachment complicating a previously known FRD is an important consideration for enhanced quality of care and optimal patient outcomes.

Electrotonic remodeling following myocardial infarction in dogs susceptible and resistant to sudden cardiac death.

PubMed

Del Rio, Carlos L; McConnell, Patrick I; Kukielka, Monica; Dzwonczyk, Roger; Clymer, Bradley D; Howie, Michael B; Billman, George E

2008-02-01

Passive electrical remodeling following myocardial infarction (MI) is well established. These changes can alter electrotonic loading and trigger the remodeling of repolarization currents, a potential mechanism for ventricular fibrillation (VF). However, little is known about the role of passive electrical markers as tools to identify VF susceptibility post-MI. This study investigated electrotonic remodeling in the post-MI ventricle, as measured by myocardial electrical impedance (MEI), in animals prone to and resistant to VF. MI was induced in dogs by a two-stage left anterior descending (LAD) coronary artery ligation. Before infarction, MEI electrodes were placed in remote (left circumflex, LCX) and infarcted (LAD) myocardium. MEI was measured in awake animals 1, 2, 7, and 21 days post-MI. Subsequently, VF susceptibility was tested by a 2-min LCX occlusion during exercise; 12 animals developed VF (susceptible, S) and 12 did not (resistant, R). The healing infarct had lower MEI than the normal myocardium. This difference was stable by day 2 post-MI (287 +/- 32 Omega vs. 425 +/- 62 Omega, P < 0.05). Significant differences were observed between resistant and susceptible animals 7 days post-MI; susceptible dogs had a wider electrotonic gradient between remote and infarcted myocardium (R: 89 +/- 60 Omega vs. S: 180 +/- 37 Omega). This difference increased over time in susceptible animals (252 +/- 53 Omega at 21 days) due to post-MI impedance changes on the remote myocardium. These data suggest that early electrotonic changes post-MI could be used to assess later arrhythmia susceptibility. In addition, passive-electrical changes could be a mechanism driving active-electrical remodeling post-MI, thereby facilitating the induction of arrhythmias.

ADULT WITH CHICKENPOX COMPLICATED BY SYSTEMIC VASCULITIS AND BILATERAL RETINAL VASCULITIS WITH RETINAL VASCULAR OCCLUSIONS.

PubMed

Murdock, Jennifer; Carvounis, Petros E

2017-01-01

To describe an adult with chickenpox resulting in systemic vasculitis and bilateral retinal vascular occlusions. Single case report. A 58-year-old man with chickenpox complicated by disseminated varicella-zoster systemic and retinal vasculitis resulting in a combined arterial and venous occlusion in one eye with multiple branch retinal vein occlusions in the other eye. There was no evidence of retinitis. The patient systemically improved after treatment with acyclovir and steroids; however, his vision remained poor. Chickenpox can be associated with systemic vasculopathy and may rarely result in multiple systemic and ocular infarcts, including severe retinal vascular occlusions.

Investigation of Retinal Morphology Alterations Using Spectral Domain Optical Coherence Tomography in a Mouse Model of Retinal Branch and Central Retinal Vein Occlusion

PubMed Central

Ebneter, Andreas; Agca, Cavit; Dysli, Chantal; Zinkernagel, Martin S.

2015-01-01

Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions. PMID:25775456

Orthogonal decomposition of left ventricular remodeling in myocardial infarction.

PubMed

Zhang, Xingyu; Medrano-Gracia, Pau; Ambale-Venkatesh, Bharath; Bluemke, David A; Cowan, Brett R; Finn, J Paul; Kadish, Alan H; Lee, Daniel C; Lima, Joao A C; Young, Alistair A; Suinesiaputra, Avan

2017-03-01

Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices. Six clinical remodeling indices (end-diastolic volume index, sphericity, relative wall thickness, ejection fraction, apical conicity, and longitudinal shortening) were evaluated using cardiac magnetic resonance images of 300 patients with myocardial infarction, and 1991 asymptomatic subjects, obtained from the Cardiac Atlas Project. Partial least squares (PLS) regression of left ventricular shape models resulted in remodeling components that were optimally associated with each remodeling index. A Gram-Schmidt orthogonalization process, by which remodeling components were successively removed from the shape space in the order of shape variance explained, resulted in a set of orthonormal remodeling components. Remodeling scores could then be calculated that quantify the amount of each remodeling component present in each case. A one-factor PLS regression led to more decoupling between scores from the different remodeling components across the entire cohort, and zero correlation between clinical indices and subsequent scores. The PLS orthogonal remodeling components had similar power to describe differences between myocardial infarction patients and asymptomatic subjects as principal component analysis, but were better associated with well-understood clinical indices of cardiac remodeling. The data and analyses are available from www.cardiacatlas.org. © The Author 2017. Published by Oxford University Press.

Orthogonal decomposition of left ventricular remodeling in myocardial infarction

PubMed Central

Zhang, Xingyu; Medrano-Gracia, Pau; Ambale-Venkatesh, Bharath; Bluemke, David A.; Cowan, Brett R; Finn, J. Paul; Kadish, Alan H.; Lee, Daniel C.; Lima, Joao A. C.; Young, Alistair A.; Suinesiaputra, Avan

2017-01-01

Abstract Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices. Results: Six clinical remodeling indices (end-diastolic volume index, sphericity, relative wall thickness, ejection fraction, apical conicity, and longitudinal shortening) were evaluated using cardiac magnetic resonance images of 300 patients with myocardial infarction, and 1991 asymptomatic subjects, obtained from the Cardiac Atlas Project. Partial least squares (PLS) regression of left ventricular shape models resulted in remodeling components that were optimally associated with each remodeling index. A Gram–Schmidt orthogonalization process, by which remodeling components were successively removed from the shape space in the order of shape variance explained, resulted in a set of orthonormal remodeling components. Remodeling scores could then be calculated that quantify the amount of each remodeling component present in each case. A one-factor PLS regression led to more decoupling between scores from the different remodeling components across the entire cohort, and zero correlation between clinical indices and subsequent scores. Conclusions: The PLS orthogonal remodeling components had similar power to describe differences between myocardial infarction patients and asymptomatic subjects as principal component analysis, but were better associated with well-understood clinical indices of cardiac remodeling. The data and analyses are available from www.cardiacatlas.org. PMID:28327972

[Cytomegalovirus retinitis in immunocompetent patients].

PubMed

Yoshinaga, Wakako; Mizushima, Yuka; Abematsu, Noriko; Nakao, Kumiko; Sakamoto, Taiji

2008-08-01

Cytomegalovirus (CMV) retinitis usually affects severely immunosuppressed individuals. We report two immunocompetent patients who developed CMV retinitis. Case 1 was a 65-year-old man who was referred to us with blurred vision and floaters of 2 weeks duration in his left eye. Slit-lamp biomicroscopy showed keratic precipitates, aqueous cells, and vitreous opacity in his left eye. Funduscopic examination revealed yellow-white retinal lesions with arterial sheathing in the superotemporal midperiphery. Case 2 was a 63-year-old man who presented with a 2-week history of blurred vision in his left eye. Ophthalmologic examination of the left eye showed keratic precipitates, aqueous cells, vitreous opacity, and yellow-white lesions in the superotemporal peripheral retina. In both cases, CMV DNA was detected in the aqueous humor and therefore the diagnosis was CMV retinitis. CMV retinitis in both cases was indolent and was resolved in one month without treatment with antiviral drugs. Although both patients had diabetes mellitus, the results of their laboratory examinations were unremarkable and they were immunocompetent. Unlike CMV retinitis in immunocompromised patients, CMV retinitis in immunocompetent patients had significant anterior and vitreous inflammation but did not require antiviral treatment. A possible association between CMV retinitis and diabetes mellitus was suggested.

Retinal imaging and image analysis.

PubMed

Abràmoff, Michael D; Garvin, Mona K; Sonka, Milan

2010-01-01

Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships.

Retinal Imaging and Image Analysis

PubMed Central

Abràmoff, Michael D.; Garvin, Mona K.; Sonka, Milan

2011-01-01

Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships. PMID:22275207

Repair of Traumatic Rhegmatogenous Retinal Detachment Combined with Congenital Falciform Retinal Detachment

PubMed Central

Mano, Fukutaro; Chang, Kuo-Chung; Mano, Tomiya

2018-01-01

Purpose To report a case of surgical repair of traumatic rhegmatogenous retinal detachment combined with congenital falciform retinal detachment (FRD). Methods A retrospective case report. Results A 36-year-old man with traumatic rhegmatogenous retinal detachment complicating a previously known FRD was successfully treated despite residual FRD following pars plana lensectomy, vitrectomy, and encircling scleral buckling. His best corrected visual acuity improved from hand motion at 50 cm to 20/1,000. Conclusion We concluded that the root of the FRD is susceptible to trauma because of the contraction of fibrovascular tissue. The early intervention of modern vitrectomy to traumatic rhegmatogenous retinal detachment complicating a previously known FRD is an important consideration for enhanced quality of care and optimal patient outcomes. PMID:29643782

Color Doppler imaging of retinal diseases.

PubMed

Dimitrova, Galina; Kato, Satoshi

2010-01-01

Color Doppler imaging (CDI) is a widely used method for evaluating ocular circulation that has been used in a number of studies on retinal diseases. CDI assesses blood velocity parameters by using ultrasound waves. In ophthalmology, these assessments are mainly performed on the retrobulbar blood vessels: the ophthalmic, the central retinal, and the short posterior ciliary arteries. In this review, we discuss CDI use for the assessment of retinal diseases classified into the following: vascular diseases, degenerations, dystrophies, and detachment. The retinal vascular diseases that have been investigated by CDI include diabetic retinopathy, retinal vein occlusions, retinal artery occlusions, ocular ischemic conditions, and retinopathy of prematurity. Degenerations and dystrophies included in this review are age-related macular degeneration, myopia, and retinitis pigmentosa. CDI has been used for the differential diagnosis of retinal detachment, as well as the evaluation of retrobulbar circulation in this condition. CDI is valuable for research and is a potentially useful diagnostic tool in the clinical setting.

Panoramic autofluorescence: highlighting retinal pathology.

PubMed

Slotnick, Samantha; Sherman, Jerome

2012-05-01

Recent technological advances in fundus autofluorescence (FAF) are providing new opportunities for insight into retinal physiology and pathophysiology. FAF provides distinctly different imaging information than standard photography or color separation. A review of the basis for this imaging technology is included to help the clinician understand how to interpret FAF images. Cases are presented to illustrate image interpretation. Optos, which manufactures equipment for simultaneous panoramic imaging, has recently outfitted several units with AF capabilities. Six cases are presented in which panoramic autofluorescent (PAF) images highlight retinal pathology, using Optos' Ultra-Widefield technology. Supportive imaging technologies, such as Optomap® images and spectral domain optical coherence tomography (SD-OCT), are used to assist in the clinical interpretation of retinal pathology detected on PAF. Hypofluorescent regions on FAF are identified to occur along with a disruption in the photoreceptors and/or retinal pigment epithelium, as borne out on SD-OCT. Hyperfluorescent regions on FAF occur at the advancing zones of retinal degeneration, indicating impending damage. PAF enables such inferences to be made in retinal areas which lie beyond the reach of SD-OCT imaging. PAF also enhances clinical pattern recognition over a large area and in comparison with the fellow eye. Symmetric retinal degenerations often occur with genetic conditions, such as retinitis pigmentosa, and may impel the clinician to recommend genetic testing. Autofluorescent ophthalmoscopy is a non-invasive procedure that can detect changes in metabolic activity at the retinal pigment epithelium before clinical ophthalmoscopy. Already, AF is being used as an adjunct technology to fluorescein angiography in cases of age-related macular degeneration. Both hyper- and hypoautofluorescent changes are indicative of pathology. Peripheral retinal abnormalities may precede central retinal impacts, potentially

WIDEFIELD SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING OF PERIPHERAL ROUND RETINAL HOLES WITH OR WITHOUT RETINAL DETACHMENT.

PubMed

Casswell, Edward J; Abou Ltaif, Sleiman; Carr, Thomas; Keane, Pearse A; Charteris, David G; Wickham, Louisa

2018-03-02

To describe the widefield spectral-domain optical coherence tomography features of peripheral round retinal holes, with or without associated retinal detachment (RD). Retrospective, observational study of 28 eyes with peripheral round retinal holes, with and without RD. Patients underwent imaging with a widefield 50-degree spectral-domain optical coherence tomography (Heidelberg Engineering, Germany) and Optos ultra-widefield imaging systems (Optos, United Kingdom). Vitreous attachment at the site of the retinal hole was detected in 27/28 (96.4%) cases. Cases were split into three groups: RHs with RD (n = 12); RHs with subretinal fluid (n = 5), and flat RHs (n = 11), with minimal or no subretinal fluid. 91.6% retinal holes associated with subretinal fluid or RD had vitreous attachment at the site of the hole. Eighty percent had vitreous attachment at both edges of the retinal hole, in a U-shape configuration, which appeared to exert traction. By contrast, flat retinal holes had visible vitreous attachment only at one edge of the retinal hole in 45.4%. Vitreous attachment was commonly seen at the site of round retinal holes. Vitreous attachment at both edges of the retinal hole in a U-shape configuration was more commonly seen at holes associated with subretinal fluid or RD.

Evidence that ganglion cells react to retinal detachment.

PubMed

Coblentz, Francie E; Radeke, Monte J; Lewis, Geoffrey P; Fisher, Steven K

2003-03-01

Growth associated protein 43 (GAP 43) is involved in synapse formation and it is expressed in the retina in a very specific pattern. Although GAP 43 is downregulated at the time of synapse formation, it can be re-expressed following injury such as axotomy or ischemia. Because of this we sought to characterize the expression of GAP 43 after retinal detachment (RD). Immunoblot, immunocytochemical and quantitative polymerase chain reaction (QPCR) techniques were used to assess the level of GAP 43 expression after experimental RD. GAP 43 was localized to three sublaminae of the inner plexiform layer of the normal retina. GAP 43 became upregulated in a subset of retinal ganglion cells following at least 7 days of RD. By immunoblot GAP 43 could be detected by 3 days. QPCR shows the upregulation of GAP 43 message by 6hr of detachment. To further characterize changes in ganglion cells, we used an antibody to neurofilament 70 and 200kDa (NF) proteins. Anti-NF labels horizontal cells, ganglion cell dendrites in the inner plexiform layer, and ganglion cell axons (fasicles) in the normal retina. Following detachment it is upregulated in horizontal cells and ganglion cells. When detached retina was double labelled with anti-GAP 43 and anti-NF, some cells were labelled with both markers, while others labelled with only one. We have previously shown that second order neurons respond to detachment; here we show that third order neurons are responding as well. Cellular remodelling of this type in response to detachment may explain the slow recovery of vision that often occurs after reattachment, or those changes that are often assumed to be permanent.

Retinal O-linked N-acetylglucosamine protein modifications: implications for postnatal retinal vascularization and the pathogenesis of diabetic retinopathy

PubMed Central

Sieg, Kelsey M.; Shallow, Keegan D.; Sorenson, Christine M.; Sheibani, Nader

2013-01-01

Purpose Hyperglycemia activates several metabolic pathways, including the hexosamine biosynthetic pathway. Uridine diphosphate N-acetylglucosamine (GlcNAc) is the product of the hexosamine biosynthetic pathway and the substrate for O-linked GlcNAc (O-GlcNAc) modification. This modification affects a wide range of proteins by altering their activity, cellular localization, and/or protein interactions. However, the role O-GlcNAcylation may play in normal postnatal retinal vascular development and in the ocular complications of diabetes, including diabetic retinopathy, requires further investigation. Methods The total levels of O-GlcNAc-modified proteins were evaluated by western blot analysis of lysates prepared from retinas obtained at different days during postnatal retinal vascularization and oxygen-induced ischemic retinopathy. Similar experiments were performed with retinal lysate prepared from diabetic Ins2Akita/+ mice with different durations of diabetes and retinal vascular cells cultured under various glucose conditions. The localization of O-GlcNAc-modified proteins in the retinal vasculature was confirmed by immunofluorescence staining. The impact of altered O-GlcNAcylation on the migration of retinal vascular cells was determined using scratch wound and transwell migration assays. Results We detected an increase in protein O-GlcNAcylation during mouse postnatal retinal vascularization and aging, in part through the regulation of the enzymes that control this modification. The study of the diabetic Ins2Akita/+ mouse retina showed an increase in the O-GlcNAc modification of retinal proteins. We also observed an increase in retinal O-GlcNAcylated protein levels during the neovascularization phase of oxygen-induced ischemic retinopathy. Our fluorescence microscopy data confirmed that the alterations in retinal O-GlcNAcylation are similarly represented in the retinal vasculature and in retinal pericytes and endothelial cells. Particularly, the migration of

To Remodel or To Build?

ERIC Educational Resources Information Center

Rosenblum, Todd

2009-01-01

The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

Retinal detachment following endophthalmitis.

PubMed

Nelsen, P T; Marcus, D A; Bovino, J A

1985-08-01

Fifty-five consecutive patients with a clinical diagnosis of bacterial endophthalmitis were reviewed. All patients were treated with systemic, periocular, topical, and intravitreal antibiotics. In addition, 33 of the patients underwent a pars plana vitrectomy. Nine retinal detachments occurred within six months of initial diagnosis. The higher frequency of retinal detachment in the vitrectomy group (21%) as compared to those patients managed without vitrectomy (9%) may be explained by a combination of surgical complications and the increased severity of endophthalmitis in the vitrectomy group. The two patients who developed retinal detachment during vitrectomy surgery rapidly progressed to no light perception. Conversely, the repair of retinal detachments diagnosed postoperatively had a good prognosis.

Effect of pharmacologically induced retinal degeneration on retinal autofluorescence lifetimes in mice.

PubMed

Dysli, Chantal; Dysli, Muriel; Zinkernagel, Martin S; Enzmann, Volker

2016-12-01

Fluorescence lifetime imaging ophthalmoscopy (FLIO) was used to investigate retinal autofluorescence lifetimes in mouse models of pharmacologically induced retinal degeneration over time. Sodium iodate (NaIO 3 , 35 mg/kg intravenously) was used to induce retinal pigment epithelium (RPE) degeneration with subsequent loss of photoreceptors (PR) whereas N-methyl-N-nitrosourea (MNU, 45 mg/kg intraperitoneally) was employed for degeneration of the photoreceptor cell layer alone. All mice were measured at day 3, 7, 14, and 28 after the respective injection of NaIO 3 , MNU or NaCl (control). Fluorescence lifetime imaging was performed using a fluorescence lifetime imaging ophthalmoscope (Heidelberg Engineering, Heidelberg, Germany). Fluorescence was excited at 473 nm and fluorescence lifetimes were measured in a short and a long spectral channel (498-560 nm and 560-720 nm). Corresponding optical coherence tomography (OCT) images were consecutively acquired and histology was performed at the end of the experiments. Segmentation of OCT images and histology verified the cell type-specific degeneration process over time. Retinal autofluorescence lifetimes increased from day 3 to day 28 in mice after NaIO 3 treatment. Finally, at day 28, fluorescence lifetimes were prolonged by 8% in the short and 61% in the long spectral channel compared to control animals (p = 0.21 and p = 0.004, respectively). In mice after MNU treatment, the mean retinal autofluorescence lifetimes were already decreased at day 3 and retinal lifetimes were finally shortened by 27% in the short and 51% in the long spectral channel at day 28 (p = 0.0028). In conclusion, degeneration of the RPE with subsequent photoreceptor degeneration by NaIO 3 lead to longer mean fluorescence lifetimes of the retina compared to control mice, whereas during specific degeneration of the photoreceptor layer induced by MNU shorter lifetimes were measured. Therefore, short retinal fluorescence lifetimes may originate

Retinal patching: a new approach to the management of selected retinal breaks.

PubMed

Gilbert, C E; Grierson, I; McLeod, D

1989-01-01

Restoration of retinal continuity by a patching technique is proposed as a new means of treating selected rhegmatogenous retinal detachments where established techniques frequently fail. The patch consists of a substrate and adhesive applied to the inner surface of the retina surrounding the retinal break. Bovine eye cup experiments have been performed to explore the effectiveness of a range of adhesives, and cyanoacrylates and Tisseel have been found to be effective. Studies of these adhesives on confluent cultures of bovine retinal pigment epithelial cells and glia revealed temporary cyanoacrylate toxicity and stimulation of proliferation by Tisseel. Substrate biocompatability was investigated by observing the growth of cells on various substrates in tissue culture; biological substrates such as lens capsule supported cell growth whereas synthetic membranes only did so if pretreated with fibronectin.

A High Serum Iron Level Causes Mouse Retinal Iron Accumulation Despite an Intact Blood-Retinal Barrier

PubMed Central

Zhao, Liangliang; Li, Yafeng; Song, Delu; Song, Ying; Theurl, Milan; Wang, Chenguang; Cwanger, Alyssa; Su, Guanfang; Dunaief, Joshua L.

2015-01-01

The retina can be shielded by the blood-retinal barrier. Because photoreceptors are damaged by excess iron, it is important to understand whether the blood-retinal barrier protects against high serum iron levels. Bone morphogenic protein 6 (Bmp6) knockout mice have serum iron overload. Herein, we tested whether the previously documented retinal iron accumulation in Bmp6 knockout mice might result from the high serum iron levels or, alternatively, low levels of retinal hepcidin, an iron regulatory hormone whose transcription can be up-regulated by Bmp6. Furthermore, to determine whether increases in serum iron can elevate retinal iron levels, we i.v. injected iron into wild-type mice. Retinas were analyzed by real-time quantitative PCR and immunofluorescence to assess the levels of iron-regulated genes/proteins and oxidative stress. Retinal hepcidin mRNA levels in Bmp6 knockout retinas were the same as, or greater than, those in age-matched wild-type retinas, indicating that Bmp6 knockout does not cause retinal hepcidin deficiency. Changes in mRNA levels of L ferritin and transferrin receptor indicated increased retinal iron levels in i.v. iron-injected wild-type mice. Oxidative stress markers were elevated in photoreceptors of mice receiving i.v. iron. These findings suggest that elevated serum iron levels can overwhelm local retinal iron regulatory mechanisms. PMID:25174877

The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture.

PubMed

Cunha-Vaz, José

2017-01-01

Retinal diseases are the main causes of blindness in the Western world. Diabetic retinopathy and age-related macular degeneration continue to increase in prevalence and as main causes of vision loss. Intravitreal anti-VEGF and steroid injections have raised new expectations for their successful treatment. These agents act by stabilizing the blood-retinal barrier (BRB). Our group defined the BRB by identifying for the first time the tight junctions that unite retinal endothelial cells and are the basis for the inner BRB, an observation later confirmed in retinal pigment epithelial cells and in brain vessels. A major role of active transport processes was also identified. Today, the BRB is understood to play a fundamental role in retinal function in both health and disease. Retinal edema, an ubiquitous manifestation of retinal disease, is directly associated with breakdown of the BRB and with vision loss. In its most common form (i.e., vasogenic edema), due to breakdown of the BRB, Starling's law of capillary filtration may be used to interpret the mechanisms of fluid accumulation in the retina. The main factors involved in the development of retinal edema are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. In the clinical environment, breakdown of the BRB has been identified by fluorescein angiography and vitreous fluorometry, requiring the intravenous administration of fluorescein. An OCT-based method, OCT-Leakage, recently introduced by our group is capable of noninvasively identifying and quantifying sites of alteration of the BRB by mapping areas of lower-than-normal optical reflectivity, thus reflecting changes in the retinal extracellular fluid. We found good correspondence between the location of increased areas of low optical reflectivity identified by OCT-Leakage and the main sites of leakage on fluorescein angiography. Furthermore, with OCT-Leakage the areas of abnormal

Epigenomic regulation of oncogenesis by chromatin remodeling.

PubMed

Kumar, R; Li, D-Q; Müller, S; Knapp, S

2016-08-25

Disruption of the intricate gene expression program represents one of major driving factors for the development, progression and maintenance of human cancer, and is often associated with acquired therapeutic resistance. At the molecular level, cancerous phenotypes are the outcome of cellular functions of critical genes, regulatory interactions of histones and chromatin remodeling complexes in response to dynamic and persistent upstream signals. A large body of genetic and biochemical evidence suggests that the chromatin remodelers integrate the extracellular and cytoplasmic signals to control gene activity. Consequently, widespread dysregulation of chromatin remodelers and the resulting inappropriate expression of regulatory genes, together, lead to oncogenesis. We summarize the recent developments and current state of the dysregulation of the chromatin remodeling components as the driving mechanism underlying the growth and progression of human tumors. Because chromatin remodelers, modifying enzymes and protein-protein interactions participate in interpreting the epigenetic code, selective chromatin remodelers and bromodomains have emerged as new frontiers for pharmacological intervention to develop future anti-cancer strategies to be used either as single-agent or in combination therapies with chemotherapeutics or radiotherapy.

Dysfunction of outer segment guanylate cyclase caused by retinal disease related mutations

PubMed Central

Zägel, Patrick; Koch, Karl-Wilhelm

2014-01-01

Membrane bound guanylate cyclases are expressed in rod and cone cells of the vertebrate retina and mutations in several domains of rod outer segment guanylate cyclase 1 (ROS-GC1 encoded by the gene GUCY2D) correlate with different forms of retinal degenerations. In the present work we investigated the biochemical consequences of three point mutations, one is located in position P575L in the juxtamembrane domain close to the kinase homology domain and two are located in the cyclase catalytic domain at H1019P and P1069R. These mutations correlate with various retinal diseases like autosomal dominant progressive cone degeneration, e.g., Leber Congenital Amaurosis and a juvenile form of retinitis pigmentosa. Wildtype and mutant forms of ROS-GC1 were heterologously expressed in HEK cells, their cellular distribution was investigated and activity profiles in the presence and absence of guanylate cyclase-activating proteins were measured. The mutant P575L was active under all tested conditions, but it displayed a twofold shift in the Ca2+-sensitivity, whereas the mutant P1069R remained inactive despite normal expression levels. The mutation H1019P caused the cyclase to become more labile. The different biochemical consequences of these mutations seem to reflect the different clinical symptoms. The mutation P575L induces a dysregulation of the Ca2+-sensitive cyclase activation profile causing a slow progression of the disease by the distortion of the Ca2+-cGMP homeostasis. In contrast, a strong reduction in cGMP synthesis due to an inactive or structurally unstable ROS-GC1 would trigger more severe forms of retinal diseases. PMID:24616660

Sector retinitis pigmentosa.

PubMed

Van Woerkom, Craig; Ferrucci, Steven

2005-05-01

Retinitis pigmentosa (RP) is one of the most common hereditary retinal dystrophies and causes of visual impairment affecting all age groups. The reported incidence varies, but is considered to be between 1 in 3,000 to 1 in 7,000. Sector retinitis pigmentosa is an atypical form of RP that is characterized by regionalized areas of bone spicule pigmentation, usually in the inferior quadrants of the retina. A 57-year-old Hispanic man with a history of previously diagnosed retinitis pigmentosa came to the clinic with a longstanding symptom of decreased vision at night. Bone spicule pigmentation was found in the nasal and inferior quadrants in each eye. He demonstrated superior and temporal visual-field loss corresponding to the areas of the affected retina. Clinical measurements of visual-field loss, best-corrected visual acuity, and ophthalmoscopic appearance have remained stable during the five years the patient has been followed. Sector retinitis pigmentosa is an atypical form of RP that is characterized by bilateral pigmentary retinopathy, usually isolated to the inferior quadrants. The remainder of the retina appears clinically normal, although studies have found functional abnormalities in these areas as well. Sector RP is generally considered a stationary to slowly progressive disease, with subnormal electro-retinogram findings and visual-field defects corresponding to the involved retinal sectors. Management of RP is very difficult because there are no proven methods of treatment. Studies have shown 15,000 IU of vitamin A palmitate per day may slow the progression, though this result is controversial. Low vision rehabilitation, long wavelength pass filters, and pedigree counseling remain the mainstay of management.

Characteristics of eyes with inner retinal cleavage.

PubMed

Hwang, Young Hoon; Kim, Yong Yeon; Kim, Hwang Ki; Sohn, Yong Ho

2015-02-01

Inner retinal cleavage can be misdiagnosed as a glaucomatous retinal nerve fiber layer (RNFL) defect. This study was performed to characterize eyes with inner retinal cleavage. Inner retinal cleavage is defined as the appearance of a dark spindle-shaped space between the nerve fibers. Patients who presented at our institution with inner retinal cleavage were enrolled in the study. All participants were evaluated by fundus examination, visual field testing with standard automated perimetry, and optical coherence tomography (OCT) imaging. A total of 15 eyes of 11 subjects with inner retinal cleavage were included in the study. The median age of the subjects was 57 years (age range, 30-67 years). In each case, inner retinal cleavage was located adjacent to retinal blood vessels. Tissue bridging the cleavage area was observed in ten eyes. Six eyes had epiretinal membranes (ERMs), two eyes had glaucoma, and one eye had ERM in addition to glaucoma. Six eyes with inner retinal cleavage without combined ocular abnormalities had highly myopic refractive error (-6.50 to -8.50 diopters). Cross-sectional OCT images of the areas of inner retinal cleavage demonstrated defects with irregular margins and empty spaces in the inner layers of the retina. During the follow-up period, no eye showed changes in inner retinal layer cleavage or visual field sensitivity. Inner retinal cleavage was found in eyes with high myopia or ERMs. Inner retinal cleavage was associated with structural changes distinct from those associated with glaucomatous RNFL defects.

Cone dysfunctions in retinitis pigmentosa with retinal nerve fiber layer thickening.

PubMed

Sobacı, Güngör; Ozge, Gökhan; Gündoğan, Fatih Ç

2012-01-01

To investigate whether or not thicker retinal nerve fiber layer (RNFL) in retinitis pigmentosa (RP) patients relates to functional abnormalities of the photoreceptors. Optical coherence tomography-based RNFL thickness was measured by Stratus-3™ (Zeiss, Basel, Switzerland) optical coherence tomography and electroretinogram (ERG) recordings made using the RETI-port(®) system (Roland, Wiesbaden, Germany) in 27 patients with retinitis pigmentosa and in 30 healthy subjects. Photopic ERG b-wave amplitude, cone ERG b-wave latency, 30 Hz flicker amplitude, and 30 Hz flicker latency had significant correlations to the RNFL-temporal (r = -0.55, P = 0.004, r = 0.68, P = 0.001, r = -0.65, P = 0.001, and r = -0.52, P = 0.007, respectively). Eyes with thicker RNFL (ten eyes) differed significantly from those with thinner RNFL (eight eyes) regarding cone ERG b-wave latency values only (P = 0.001). Thicker RNFL in patients with retinitis pigmentosa may be associated with functional abnormality of the cone system.

Progressive outer retinal necrosis (PORN) in AIDS patients: a different appearance of varicella-zoster retinitis.

PubMed

Pavesio, C E; Mitchell, S M; Barton, K; Schwartz, S D; Towler, H M; Lightman, S

1995-01-01

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

Retinal Oxygen: from animals to humans

PubMed Central

Linsenmeier, Robert A.; Zhang, Hao F.

2017-01-01

This article discusses retinal oxygenation and retinal metabolism by focusing on measurements made with two of the principal methods used to study O2 in the retina: measurements of PO2 with oxygen-sensitive microelectrodes in vivo in animals with a retinal circulation similar to that of humans, and oximetry, which can be used non-invasively in both animals and humans to measure O2 concentration in retinal vessels. Microelectrodes uniquely have high spatial resolution, allowing the mapping of PO2 in detail, and when combined with mathematical models of diffusion and consumption, they provide information about retinal metabolism. Mathematical models, grounded in experiments, can also be used to simulate situations that are not amenable to experimental study. New methods of oximetry, particularly photoacoustic ophthalmoscopy and visible light optical coherence tomography, provide depth-resolved methods that can separate signals from blood vessels and surrounding tissues, and can be combined with blood flow measures to determine metabolic rate. We discuss the effects on retinal oxygenation of illumination, hypoxia and hyperoxia, and describe retinal oxygenation in diabetes, retinal detachment, arterial occlusion, and macular degeneration. We explain how the metabolic measurements obtained from microelectrodes and imaging are different, and how they need to be brought together in the future. Finally, we argue for revisiting the clinical use of hyperoxia in ophthalmology, particularly in retinal arterial occlusions and retinal detachment, based on animal research and diffusion theory. PMID:28109737

Cytomegalovirus Retinitis: A Review.

PubMed

Port, Alexander D; Orlin, Anton; Kiss, Szilard; Patel, Sarju; D'Amico, Donald J; Gupta, Mrinali P

2017-05-01

Cytomegalovirus (CMV) is a ubiquitous DNA herpes virus that causes significant morbidity and mortality in immunocompromised individuals. CMV retinitis is a potentially blinding manifestation of CMV infection that was commonly seen in advanced acquired immunodeficiency syndrome (AIDS) in the era before modern combination antiretroviral therapy era, but is also recognized in patients with immune deficiency from multiple causes. The advent of and advances in antiretroviral therapies for human immunodeficiency virus have decreased the incidence of CMV retinitis by over 90% among AIDS patients, and improved visual outcomes in those affected. The diagnosis is generally a clinical one, and treatment modalities include systemic and intravitreal antiviral medications. Retinal detachment and immune recovery uveitis are sight-threatening complications of CMV retinitis that require specific treatments.

Somatostatin protects human retinal pericytes from inflammation mediated by microglia.

PubMed

Mazzeo, Aurora; Arroba, Ana I; Beltramo, Elena; Valverde, Angela M; Porta, Massimo

2017-11-01

Diabetic retinopathy (DR) is usually considered a microvascular disease. However, involvement of the neuroretina in the early stages of DR has recently gained major credit. Inflammatory processes, leading to glial activation and neuronal apoptosis, develop early in the retina of diabetic subjects. Pericytes constitute a link between the vascular and the neural retina, play a central role in blood-retinal barrier maintenance, and may influence neuroinflammation. Somatostatin (SST) is a potent neuroprotective factor, which is down-regulated during early DR. In this paper, we have investigated the effects of the inflammatory signals triggered by the activation of microglia on inflammation and apoptosis/survival pathways in pericytes. Microglia cells (Bv-2) were stimulated with lipopolysaccharide (LPS) and/or SST. Human retinal pericytes (HRP) were exposed to conditioned media (CM) collected from Bv-2 cells in physiological conditions and in the settings described above. A panel of inflammation, apoptosis and survival mediators was analyzed. HRP treated with LPS-CM showed a significant increase of pro-inflammatory (iNos and TNFα) and pro-apoptotic mediators (FasL, active caspase-8, tBid and Bax), and a concomitant decrease in pro-survival factors (BclxL and pAkt). SST added to LPS was able to counteract these effects in all conditions. In conclusion, SST is able to modulate apoptosis/survival pathways in HRP during microglia-mediated inflammation. These results demonstrate a crosstalk between microglia and retinal pericytes, evidencing a possible defensive role of microglia in the early phases of DR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Uncoupling protein 2 deficiency mimics the effects of hypoxia and endoplasmic reticulum stress on mitochondria and triggers pseudohypoxic pulmonary vascular remodeling and pulmonary hypertension.

PubMed

Dromparis, Peter; Paulin, Roxane; Sutendra, Gopinath; Qi, Andrew C; Bonnet, Sébastien; Michelakis, Evangelos D

2013-07-05

Mitochondrial signaling regulates both the acute and the chronic response of the pulmonary circulation to hypoxia, and suppressed mitochondrial glucose oxidation contributes to the apoptosis-resistance and proliferative diathesis in the vascular remodeling in pulmonary hypertension. Hypoxia directly inhibits glucose oxidation, whereas endoplasmic reticulum (ER)-stress can indirectly inhibit glucose oxidation by decreasing mitochondrial calcium (Ca²⁺m levels). Both hypoxia and ER stress promote proliferative pulmonary vascular remodeling. Uncoupling protein 2 (UCP2) has been shown to conduct calcium from the ER to mitochondria and suppress mitochondrial function. We hypothesized that UCP2 deficiency reduces Ca²⁺m in pulmonary artery smooth muscle cells (PASMCs), mimicking the effects of hypoxia and ER stress on mitochondria in vitro and in vivo, promoting normoxic hypoxia inducible factor-1α activation and pulmonary hypertension. Ucp2 knockout (KO)-PASMCs had lower mitochondrial calcium than Ucp2 wildtype (WT)-PASMCs at baseline and during histamine-stimulated ER-Ca²⁺ release. Normoxic Ucp2KO-PASMCs had mitochondrial hyperpolarization, lower Ca²⁺-sensitive mitochondrial enzyme activity, reduced levels of mitochondrial reactive oxygen species and Krebs' cycle intermediates, and increased resistance to apoptosis, mimicking the hypoxia-induced changes in Ucp2WT-PASMC. Ucp2KO mice spontaneously developed pulmonary vascular remodeling and pulmonary hypertension and exhibited a pseudohypoxic state with pulmonary vascular and systemic hypoxia inducible factor-1α activation (increased hematocrit), not exacerbated further by chronic hypoxia. This first description of the role of UCP2 in oxygen sensing and in pulmonary hypertension vascular remodeling may open a new window in biomarker and therapeutic strategies.

Retinitis pigmentosa, Coats disease and uveitis.

PubMed

Solomon, A; Banin, E; Anteby, I; Benezra, D

1999-01-01

To study the anamnestic immune response to retinal specific antigens of two patients suffering from a rare triad of retinitis pigmentosa, Coats disease and uveitis. 17-year-old girl presented with an acute episode of panuveitis, and her 19-year-old brother suffered from chronic uveitis. On examination, both patients showed retinal vascular changes and subretinal exudations typical of Coats disease, with bone-spicule pigmentary changes as observed in retinitis pigmentosa. All routine examinations were unrevealing. However, the peripheral lymphocytes from these two siblings gave a specific anamnestic response to retinal antigens in vitro. A stimulation index of 4.6 was obtained when the sister's lymphocytes were stimulated with interphotoreceptor binding protein, IRBP--during the acute stage of the uveitis. The brother's lymphocytes showed a stimulation index of 2.7 towards S-Ag during the chronic phase of his uveitic condition. These results indicate that autoimmunity towards retinal antigens may play some role in specific types of retinitis pigmentosa. Whether these autoimmune reactions are a primary pathological mechanism or are secondary to the extensive destruction of the photoreceptor layer resulting from the retinitis pigmentosa remains debatable.

Lithium promotes DNA stability and survival of ischemic retinal neurocytes by upregulating DNA ligase IV.

PubMed

Yang, Ying; Wu, Nandan; Tian, Sijia; Li, Fan; Hu, Huan; Chen, Pei; Cai, Xiaoxiao; Xu, Lijun; Zhang, Jing; Chen, Zhao; Ge, Jian; Yu, Keming; Zhuang, Jing

2016-11-17

Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia-reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level. Furthermore, we also demonstrate that nuclear respiratory factor 1 (Nrf-1) and phosphorylated cyclic AMP-response element binding protein-1 (P-CREB1) bind to ligase IV promoter to cause upregulation of ligase IV in neurocytes. The ischemic upregulation of Nrf-1 and lithium-induced increase of P-CREB1 cooperate to promote transcription of ligase IV. Short hairpin RNAs against Nrf-1 and CREB1 could significantly inhibit the increase in promoter activity and expression of ligase IV observed in the control oligos following lithium treatment in retinal neurocytes. More importantly, ischemic stimulation triggers the expression of ligase IV. Taken together, our results thus reveal a novel mechanism that lithium offers neuroprotection from ischemia-induced damage by enhancing DNA NHEJ repair.

Lithium promotes DNA stability and survival of ischemic retinal neurocytes by upregulating DNA ligase IV

PubMed Central

Yang, Ying; Wu, Nandan; Tian, Sijia; Li, Fan; Hu, Huan; Chen, Pei; Cai, Xiaoxiao; Xu, Lijun; Zhang, Jing; Chen, Zhao; Ge, Jian; Yu, Keming; Zhuang, Jing

2016-01-01

Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia–reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level. Furthermore, we also demonstrate that nuclear respiratory factor 1 (Nrf-1) and phosphorylated cyclic AMP-response element binding protein-1 (P-CREB1) bind to ligase IV promoter to cause upregulation of ligase IV in neurocytes. The ischemic upregulation of Nrf-1 and lithium-induced increase of P-CREB1 cooperate to promote transcription of ligase IV. Short hairpin RNAs against Nrf-1 and CREB1 could significantly inhibit the increase in promoter activity and expression of ligase IV observed in the control oligos following lithium treatment in retinal neurocytes. More importantly, ischemic stimulation triggers the expression of ligase IV. Taken together, our results thus reveal a novel mechanism that lithium offers neuroprotection from ischemia-induced damage by enhancing DNA NHEJ repair. PMID:27853172

Retinal oxygen extraction in humans

NASA Astrophysics Data System (ADS)

Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

2015-10-01

Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.

Retinal oxygen extraction in humans

PubMed Central

Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

2015-01-01

Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy. PMID:26503332

Retinal abnormalities in β-thalassemia major

PubMed Central

Bhoiwala, Devang L.; Dunaief, Joshua L.

2015-01-01

Patients with beta (β)-thalassemia (β-TM: thalassemia major, β-TI: thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelium degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-TM are transfusion dependent and require iron chelation therapy (ICT) in order to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by ICT. Some who were never treated with ICT exhibited retinopathy, and others receiving ICT had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-TM viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. PMID:26325202

Evaluation of patient suitability for a retinal prosthesis using structural and functional tests of inner retinal integrity

NASA Astrophysics Data System (ADS)

Huang, Qiuhen; Chowdhury, Vivek; Coroneo, Minas Theodore

2009-06-01

The purpose of this study was to assess inner retinal structure and function in patients with retinitis pigmentosa (RP) using optical coherence tomography (OCT) imaging of the retina, and electrical stimulation of the retina with a contact lens electrode. OCT images of 17 RP patients were acquired at the macula and at four quadrants of the peripheral retina in both eyes. Analysis was made of the residual inner retinal thickness and nerve fibre layer thickness in RP patients, and this was compared to normal controls. Eight of these patients further underwent contact lens electrical stimulation of one eye and thresholds for phosphene perception were obtained. OCT imaging showed a significant amount of inner retinal preservation in the peripheral retina and the macula of RP patients despite severe visual acuity and visual field loss. Phosphene thresholds were obtained across the range of pulse durations tested but were much higher than those obtained in normal controls. Phosphene thresholds in RP patients moderately correlated with inner retinal thicknesses as measured by OCT. Preservation of inner retinal structure in patients with RP and the responsiveness of these eyes to electrical stimulation suggest adequate inner retinal preservation for a retinal prosthesis to be successful.

Cytomegalovirus retinitis associated with acquired immunodeficiency syndrome.

PubMed

Geng, Shuang; Ye, Jun-jie; Zhao, Jia-liang; Li, Tai-sheng; Han, Yang

2011-04-01

Cytomegalovirus (CMV) retinitis is the most severe intraocular complication that results in total retinal destruction and loss of visual acuity in patients with acquired immunodeficiency syndrome (AIDS). This study aimed to investigate the fundus characteristics, systemic manifestations and therapeutic outcomes of CMV retinitis associated with AIDS. It was a retrospective case series. CMV retinitis was present in 39 eyes (25 patients). Best corrected visual acuities, anterior segment, fundus features, fundus fluorescence angiography (FFA) and CD4(+) T-lymphocyte counts of the patients with CMV retinitis associated with AIDS were analyzed. Intravitreal injections of ganciclovir (400 µg) were performed in 4 eyes (2 patients). Retinal vasculitis, dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface were present in 28 eyes. The vitreous was clear or mildly opaque. Late stage of the retinopathy was demonstrated in 8 eyes characterized as atrophic retina, sclerotic and attenuated vessels, retinal pigment epithelium (RPE) atrophy, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The average CD4(+) T-lymphocyte count in peripheral blood of the patients with CMV retinitis was (30.6 ± 25.3) × 10(6)/L (range, (0 - 85) × 10(6)/L). After intravitreal injections of ganciclovir, visual acuity was improved and fundus lesions regressed. CMV retinitis is the most severe and the most common intraocular complication in patients with AIDS. For the patients with yellow-white retinal lesions, hemorrhage and retinal vasculitis without clear cause, human immunodeficiency virus (HIV) serology should be performed. Routine eye examination is also indicated in HIV positive patients.

Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid.

PubMed

Sanie-Jahromi, Fatemeh; Ahmadieh, Hamid; Soheili, Zahra-Soheila; Davari, Maliheh; Ghaderi, Shima; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Deezagi, Abdolkhalegh; Pakravesh, Jalil; Bagheri, Abouzar

2012-04-10

Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers) during treatment of human retinal pigment epithelium (RPE) cells with amniotic fluid (AF), RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1) confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays.

PubMed

Light, Jacob G; Fransen, James W; Adekunle, Adewumi N; Adkins, Alice; Pangeni, Gobinda; Loudin, James; Mathieson, Keith; Palanker, Daniel V; McCall, Maureen A; Pardue, Machelle T

2014-11-01

Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission. Published

Cone dysfunctions in retinitis pigmentosa with retinal nerve fiber layer thickening

PubMed Central

Sobacı, Güngör; Özge, Gökhan; Gündoğan, Fatih Ç

2012-01-01

Purpose To investigate whether or not thicker retinal nerve fiber layer (RNFL) in retinitis pigmentosa (RP) patients relates to functional abnormalities of the photoreceptors. Methods Optical coherence tomography-based RNFL thickness was measured by Stratus-3™ (Zeiss, Basel, Switzerland) optical coherence tomography and electroretinogram (ERG) recordings made using the RETI-port® system (Roland, Wiesbaden, Germany) in 27 patients with retinitis pigmentosa and in 30 healthy subjects. Results Photopic ERG b-wave amplitude, cone ERG b-wave latency, 30 Hz flicker amplitude, and 30 Hz flicker latency had significant correlations to the RNFL-temporal (r = −0.55, P = 0.004, r = 0.68, P = 0.001, r = −0.65, P = 0.001, and r = −0.52, P = 0.007, respectively). Eyes with thicker RNFL (ten eyes) differed significantly from those with thinner RNFL (eight eyes) regarding cone ERG b-wave latency values only (P = 0.001). Conclusion Thicker RNFL in patients with retinitis pigmentosa may be associated with functional abnormality of the cone system. PMID:22536039

Oleoyl serine, an endogenous N-acyl amide, modulates bone remodeling and mass.

PubMed

Smoum, Reem; Bar, Arik; Tan, Bo; Milman, Garry; Attar-Namdar, Malka; Ofek, Orr; Stuart, Jordyn M; Bajayo, Alon; Tam, Joseph; Kram, Vardit; O'Dell, David; Walker, Michael J; Bradshaw, Heather B; Bab, Itai; Mechoulam, Raphael

2010-10-12

Bone mass is determined by a continuous remodeling process, whereby the mineralized matrix is being removed by osteoclasts and subsequently replaced with newly formed bone tissue produced by osteoblasts. Here we report the presence of endogenous amides of long-chain fatty acids with amino acids or with ethanolamine (N-acyl amides) in mouse bone. Of these compounds, N-oleoyl-l-serine (OS) had the highest activity in an osteoblast proliferation assay. In these cells, OS triggers a Gi-protein-coupled receptor and Erk1/2. It also mitigates osteoclast number by promoting osteoclast apoptosis through the inhibition of Erk1/2 phosphorylation and receptor activator of nuclear-κB ligand (RANKL) expression in bone marrow stromal cells and osteoblasts. In intact mice, OS moderately increases bone volume density mainly by inhibiting bone resorption. However, in a mouse ovariectomy (OVX) model for osteoporosis, OS effectively rescues bone loss by increasing bone formation and markedly restraining bone resorption. The differential effect of exogenous OS in the OVX vs. intact animals is apparently a result of an OVX-induced decrease in skeletal OS levels. These data show that OS is a previously unexplored lipid regulator of bone remodeling. It represents a lead to antiosteoporotic drug discovery, advantageous to currently available therapies, which are essentially either proformative or antiresorptive.

Peripheral retinal non-perfusion and treatment response in branch retinal vein occlusion.

PubMed

Abri Aghdam, Kaveh; Reznicek, Lukas; Soltan Sanjari, Mostafa; Framme, Carsten; Bajor, Anna; Klingenstein, Annemarie; Kernt, Marcus; Seidensticker, Florian

2016-01-01

To evaluate the association between the size of peripheral retinal non-perfusion and the number of intravitreal ranibizumab injections in patients with treatment-naive branch retinal vein occlusion (BRVO) and macular edema. A total of 53 patients with treatment-naive BRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography (OCT) imaging and ultra wide-field fluorescein angiography (UWFA). Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmological Society. Two independent, masked graders quantified the areas of peripheral retinal non-perfusion. Intravitreal injections improved best-corrected visual acuity (BCVA) significantly from 22.23±16.33 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters to 36.23±15.19 letters (P<0.001), and mean central subfield thickness significantly reduced from 387±115 µm to 321±115 µm (P=0.01). Mean number of intravitreal ranibizumab injections was 3.61±1.56. The size of retinal non-perfusion correlated significantly with the number of intravitreal ranibizumab injections (R=0.724, P<0.001). Peripheral retinal non-perfusion in patients with BRVO associates significantly with intravitreal ranibizumab injections in patients with BRVO and macular edema.

Peripheral retinal non-perfusion and treatment response in branch retinal vein occlusion

PubMed Central

Abri Aghdam, Kaveh; Reznicek, Lukas; Soltan Sanjari, Mostafa; Framme, Carsten; Bajor, Anna; Klingenstein, Annemarie; Kernt, Marcus; Seidensticker, Florian

2016-01-01

AIM To evaluate the association between the size of peripheral retinal non-perfusion and the number of intravitreal ranibizumab injections in patients with treatment-naive branch retinal vein occlusion (BRVO) and macular edema. METHODS A total of 53 patients with treatment-naive BRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography (OCT) imaging and ultra wide-field fluorescein angiography (UWFA). Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmological Society. Two independent, masked graders quantified the areas of peripheral retinal non-perfusion. RESULTS Intravitreal injections improved best-corrected visual acuity (BCVA) significantly from 22.23±16.33 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters to 36.23±15.19 letters (P<0.001), and mean central subfield thickness significantly reduced from 387±115 µm to 321±115 µm (P=0.01). Mean number of intravitreal ranibizumab injections was 3.61±1.56. The size of retinal non-perfusion correlated significantly with the number of intravitreal ranibizumab injections (R=0.724, P<0.001). CONCLUSION Peripheral retinal non-perfusion in patients with BRVO associates significantly with intravitreal ranibizumab injections in patients with BRVO and macular edema. PMID:27366688

Retinal vasculature classification using novel multifractal features

NASA Astrophysics Data System (ADS)

Ding, Y.; Ward, W. O. C.; Duan, Jinming; Auer, D. P.; Gowland, Penny; Bai, L.

2015-11-01

Retinal blood vessels have been implicated in a large number of diseases including diabetic retinopathy and cardiovascular diseases, which cause damages to retinal blood vessels. The availability of retinal vessel imaging provides an excellent opportunity for monitoring and diagnosis of retinal diseases, and automatic analysis of retinal vessels will help with the processes. However, state of the art vascular analysis methods such as counting the number of branches or measuring the curvature and diameter of individual vessels are unsuitable for the microvasculature. There has been published research using fractal analysis to calculate fractal dimensions of retinal blood vessels, but so far there has been no systematic research extracting discriminant features from retinal vessels for classifications. This paper introduces new methods for feature extraction from multifractal spectra of retinal vessels for classification. Two publicly available retinal vascular image databases are used for the experiments, and the proposed methods have produced accuracies of 85.5% and 77% for classification of healthy and diabetic retinal vasculatures. Experiments show that classification with multiple fractal features produces better rates compared with methods using a single fractal dimension value. In addition to this, experiments also show that classification accuracy can be affected by the accuracy of vessel segmentation algorithms.

NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and Pulmonary Arterial Hypertension.

PubMed

Dumas, Sébastien J; Bru-Mercier, Gilles; Courboulin, Audrey; Quatredeniers, Marceau; Rücker-Martin, Catherine; Antigny, Fabrice; Nakhleh, Morad K; Ranchoux, Benoit; Gouadon, Elodie; Vinhas, Maria-Candida; Vocelle, Matthieu; Raymond, Nicolas; Dorfmüller, Peter; Fadel, Elie; Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

2018-05-29

pulmonary arterial smooth muscle cells involved NMDAR activation and phosphorylated GluN1 subunit localization to cell-cell contacts, consistent with glutamatergic communication between proliferating human pulmonary arterial smooth muscle cells via NMDARs. Smooth-muscle NMDAR deficiency in mice attenuated the vascular remodeling triggered by chronic hypoxia, highlighting the role of vascular NMDARs in pulmonary hypertension. Pharmacological NMDAR blockade in the monocrotaline rat model of pulmonary hypertension had beneficial effects on cardiac and vascular remodeling, decreasing endothelial dysfunction, cell proliferation, and apoptosis resistance while disrupting the glutamate-NMDAR pathway in pulmonary arteries. These results reveal a dysregulation of the glutamate-NMDAR axis in the pulmonary arteries of patients with PAH and identify vascular NMDARs as targets for antiremodeling treatments in PAH. © 2018 American Heart Association, Inc.

Microsystems Technology for Retinal Implants

NASA Astrophysics Data System (ADS)

Weiland, James

2005-03-01

The retinal prosthesis is targeted to treat age-related macular degeneration, retinitis pigmentosa, and other outer retinal degenerations. Simulations of artificial vision have predicted that 600-1000 individual pixels will be needed if a retinal prosthesis is to restore function such as reading large print and face recognition. An implantable device with this many electrode contacts will require microsystems technology as part of its design. An implantable retinal prosthesis will consist of several subsystems including an electrode array and hermetic packaging. Microsystems and microtechnology approaches are being investigated as possible solutions for these design problems. Flexible polydimethylsiloxane (PDMS) substrate electrode arrays and silicon micromachined electrode arrays are under development. Inactive PDMS electrodes have been implanted in 3 dogs to assess mechanical biocompatibility. 3 dogs were followed for 6 months. The implanted was securely fastened to the retina with a single retinal tack. No post-operative complications were evident. The array remained within 100 microns of the retinal surface. Histological evaluation showed a well preserved retina underneath the electrode array. A silicon device with electrodes suspended on micromachined springs has been implanted in 4 dogs (2 acute implants, 2 chronic implants). The device, though large, could be inserted into the eye and positioned on the retina. Histological analysis of the retina from the spring electrode implants showed that spring mounted posts penetrated the retina, thus the device will be redesigned to reduce the strength of the springs. These initial implants will provide information for the designers to make the next generation silicon device. We conclude that microsystems technology has the potential to make possible a retinal prosthesis with 1000 individual contacts in close proximity to the retina.

Giant Retinal Tear With Retinal Detachment in Regressed Aggressive Posterior Retinopathy of Prematurity Treated by Laser.

PubMed

Chandra, Parijat; Tewari, Ruchir; Salunkhe, Nitesh; Kumawat, Devesh; Kumar, Vinod

2017-06-29

Rhegmatogenous retinal detachment after successfully regressed retinopathy of prematurity is a rare occurrence. Late onset rhegmatogenous retinal detachment has been reported infrequently. The authors report a case of aggressive posterior retinopathy of prematurity that underwent uneventful regression after laser photocoagulation and later developed an inoperable closed funnel retinal detachment due to a giant retinal tear. This case represents the earliest development of such complications in regressed aggressive posterior retinopathy of prematurity treated by laser. Development of a giant retinal tear has also not been previously reported after laser treatment. This case highlights that successful regression of severe retinopathy of prematurity does not safeguard against future complications and requires frequent long-term follow-up. [J Pediatr Ophthalmol Strabismus. 2017;54:e34-e36.]. Copyright 2017, SLACK Incorporated.

Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid

PubMed Central

2012-01-01

Background Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers) during treatment of human retinal pigment epithelium (RPE) cells with amniotic fluid (AF), RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Results Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1) confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Conclusion Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells. PMID:22490806

Automatic segmentation of pigment deposits in retinal fundus images of Retinitis Pigmentosa.

PubMed

Brancati, Nadia; Frucci, Maria; Gragnaniello, Diego; Riccio, Daniel; Di Iorio, Valentina; Di Perna, Luigi

2018-06-01

Retinitis Pigmentosa is an eye disease that presents with a slow loss of vision and then evolves until blindness results. The automatic detection of the early signs of retinitis pigmentosa acts as a great support to ophthalmologists in the diagnosis and monitoring of the disease in order to slow down the degenerative process. A large body of literature is devoted to the analysis of Retinitis Pigmentosa. However, all the existing approaches work on Optical Coherence Tomography (OCT) data, while hardly any attempts have been made working on fundus images. Fundus image analysis is a suitable tool in daily practice for an early detection of retinal diseases and the monitoring of their progression. Moreover, the fundus camera represents a low-cost and easy-access diagnostic system, which can be employed in resource-limited regions and countries. The fundus images of a patient suffering from retinitis pigmentosa are characterized by an attenuation of the vessels, a waxy disc pallor and the presence of pigment deposits. Considering that several methods have been proposed for the analysis of retinal vessels and the optic disk, this work focuses on the automatic segmentation of the pigment deposits in the fundus images. The image distortions are attenuated by applying a local pre-processing. Next, a watershed transformation is carried out to produce homogeneous regions. Working on regions rather than on pixels makes the method very robust to the high variability of pigment deposits in terms of color and shape, so allowing the detection even of small pigment deposits. The regions undergo a feature extraction procedure, so that a region classification process is performed by means of an outlier detection analysis and a rule set. The experiments have been performed on a dataset of images of patients suffering from retinitis pigmentosa. Although the images present a high variability in terms of color and illumination, the method provides a good performance in terms of

Bioelectronic retinal prosthesis

NASA Astrophysics Data System (ADS)

Weiland, James D.

2016-05-01

Retinal prosthesis have been translated to clinical use over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa and one device is in clinical trials for treatment of age-related macular degeneration. These devices provide partial sight restoration and patients use this improved vision in their everyday lives to navigate and to detect large objects. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. In particular, current retinal prostheses do not provide peripheral visions due to technical and surgical limitations, thus limiting the effectiveness of the treatment. This paper reviews recent results from human implant patients and presents technical approaches for peripheral vision.

Role of Bax in death of uninfected retinal cells during murine cytomegalovirus retinitis.

PubMed

Mo, Juan; Marshall, Brendan; Covar, Jason; Zhang, Nancy Y; Smith, Sylvia B; Atherton, Sally S; Zhang, Ming

2014-10-08

Extensive death of uninfected bystander neuronal cells is an important component of the pathogenesis of cytomegalovirus retinitis. Our previous results have shown that caspase 3-dependent and -independent pathways are involved in death of uninfected bystander cells during murine cytomegalovirus (MCMV) retinitis and also that Bcl-2, an important inhibitor of apoptosis via the Bax-mediated mitochondrial pathway, is downregulated during this process. The purpose of this study was to determine whether Bax-mediated mitochondrial damage has a significant role in the death of uninfected retinal cells. BALB/c mice, Bax(-/-) mice, or Bax(+/+) mice were immunosuppressed with methylprednisolone and infected with 5 × 10(3) plaque-forming units (PFU) of the K181 strain of MCMV via the supraciliary route. Injected eyes were analyzed by plaque assay, electron microscopy, hematoxylin and eosin (H&E) staining, TUNEL assay, Western blot (for caspase 3, caspase 12, Bax, receptor interacting protein-1 [RIP1] and receptor interacting protein-3 [RIP3]), as well as immunohistochemical staining for MCMV early antigen and cleaved caspase 3. Significantly more Bax was detected in mitochondrial fractions of MCMV-infected eyes than in mitochondrial fractions of mock-infected control eyes. Furthermore, the level of cleaved caspase 3 was significantly lower in MCMV-infected Bax(-/-) eyes than in MCMV-infected Bax(+/+) eyes. However, more caspase 3-independent cell death of uninfected bystander retinal cells and more cleaved RIP1 were observed in Bax(-/-) than in Bax(+/+) eyes. During MCMV retinitis, Bax is activated and has an important role in death of uninfected bystander retinal cells by caspase 3-dependent apoptosis. Although the exact mechanism remains to be deciphered, active Bax might also prevent death of some types of uninfected retinal cells by a caspase 3-independent pathway. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Role of Bax in Death of Uninfected Retinal Cells During Murine Cytomegalovirus Retinitis

PubMed Central

Mo, Juan; Marshall, Brendan; Covar, Jason; Zhang, Nancy Y.; Smith, Sylvia B.; Atherton, Sally S.; Zhang, Ming

2014-01-01

Purpose. Extensive death of uninfected bystander neuronal cells is an important component of the pathogenesis of cytomegalovirus retinitis. Our previous results have shown that caspase 3–dependent and –independent pathways are involved in death of uninfected bystander cells during murine cytomegalovirus (MCMV) retinitis and also that Bcl-2, an important inhibitor of apoptosis via the Bax-mediated mitochondrial pathway, is downregulated during this process. The purpose of this study was to determine whether Bax-mediated mitochondrial damage has a significant role in the death of uninfected retinal cells. Methods. BALB/c mice, Bax−/− mice, or Bax+/+ mice were immunosuppressed with methylprednisolone and infected with 5 × 103 plaque-forming units (PFU) of the K181 strain of MCMV via the supraciliary route. Injected eyes were analyzed by plaque assay, electron microscopy, hematoxylin and eosin (H&E) staining, TUNEL assay, Western blot (for caspase 3, caspase 12, Bax, receptor interacting protein-1 [RIP1] and receptor interacting protein-3 [RIP3]), as well as immunohistochemical staining for MCMV early antigen and cleaved caspase 3. Results. Significantly more Bax was detected in mitochondrial fractions of MCMV-infected eyes than in mitochondrial fractions of mock-infected control eyes. Furthermore, the level of cleaved caspase 3 was significantly lower in MCMV-infected Bax−/− eyes than in MCMV-infected Bax+/+ eyes. However, more caspase 3–independent cell death of uninfected bystander retinal cells and more cleaved RIP1 were observed in Bax−/− than in Bax+/+ eyes. Conclusions. During MCMV retinitis, Bax is activated and has an important role in death of uninfected bystander retinal cells by caspase 3–dependent apoptosis. Although the exact mechanism remains to be deciphered, active Bax might also prevent death of some types of uninfected retinal cells by a caspase 3–independent pathway. PMID:25298417

Tractional retinal detachment in Usher syndrome type II.

PubMed

Rani, Alka; Pal, Nikhil; Azad, Raj Vardhan; Sharma, Yog Raj; Chandra, Parijat; Vikram Singh, Deependra

2005-08-01

Retinal detachment is a rare complication in patients with retinitis pigmentosa. A case is reported of tractional retinal detachment in a patient with retinitis pigmentosa and sensorineural hearing loss, which was diagnosed as Usher syndrome type II. Because of the poor visual prognosis, the patient refused surgery in that eye. Tractional retinal detachment should be added to the differential diagnoses of visual loss in patients with retinitis pigmentosa.

Inherited Retinal Degenerative Disease Registry

ClinicalTrials.gov

2017-09-13

Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

Ruptured retinal arterial macroaneurysm: diagnosis and management.

PubMed

Speilburg, Ashley M; Klemencic, Stephanie A

2014-01-01

Retinal arterial macroaneurysm is an acquired, focal dilation of a retinal artery, typically occurring within the first three bifurcations of the central retinal artery. The clinical presentation of a retinal arterial macroaneurysm is highly variable, making initial diagnosis difficult and differentials many. Identification of retinal arterial macroaneurysms is crucial to appropriately co-manage with the primary care physician for hypertension control. Prognosis is generally good and observation is often an adequate treatment. However, in cases of macular threat or involvement, some treatment options are available and referral to a retinal specialist is indicated. Copyright © 2013 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment.

PubMed

Santos, Fátima Milhano; Gaspar, Leonor Mesquita; Ciordia, Sergio; Rocha, Ana Sílvia; Castro E Sousa, João Paulo; Paradela, Alberto; Passarinha, Luís António; Tomaz, Cândida Teixeira

2018-04-11

Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition characterized by a physical separation between neurosensory retina and retinal pigment epithelium. Quantitative proteomics can help to understand the changes that occur at the cellular level during RRD, providing additional information about the molecular mechanisms underlying its pathogenesis. In the present study, iTRAQ labeling was combined with two-dimensional LC-ESI-MS/MS to find expression changes in the proteome of vitreous from patients with RRD when compared to control samples. A total of 150 proteins were found differentially expressed in the vitreous of patients with RRD, including 96 overexpressed and 54 underexpressed. Several overexpressed proteins, several such as glycolytic enzymes (fructose-bisphosphate aldolase A, gamma-enolase, and phosphoglycerate kinase 1), glucose transporters (GLUT-1), growth factors (metalloproteinase inhibitor 1), and serine protease inhibitors (plasminogen activator inhibitor 1) are regulated by HIF-1, which suggests that HIF-1 signaling pathway can be triggered in response to RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Nevertheless, the differentially expressed proteins found in this study suggest that different mechanisms are activated after RRD to promote the survival of retinal cells through complex cellular responses.

iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment

PubMed Central

Gaspar, Leonor Mesquita; Ciordia, Sergio; Rocha, Ana Sílvia; Castro e Sousa, João Paulo; Paradela, Alberto

2018-01-01

Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition characterized by a physical separation between neurosensory retina and retinal pigment epithelium. Quantitative proteomics can help to understand the changes that occur at the cellular level during RRD, providing additional information about the molecular mechanisms underlying its pathogenesis. In the present study, iTRAQ labeling was combined with two-dimensional LC-ESI-MS/MS to find expression changes in the proteome of vitreous from patients with RRD when compared to control samples. A total of 150 proteins were found differentially expressed in the vitreous of patients with RRD, including 96 overexpressed and 54 underexpressed. Several overexpressed proteins, several such as glycolytic enzymes (fructose-bisphosphate aldolase A, gamma-enolase, and phosphoglycerate kinase 1), glucose transporters (GLUT-1), growth factors (metalloproteinase inhibitor 1), and serine protease inhibitors (plasminogen activator inhibitor 1) are regulated by HIF-1, which suggests that HIF-1 signaling pathway can be triggered in response to RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Nevertheless, the differentially expressed proteins found in this study suggest that different mechanisms are activated after RRD to promote the survival of retinal cells through complex cellular responses. PMID:29641463

Viral infection of the marine alga Emiliania huxleyi triggers lipidome remodeling and induces the production of highly saturated triacylglycerol.

PubMed

Malitsky, Sergey; Ziv, Carmit; Rosenwasser, Shilo; Zheng, Shuning; Schatz, Daniella; Porat, Ziv; Ben-Dor, Shifra; Aharoni, Asaph; Vardi, Assaf

2016-04-01

Viruses that infect marine photosynthetic microorganisms are major ecological and evolutionary drivers of microbial food webs, estimated to turn over more than a quarter of the total photosynthetically fixed carbon. Viral infection of the bloom-forming microalga Emiliania huxleyi induces the rapid remodeling of host primary metabolism, targeted towards fatty acid metabolism. We applied a liquid chromatography-mass spectrometry (LC-MS)-based lipidomics approach combined with imaging flow cytometry and gene expression profiling to explore the impact of viral-induced metabolic reprogramming on lipid composition. Lytic viral infection led to remodeling of the cellular lipidome, by predominantly inducing the biosynthesis of highly saturated triacylglycerols (TAGs), coupled with a significant accumulation of neutral lipids within lipid droplets. Furthermore, TAGs were found to be a major component (77%) of the lipidome of isolated virions. Interestingly, viral-induced TAGs were significantly more saturated than TAGs produced under nitrogen starvation. This study highlights TAGs as major products of the viral-induced metabolic reprogramming during the host-virus interaction and indicates a selective mode of membrane recruitment during viral assembly, possibly by budding of the virus from specialized subcellular compartments. These findings provide novel insights into the role of viruses infecting microalgae in regulating metabolism and energy transfer in the marine environment and suggest their possible biotechnological application in biofuel production. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Retinal abnormalities in β-thalassemia major.

PubMed

Bhoiwala, Devang L; Dunaief, Joshua L

2016-01-01

Patients with beta (β)-thalassemia (β-TM: β-thalassemia major, β-TI: β-thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelial degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-thalassemia major are transfusion dependent and require iron chelation therapy to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by iron chelation therapy. Some who were never treated with iron chelation therapy exhibited retinopathy, and others receiving iron chelation therapy had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-thalassemia major viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreased Retinal-Choroidal Blood Flow in Retinitis Pigmentosa as measured by MRI

PubMed Central

Zhang, Yi; Harrison, Joseph M; Nateras, Oscar San Emeterio; Chalfin, Steven; Duong, Timothy Q

2013-01-01

Purpose To evaluate retinal and choroidal blood flow (BF) using high-resolution magnetic resonance imaging (MRI) as well as visual function measured by the electroretinogram (ERG) in patients with retinitis pigmentosa (RP). Methods MRI studies were performed in 6 RP patients (29-67 years) and 5 healthy volunteers (29-64 years) on a 3-Tesla scanner with a custom-made surface coil. Quantitative BF was measured using the pseudo-continuous arterial-spin-labeling technique at 0.5x0.8x6.0mm. Full-field ERGs of all patients were recorded. Amplitudes and implicit times of standard ERGs were analyzed. Results Basal BF in the posterior retinal-choroid was 142±16 ml/100ml/min (or 1.14±0.13 μl/mm2/min) in the control group and was 70±19 ml/100ml/min (or 0.56±0.15 μl/mm2/min) in the RP group. Retinal-choroidal BF was significantly reduced by 52±8% in RP patients compared to controls (P<0.05). ERG a- and b-wave amplitudes of RP patients were reduced and b-wave implicit times were delayed. There were statistically significant correlations between a-wave amplitude and BF value (r=0.9, P<0.05) but not between b-wave amplitude and BF value (r =0.7, P=0.2). Conclusions This study demonstrates a novel non-invasive MRI approach to measure quantitative retinal and choroidal BF in RP patients. We found that retinal-choroidal BF was markedly reduced and significantly correlated with reduced amplitudes of the a-wave of the standard combined ERG. PMID:23408312

Retinal Arterioles in Hypo-, Normo-, and Hypertensive Subjects Measured Using Adaptive Optics.

PubMed

Hillard, Jacob G; Gast, Thomas J; Chui, Toco Y P; Sapir, Dan; Burns, Stephen A

2016-08-01

Small artery and arteriolar walls thicken due to elevated blood pressure. Vascular wall thickness show a correlation with hypertensive subject history and risk for stroke and cardiovascular events. The inner and outer diameter of retinal arterioles from less than 10 to over 150 μm were measured using a multiply scattered light adaptive optics scanning laser ophthalmoscope (AOSLO). These measurements were made on three populations, one with habitual blood pressures less than 100/70 mm Hg, one with normal blood pressures without medication, and one with managed essential hypertension. The wall to lumen ratio was largest for the smallest arterioles for all three populations. Data from the hypotensive group had a linear relationship between outer and inner diameters ( r 2 = 0.99) suggesting a similar wall structure in individuals prior to elevated blood pressures. Hypertensive subjects fell below the 95% confidence limits for the hypotensive relationship and had larger wall to lumen ratios and the normotensive group results fell between the other two groups. High-resolution retinal imaging of subjects with essential hypertension showed a significant decrease in vessel inner diameter for a given outer diameter, and increases in wall to lumen ratio and wall cross-sectional areas over the entire range of vessel diameters and suggests that correcting for vessel size may improve the ability to identify significant vascular changes. High-resolution imaging allows precise measurement of vasculature and by comparing results across risk populations may allow improved identification of individuals undergoing hypertensive arterial wall remodeling.

[Retinal vasculitis and systemic diseases].

PubMed

Gascon, P; Jarrot, P-A; Matonti, F; Kaplanski, G

2018-06-19

Retinal vasculitis (RV) is an inflammation of retinal blood vessels that can be associated with uveitis or be isolated, and can induce vascular occlusion and retinal ischemia. Visual acuity can be severely affected in case of macular involvement or neovessel formation. The diagnosis relies on fundoscopy and fluorescein angiography. Systemic diseases may be associated with RV, the most frequently encountered are Behçet's disease, sarcoidosis or multiple sclerosis, all predominantly associated with venous involvement, whereas systemic lupus erythematosus and necrotizing vasculitis are less frequently observed and predominantly associated with arterial or mixed vasculitis. Treatments are usually aggressive in order to preserve a good visual acuity and to reduce retinal inflammation and chronic ischemia. Steroids, immunosuppressive drugs, retinal laser photocoagulation, intravitreal anti-VEGF injections are usual treatments and more recently, anti-TNFalpha monoclonal therapeutic antibodies have been shown to be very successful. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

Expression Profiling Analysis Reveals Key MicroRNA-mRNA Interactions in Early Retinal Degeneration in Retinitis Pigmentosa.

PubMed

Anasagasti, Ander; Ezquerra-Inchausti, Maitane; Barandika, Olatz; Muñoz-Culla, Maider; Caffarel, María M; Otaegui, David; López de Munain, Adolfo; Ruiz-Ederra, Javier

2018-05-01

The aim of this study was to identify differentially expressed microRNAs (miRNAs) that might play an important role in the etiology of retinal degeneration in a genetic mouse model of retinitis pigmentosa (rd10 mice) at initial stages of the disease. miRNAs-mRNA interaction networks were generated for analysis of biological pathways involved in retinal degeneration. Of more than 1900 miRNAs analyzed, we selected 19 miRNAs on the basis of (1) a significant differential expression in rd10 retinas compared with control samples and (2) an inverse expression relationship with predicted mRNA targets involved in biological pathways relevant to retinal biology and/or degeneration. Seven of the selected miRNAs have been associated with retinal dystrophies, whereas, to our knowledge, nine have not been previously linked to any disease. This study contributes to our understanding of the etiology and progression of retinal degeneration.

Concentric retinitis pigmentosa: clinicopathologic correlations.

PubMed

Milam, A H; De Castro, E B; Smith, J E; Tang, W X; John, S K; Gorin, M B; Stone, E M; Aguirre, G D; Jacobson, S G

2001-10-01

Progressive concentric (centripetal) loss of vision is one pattern of visual field loss in retinitis pigmentosa. This study provides the first clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell specific antibodies. Unrelated simplex/multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric field loss, normal or near normal rod and cone sensitivity within the preserved visual field, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective

Determination of retinal surface area.

PubMed

Nagra, Manbir; Gilmartin, Bernard; Thai, Ngoc Jade; Logan, Nicola S

2017-09-01

Previous attempts at determining retinal surface area and surface area of the whole eye have been based upon mathematical calculations derived from retinal photographs, schematic eyes and retinal biopsies of donor eyes. 3-dimensional (3-D) ocular magnetic resonance imaging (MRI) allows a more direct measurement, it can be used to image the eye in vivo, and there is no risk of tissue shrinkage. The primary purpose of this study is to compare, using T2-weighted 3D MRI, retinal surface areas for superior-temporal (ST), inferior-temporal (IT), superior-nasal (SN) and inferior-nasal (IN) retinal quadrants. An ancillary aim is to examine whether inter-quadrant variations in area are concordant with reported inter-quadrant patterns of susceptibility to retinal breaks associated with posterior vitreous detachment (PVD). Seventy-three adult participants presenting without retinal pathology (mean age 26.25 ± 6.06 years) were scanned using a Siemens 3-Tesla MRI scanner to provide T2-weighted MR images that demarcate fluid-filled internal structures for the whole eye and provide high-contrast delineation of the vitreous-retina interface. Integrated MRI software generated total internal ocular surface area (TSA). The second nodal point was used to demarcate the origin of the peripheral retina in order to calculate total retinal surface area (RSA) and quadrant retinal surface areas (QRSA) for ST, IT, SN, and IN quadrants. Mean spherical error (MSE) was -2.50 ± 4.03D and mean axial length (AL) 24.51 ± 1.57 mm. Mean TSA and RSA for the RE were 2058 ± 189 and 1363 ± 160 mm 2 , respectively. Repeated measures anova for QRSA data indicated a significant difference within-quadrants (P < 0.01) which, contrasted with ST (365 ± 43 mm 2 ), was significant for IT (340 ± 40 mm 2 P < 0.01), SN (337 ± 40 mm 2 P < 0.01) and IN (321 ± 39 mm 2 P < 0.01) quadrants. For all quadrants, QRSA was significantly correlated with AL (P < 0.01) and exhibited

Evaluation of the Zeiss retinal vessel analyser

PubMed Central

Polak, K.; Dorner, G.; Kiss, B.; Polska, E.; Findl, O.; Rainer, G.; Eichler, H.; Schmetterer, L.

2000-01-01

AIM—To investigate the reproducibility and sensitivity of the Zeiss retinal vessel analyser, a new method for the online determination of retinal vessel diameters in healthy subjects.
METHODS—Two model drugs were administered, a peripheral vasoconstrictor (the α receptor agonist phenylephrine) and a peripheral vasodilator (the nitric oxide donor sodium nitroprusside) in stepwise increasing doses. Nine healthy young subjects were studied in a placebo controlled double masked three way crossover design. Subjects received intravenous infusions of either placebo or stepwise increasing doses of phenylephrine (0.5, 1, or 2 µg/kg/min) or sodium nitroprusside (0.5, 1, or 2 µg/kg/min). Retinal vessel diameters were measured with the new Zeiss retinal vessel analyser. Retinal leucocyte velocity, flow, and density were measured with the blue field entoptic technique. The reproducibility of measurements was assessed with coefficients of variation and intraclass correlation coefficients.
RESULTS—Placebo and phenylephrine did not influence retinal haemodynamics, although the α receptor antagonist significantly increased blood pressure. Sodium nitroprusside induced a significant increase in retinal venous and arterial diameters (p<0.001 each), leucocyte density (p=0.001), and leucocyte flow (p=0.024) despite lowering blood pressure to a significant degree. For venous and arterial vessel size measurements short term coefficients of variation were 1.3% and 2.6% and intraclass correlation coefficients were 0.98 and 0.96, respectively. The sensitivity was between 3% and 5% for retinal veins and 5% and 7% for retinal arteries.
CONCLUSIONS—These data indicate that the Zeiss retinal vessel analyser is an accurate system for the assessment of retinal diameters in healthy subjects. In addition, nitric oxide appears to have a strong influence on retinal vascular tone.

 PMID:11049956

Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

NASA Technical Reports Server (NTRS)

Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

2003-01-01

Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

INTERNAL LIMITING MEMBRANE PEELING-DEPENDENT RETINAL STRUCTURAL CHANGES AFTER VITRECTOMY IN RHEGMATOGENOUS RETINAL DETACHMENT.

PubMed

Hisatomi, Toshio; Tachibana, Takashi; Notomi, Shoji; Koyanagi, Yoshito; Murakami, Yusuke; Takeda, Atsunobu; Ikeda, Yasuhiro; Yoshida, Shigeo; Enaida, Hiroshi; Murata, Toshinori; Sakamoto, Taiji; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2018-03-01

To examine retinal changes after vitrectomy with internal limiting membrane (ILM) peeling, we used 3-dimensional optical coherence tomography (3D-OCT) in rhegmatogenous retinal detachment cases. The 68 eyes from 67 patients with rhegmatogenous retinal detachment were studied, including 35 detached macula cases (51%) and 33 attached macula cases. Internal limiting membrane peeling was performed with fine forceps after brilliant blue G staining. The 3D-OCT images were obtained with volume-rendering technologies from cross-sectional OCT images. The 3D-OCT detected 45 eyes (66%) with ILM peeling-dependent retinal changes, including dissociated optic nerve fiber layer appearance, dimple sign, temporal macular thinning, ILM peeling area thinning, or forceps-related retinal thinning. The ILM peeled area was detectable in only 9 eyes with 3D-OCT, whereas it was undetectable in other 59 eyes. The dissociated optic nerve fiber layer appearance was detected in 8 of the total cases (12%), and dimple signs were observed in 14 cases (21%). Forceps-related thinning was also noted in eight cases (24%) of attached macula cases and in four cases (11%) of detached macula cases. No postoperative macular pucker was noted in the observational period. The 3D-OCT clearly revealed spatial and time-dependent retinal changes after ILM peeling. The changes occurred in 2 months and remained thereafter.

HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

PubMed

Olivares-González, Lorena; Martínez-Fernández de la Cámara, Cristina; Hervás, David; Millán, José María; Rodrigo, Regina

2018-05-01

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision due to rod and cone degeneration. Evidence suggests that an inappropriate oxygen level could contribute to its pathogenesis. Rod cell death could increase oxygen concentration, reduce hypoxia-inducible factor 1 (HIF-1α) and contribute to cone cell death. The purposes of this study were: 1) to analyze the temporal profile of HIF-1α, its downstream effectors VEGF, endothelin-1 (ET-1), iNOS, and glucose transporter 1 (GLUT1), and neuroinflammation in retinas of the murine model of rd10 ( retinal degeneration 10) mice with RP; 2) to study oxygen bioavailability in these retinas; and 3) to investigate how stabilizing HIF-1α proteins with dimethyloxaloglycine (DMOG), a prolyl hydroxylase inhibitor, affects retinal degeneration, neuroinflammation, and antioxidant response in rd10 mice. A generalized down-regulation of HIF-1α and its downstream targets was detected in parallel with reactive gliosis, suggesting high oxygen levels during retinal degeneration. At postnatal d 18, DMOG treatment reduced photoreceptor cell death and glial activation. In summary, retinas of rd10 mice seem to be exposed to a hyperoxic environment even at early stages of degeneration. HIF-1α stabilization could have a temporal neuroprotective effect on photoreceptor cell survival, glial activation, and antioxidant response at early stages of RP.-Olivares-González, L., Martínez-Fernández de la Cámara, C., Hervás, D., Millán, J. M., Rodrigo, R. HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

Modification of a Volume-Overload Heart Failure Model to Track Myocardial Remodeling and Device-Related Reverse Remodeling

PubMed Central

Tuzun, Egemen; Bick, Roger; Kadipasaoglu, Cihan; Conger, Jeffrey L.; Poindexter, Brian J.; Gregoric, Igor D.; Frazier, O. H.; Towbin, Jeffrey A.; Radovancevic, Branislav

2011-01-01

Purpose. To provide an ovine model of ventricular remodeling and reverse remodeling by creating congestive heart failure (CHF) and then treating it by implanting a left ventricular assist device (LVAD). Methods. We induced volume-overload heart failure in 2 sheep; 20 weeks later, we implanted an LVAD and assessed recovery 11 weeks thereafter. We examined changes in histologic and hemodynamic data and levels of cellular markers of CHF. Results. After CHF induction, we found increases in LV end-diastolic pressure, LV systolic and diastolic dimensions, wall thickness, left atrial diameter, and atrial natriuretic protein (ANP) and endothelin-1 (ET-1) levels; β-adrenergic receptor (BAR) and dystrophin expression decreased markedly. Biopsies confirmed LV remodeling. After LVAD support, LV systolic and diastolic dimensions, wall thickness, and mass, and ANP and ET-1 levels decreased. Histopathologic and hemodynamic markers improved, and BAR and dystrophin expression normalized. Conclusions. We describe a successful sheep model for ventricular and reverse remodeling. PMID:22347659

Focal posterior pole viral retinitis.

PubMed

Hazirolan, Dicle; Sungur, Gulten; Demir, Necati; Kasim, Remzi; Duman, Sunay

2010-01-01

To describe the clinical features of an atypical form of viral retinitis in immunocompetent patients. This was a retrospective noncomparative case series. The charts of 8 patients diagnosed with and treated for focal posterior viral retinitis were reviewed. Clinical and demographic features were evaluated. All the patients had extensive laboratory tests, fundus fluorescein angiography, optical coherence tomography of macula, and polymerase chain reaction of vitreous. All the patients were referred to our Uveitis Service from other hospitals, as their uveitis symptoms deteriorated in spite of treatment. The mean age of 4 male and 4 female patients was 32.1 years (range, 22-42 years). The mean follow-up period was 10 months (range, 6-18 months). All of the patients had unilateral disease. Polymerase chain reaction analysis of vitreous specimen was positive for herpes simplex virus-1 in 5 patients and varicella zoster virus in 3 patients. Retinitis resolved after systemic acyclovir treatment in all patients. Viral etiology must be borne in mind in the differential diagnosis of atypical retinitis. It can be a milder form of viral retinitis like focal viral retinitis, as mentioned in this study. The prognosis of this disease is better than the other forms of necrotizing retinopathies involving a larger area of retina.

Filling in the retinal image

NASA Technical Reports Server (NTRS)

Larimer, James; Piantanida, Thomas

1990-01-01

The optics of the eye form an image on a surface at the back of the eyeball called the retina. The retina contains the photoreceptors that sample the image and convert it into a neural signal. The spacing of the photoreceptors in the retina is not uniform and varies with retinal locus. The central retinal field, called the macula, is densely packed with photoreceptors. The packing density falls off rapidly as a function of retinal eccentricity with respect to the macular region and there are regions in which there are no photoreceptors at all. The retinal regions without photoreceptors are called blind spots or scotomas. The neural transformations which convert retinal image signals into percepts fills in the gaps and regularizes the inhomogeneities of the retinal photoreceptor sampling mosaic. The filling-in mechamism plays an important role in understanding visual performance. The filling-in mechanism is not well understood. A systematic collaborative research program at the Ames Research Center and SRI in Menlo Park, California, was designed to explore this mechanism. It was shown that the perceived fields which are in fact different from the image on the retina due to filling-in, control some aspects of performance and not others. Researchers have linked these mechanisms to putative mechanisms of color coding and color constancy.

Exploring photoreceptor reflectivity via multimodal imaging of outer retinal tubulation in advanced age-related macular degeneration

PubMed Central

Litts, Katie M.; Wang, Xiaolin; Clark, Mark E.; Owsley, Cynthia; Freund, K. Bailey; Curcio, Christine A.; Zhang, Yuhua

2016-01-01

Purpose To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO). Methods Four eyes of 4 subjects with advanced AMD underwent color fundus photography, infrared reflectance imaging, SD-OCT, and AOSLO with a high-resolution research instrument. ORT was identified in closely spaced (11 μm) SD-OCT volume scans. Results ORT in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by AOSLO was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors. Conclusion Lack of ORT cone reflectivity by AOSLO indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in OCT. PMID:27584549

Expression Profiling Analysis Reveals Key MicroRNA–mRNA Interactions in Early Retinal Degeneration in Retinitis Pigmentosa

PubMed Central

Anasagasti, Ander; Ezquerra-Inchausti, Maitane; Barandika, Olatz; Muñoz-Culla, Maider; Caffarel, María M.; Otaegui, David; López de Munain, Adolfo

2018-01-01

Purpose The aim of this study was to identify differentially expressed microRNAs (miRNAs) that might play an important role in the etiology of retinal degeneration in a genetic mouse model of retinitis pigmentosa (rd10 mice) at initial stages of the disease. Methods miRNAs–mRNA interaction networks were generated for analysis of biological pathways involved in retinal degeneration. Results Of more than 1900 miRNAs analyzed, we selected 19 miRNAs on the basis of (1) a significant differential expression in rd10 retinas compared with control samples and (2) an inverse expression relationship with predicted mRNA targets involved in biological pathways relevant to retinal biology and/or degeneration. Seven of the selected miRNAs have been associated with retinal dystrophies, whereas, to our knowledge, nine have not been previously linked to any disease. Conclusions This study contributes to our understanding of the etiology and progression of retinal degeneration. PMID:29847644

Novel method for edge detection of retinal vessels based on the model of the retinal vascular network and mathematical morphology

NASA Astrophysics Data System (ADS)

Xu, Lei; Zheng, Xiaoxiang; Zhang, Hengyi; Yu, Yajun

1998-09-01

Accurate edge detection of retinal vessels is a prerequisite for quantitative analysis of subtle morphological changes of retinal vessels under different pathological conditions. A novel method for edge detection of retinal vessels is presented in this paper. Methods: (1) Wavelet-based image preprocessing. (2) The signed edge detection algorithm and mathematical morphological operation are applied to get the approximate regions that contain retinal vessels. (3) By convolving the preprocessed image with a LoG operator only on the detected approximate regions of retinal vessels, followed by edges refining, clear edge maps of the retinal vessels are fast obtained. Results: A detailed performance evaluation together with the existing techniques is given to demonstrate the strong features of our method. Conclusions: True edge locations of retinal vessels can be fast detected with continuous structures of retinal vessels, less non- vessel segments left and insensitivity to noise. The method is also suitable for other application fields such as road edge detection.

Comprehensive analysis of mouse retinal mononuclear phagocytes.

PubMed

Lückoff, Anika; Scholz, Rebecca; Sennlaub, Florian; Xu, Heping; Langmann, Thomas

2017-06-01

The innate immune system is activated in a number of degenerative and inflammatory retinal disorders such as age-related macular degeneration (AMD). Retinal microglia, choroidal macrophages, and recruited monocytes, collectively termed 'retinal mononuclear phagocytes', are critical determinants of ocular disease outcome. Many publications have described the presence of these cells in mouse models for retinal disease; however, only limited aspects of their behavior have been uncovered, and these have only been uncovered using a single detection method. The workflow presented here describes a comprehensive analysis strategy that allows characterization of retinal mononuclear phagocytes in vivo and in situ. We present standardized working steps for scanning laser ophthalmoscopy of microglia from MacGreen reporter mice (mice expressing the macrophage colony-stimulating factor receptor GFP transgene throughout the mononuclear phagocyte system), quantitative analysis of Iba1-stained retinal sections and flat mounts, CD11b-based retinal flow cytometry, and qRT-PCR analysis of key microglia markers. The protocol can be completed within 3 d, and we present data from retinas treated with laser-induced choroidal neovascularization (CNV), bright white-light exposure, and Fam161a-associated inherited retinal degeneration. The assays can be applied to any of the existing mouse models for retinal disorders and may be valuable for documenting immune responses in studies for immunomodulatory therapies.

Clinically undetected retinal breaks causing retinal detachment: A review of options for management.

PubMed

Gupta, Deepak; Ching, Jared; Tornambe, Paul E

2017-08-12

The successful detection of retinal breaks is a critical step in rhegmatogenous retinal detachment surgery in order to prevent persistent/recurrent retinal detachments. Not all retinal breaks causing retinal detachments are obvious. Retinal breaks may be obscured by opacities that are either anterior segment related, lens related, or posterior segment related. Rules to identify breaks based on subretinal fluid configuration are more difficult to apply in pseudophakic, aphakic, and scleral buckle encircled eyes-and in eyes with repeat detachments and those with proliferative vitreoretinopathy. Exudative detachments exhibit characteristic features and must be ruled out. A thorough clinical examination preoperatively is important even if a vitrectomy is planned. We review the incidence and causes of undetected breaks, along with preoperative/clinical issues that may hinder break detection. We review the literature with respect to investigative approaches and techniques that are available to the vitreoretinal surgeon when primary breaks remain clinically undetected during the preoperative examination. We broadly divide the surgical approaches into ones where the surgeon utilizes techniques to pursue actively a search for breaks versus adopting a purely speculative approach. Advantages and disadvantages of various techniques are appraised. Intuitively one might argue that an encircling scleral buckle combined with vitrectomy would give higher single operation success than pars plana vitrectomy alone because "undetected" retinal breaks would be addressed by a 360° plombage. We could not confirm this concept. Newer techniques, such as pars plana vitrectomy augmented with dye extrusion or endoscopic-assisted pars plana vitrectomy, show encouraging results. Technological advances such as intraoperative optical coherence tomography will also help to broaden the vitreoretinal surgeon's armamentarium. At this time, there is no gold standard in terms of the recommended

Effects of nucleosome stability on remodeler-catalyzed repositioning

NASA Astrophysics Data System (ADS)

Morgan, Aaron M.; LeGresley, Sarah E.; Briggs, Koan; Al-Ani, Gada; Fischer, Christopher J.

2018-03-01

Chromatin remodelers are molecular motors that play essential roles in the regulation of nucleosome positioning and chromatin accessibility. These machines couple the energy obtained from the binding and hydrolysis of ATP to the mechanical work of manipulating chromatin structure through processes that are not completely understood. Here we present a quantitative analysis of nucleosome repositioning by the imitation switch (ISWI) chromatin remodeler and demonstrate that nucleosome stability significantly impacts the observed activity. We show how DNA damage induced changes in the affinity of DNA wrapping within the nucleosome can affect ISWI repositioning activity and demonstrate how assay-dependent limitations can bias studies of nucleosome repositioning. Together, these results also suggest that some of the diversity seen in chromatin remodeler activity can be attributed to the variations in the thermodynamics of interactions between the remodeler, the histones, and the DNA, rather than reflect inherent properties of the remodeler itself.

Control of bone remodelling by applied dynamic loads

NASA Technical Reports Server (NTRS)

Lanyon, L. E.; Rubin, C. T.

1984-01-01

The data showing the relationship between bone mass and peak strain magnitude prepared and submitted for publication. The data from experiments relating remodelling activity with static or dynamic loads were prepared and submitted for publication. Development of programs to relate the location of remodelling activity with he natural and artificial dynamic strain distributions continued. Experiments on the effect of different strain rates on the remodelling response continued.

OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN CYTOMEGALOVIRUS RETINITIS: A Longitudinal Study.

PubMed

Invernizzi, Alessandro; Agarwal, Aniruddha; Ravera, Vittoria; Oldani, Marta; Staurenghi, Giovanni; Viola, Francesco

2018-01-01

To evaluate the vitreal, retinal, and choroidal features using spectral domain optical coherence tomography (SD-OCT) in eyes affected by cytomegalovirus (CMV) retinitis. Patients diagnosed with either active or inactive CMV retinitis were included in the study. Complete ophthalmic examination, serial color fundus photography, and SD-OCT (with and without enhanced depth imaging function) were performed for all the subjects at baseline and follow-up visits. The SD-OCT images were analyzed by two independent graders to evaluate the structural changes in areas of CMV retinitis. Prevalence data for vitreal, retinal, and choroidal SD-OCT features were collected. Twelve eyes from 9 patients (6 males, mean age: 52.7 ± 10.3 years) were enrolled. Nine eyes were diagnosed with active CMV retinitis at baseline. Active disease SD-OCT characteristic findings included nebulous vitritis (100%), posterior hyaloid thickening (83.3%), epiretinal membrane (100%), and retinal swelling (100%). Two distinct patterns of chorioretinal involvement were observed in active retinitis: 1) full-thickness retinitis (Full thickness retinitis) (n = 7 eyes) with choriocapillaris alterations and retinal pigment epithelial thickening and 2) cavernous retinitis (n = 3 eyes) characterized by inner retinal hyperreflectivity, large empty spaces in outer nuclear layer, and bridges of retinal tissue but retinal pigment epithelium and choriocapillaris sparing. Patients with cavernous retinitis develop retinal detachment during follow-up. Eyes with Full thickness retinitis developed choriocapillaris atrophy and choroidal thinning and retinal scars as the lesions healed. There are two distinct patterns of chorioretinal involvement in CMV retinitis. SD-OCT is a useful tool in the diagnosis, management, and prediction of the outcome of CMV retinitis.

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment Update

PubMed Central

Lee, Christine; Tu, Hong Anh; Wells, David; Holubowich, Corinne

2017-01-01

Background Retinitis pigmentosa is a group of inherited disorders characterized by the degeneration of the photoreceptors in the retina, resulting in progressive vision loss. The Argus II system is designed to restore partial functional vision in patients with profound vision loss from advanced retinitis pigmentosa. At present, it is the only treatment option approved by Health Canada for this patient population. In June 2016, Health Quality Ontario published a health technology assessment of the Argus II retinal prosthesis system for patients with advanced retinitis pigmentosa. Based on that assessment, the Ontario Health Technology Advisory Committee recommended against publicly funding the Argus II system for this population. It also recommended that Health Quality Ontario re-evaluate the evidence in 1 year. The objective of this report was to examine new evidence published since the 2016 health technology assessment. Methods We completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, and patient preferences related to the Argus II system. We performed a systematic literature search for studies published since the 2016 Argus II health technology assessment. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care, and we calculated incremental cost-effectiveness ratios over a 20-year time horizon. We also conducted a five-year budget impact analysis. Finally, we interviewed people with retinitis pigmentosa about their lived experience with vision loss, and with the Argus II system. Results Four publications from one multicentre international study were included in the clinical review. Patients showed significant improvements in visual function and functional outcomes with the Argus II system, and these outcomes were sustained up to a 5-year follow-up (moderate quality of evidence). The safety profile was generally acceptable. In

Extensive Intestinal Resection Triggers Behavioral Adaptation, Intestinal Remodeling and Microbiota Transition in Short Bowel Syndrome

PubMed Central

Mayeur, Camille; Gillard, Laura; Le Beyec, Johanne; Bado, André; Joly, Francisca; Thomas, Muriel

2016-01-01

Extensive resection of small bowel often leads to short bowel syndrome (SBS). SBS patients develop clinical mal-absorption and dehydration relative to the reduction of absorptive area, acceleration of gastrointestinal transit time and modifications of the gastrointestinal intra-luminal environment. As a consequence of severe mal-absorption, patients require parenteral nutrition (PN). In adults, the overall adaptation following intestinal resection includes spontaneous and complex compensatory processes such as hyperphagia, mucosal remodeling of the remaining part of the intestine and major modifications of the microbiota. SBS patients, with colon in continuity, harbor a specific fecal microbiota that we called “lactobiota” because it is enriched in the Lactobacillus/Leuconostoc group and depleted in anaerobic micro-organisms (especially Clostridium and Bacteroides). In some patients, the lactobiota-driven fermentative activities lead to an accumulation of fecal d/l-lactates and an increased risk of d-encephalopathy. Better knowledge of clinical parameters and lactobiota characteristics has made it possible to stratify patients and define group at risk for d-encephalopathy crises. PMID:27681910

Valve sparing aortic replacement - root remodeling.

PubMed

Lausberg, Henning F; Schäfers, Hans-Joachim

2006-01-01

Aortic root remodeling restores aortic root geometry and improves valve competence. We have used this technique whenever aorto-ventricular diameter is preserved. The operative technique is detained in this presentation. As a result of our 10-year experience with root remodeling we propose this operation as a reproducible option for patients with dilatation of the aortic root.

Survey on diagnosis of diseases from retinal images

NASA Astrophysics Data System (ADS)

Das, Sneha; Malathy, C.

2018-04-01

Retina is a thin membranous layer of tissue that occupies at the back of the eye which provides central vision needed for daily routines. Identifying retinal diseases at the early stage is a challenging task since healthy retina is required for central vision. Several retinal diseases affect the eye such as retinal tear, retinal detachment, glaucoma, macular hole and macular degeneration etc. These maladies will encounter a secondary growth in the close future as the age of the person increases. A survey is made which tells about the diagnosis of the retinal diseases from the retinal images using machine learning techniques.

Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodeling.

PubMed

Stolp, Bettina; Abraham, Libin; Rudolph, Jochen M; Fackler, Oliver T

2010-04-01

Nef is an accessory protein and pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) which elevates virus replication in vivo. We recently described for HIV type 1(SF2) (HIV-1(SF2)) the potent interference of Nef with T-lymphocyte chemotaxis via its association with the cellular kinase PAK2. Mechanistic analysis revealed that this interaction results in deregulation of the actin-severing factor cofilin and thus blocks the chemokine-mediated actin remodeling required for cell motility. However, the efficiency of PAK2 association is highly variable among Nef proteins from different lentiviruses, prompting us to evaluate the conservation of this actin-remodeling/cofilin-deregulating mechanism. Based on the analysis of a total of 17 HIV-1, HIV-2, and SIV Nef proteins, we report here that inhibition of chemokine-induced actin remodeling as well as inactivation of cofilin are strongly conserved activities of lentiviral Nef proteins. Of note, even for Nef variants that display only marginal PAK2 association in vitro, these activities require the integrity of a PAK2 recruitment motif and the presence of endogenous PAK2. Thus, reduced in vitro affinity to PAK2 does not indicate limited functionality of Nef-PAK2 complexes in intact HIV-1 host cells. These results establish hijacking of PAK2 for deregulation of cofilin and inhibition of triggered actin remodeling as a highly conserved function of lentiviral Nef proteins, supporting the notion that PAK2 association may be critical for Nef's activity in vivo.

Retinal Effects Of Blue Light Exposure

NASA Astrophysics Data System (ADS)

Ham, William T.; Mueller, Harold A.; Ruffolo, J. J.

1980-10-01

Recent research has shown that blue light exposure is an important factor in certain types of retinal injury. The mammalian ocular media transmits the spectral band 400-1400 nm to the retina. The short wavelengths (400-550 nm) produce a photochemical or actinic type of damage, while the longer wavelengths (550-1400 nm) produce thermal damage. Distinction between the two types of retinal damage are discussed briefly and the importance of the blue light effect for solar retinitis and eclipse blindness is emphasized. The significance of blue light retinal injury is summarized for various environmental and occupational exposures.

Relation of retinal blood flow and retinal oxygen extraction during stimulation with diffuse luminance flicker

PubMed Central

Palkovits, Stefan; Lasta, Michael; Told, Reinhard; Schmidl, Doreen; Werkmeister, René; Cherecheanu, Alina Popa; Garhöfer, Gerhard; Schmetterer, Leopold

2015-01-01

Cerebral and retinal blood flow are dependent on local neuronal activity. Several studies quantified the increase in cerebral blood flow and oxygen consumption during activity. In the present study we investigated the relation between changes in retinal blood flow and oxygen extraction during stimulation with diffuse luminance flicker and the influence of breathing gas mixtures with different fractions of O2 (FiO2; 100% 15% and 12%). Twenty-four healthy subjects were included. Retinal blood flow was studied by combining measurement of vessel diameters using the Dynamic Vessel Analyser with measurements of blood velocity using laser Doppler velocimetry. Oxygen saturation was measured using spectroscopic reflectometry and oxygen extraction was calculated. Flicker stimulation increased retinal blood flow (57.7 ± 17.8%) and oxygen extraction (34.6 ± 24.1%; p < 0.001 each). During 100% oxygen breathing the response of retinal blood flow and oxygen extraction was increased (p < 0.01 each). By contrast, breathing gas mixtures with 12% and 15% FiO2 did not alter flicker–induced retinal haemodynamic changes. The present study indicates that at a comparable increase in blood flow the increase in oxygen extraction in the retina is larger than in the brain. During systemic hyperoxia the blood flow and oxygen extraction responses to neural stimulation are augmented. The underlying mechanism is unknown. PMID:26672758

Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

PubMed

Tanaka, Leonardo Y; Laurindo, Francisco R M

2017-08-01

Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases. Copyright © 2017 Elsevier Inc. All

Oleoyl serine, an endogenous N-acyl amide, modulates bone remodeling and mass

PubMed Central

Smoum, Reem; Bar, Arik; Tan, Bo; Milman, Garry; Attar-Namdar, Malka; Ofek, Orr; Stuart, Jordyn M.; Bajayo, Alon; Tam, Joseph; Kram, Vardit; O'Dell, David; Walker, Michael J.; Bradshaw, Heather B.; Bab, Itai; Mechoulam, Raphael

2010-01-01

Bone mass is determined by a continuous remodeling process, whereby the mineralized matrix is being removed by osteoclasts and subsequently replaced with newly formed bone tissue produced by osteoblasts. Here we report the presence of endogenous amides of long-chain fatty acids with amino acids or with ethanolamine (N-acyl amides) in mouse bone. Of these compounds, N-oleoyl-l-serine (OS) had the highest activity in an osteoblast proliferation assay. In these cells, OS triggers a Gi-protein-coupled receptor and Erk1/2. It also mitigates osteoclast number by promoting osteoclast apoptosis through the inhibition of Erk1/2 phosphorylation and receptor activator of nuclear-κB ligand (RANKL) expression in bone marrow stromal cells and osteoblasts. In intact mice, OS moderately increases bone volume density mainly by inhibiting bone resorption. However, in a mouse ovariectomy (OVX) model for osteoporosis, OS effectively rescues bone loss by increasing bone formation and markedly restraining bone resorption. The differential effect of exogenous OS in the OVX vs. intact animals is apparently a result of an OVX-induced decrease in skeletal OS levels. These data show that OS is a previously unexplored lipid regulator of bone remodeling. It represents a lead to antiosteoporotic drug discovery, advantageous to currently available therapies, which are essentially either proformative or antiresorptive. PMID:20876113

Remodeling of intermediate metabolism in the diatom Phaeodactylum tricornutum under nitrogen stress

PubMed Central

Levitan, Orly; Dinamarca, Jorge; Zelzion, Ehud; Lun, Desmond S.; Guerra, L. Tiago; Kim, Min Kyung; Kim, Joomi; Van Mooy, Benjamin A. S.; Bhattacharya, Debashish; Falkowski, Paul G.

2015-01-01

Diatoms are unicellular algae that accumulate significant amounts of triacylglycerols as storage lipids when their growth is limited by nutrients. Using biochemical, physiological, bioinformatics, and reverse genetic approaches, we analyzed how the flux of carbon into lipids is influenced by nitrogen stress in a model diatom, Phaeodactylum tricornutum. Our results reveal that the accumulation of lipids is a consequence of remodeling of intermediate metabolism, especially reactions in the tricarboxylic acid and the urea cycles. Specifically, approximately one-half of the cellular proteins are cannibalized; whereas the nitrogen is scavenged by the urea and glutamine synthetase/glutamine 2-oxoglutarate aminotransferase pathways and redirected to the de novo synthesis of nitrogen assimilation machinery, simultaneously, the photobiological flux of carbon and reductants is used to synthesize lipids. To further examine how nitrogen stress triggers the remodeling process, we knocked down the gene encoding for nitrate reductase, a key enzyme required for the assimilation of nitrate. The strain exhibits 40–50% of the mRNA copy numbers, protein content, and enzymatic activity of the wild type, concomitant with a 43% increase in cellular lipid content. We suggest a negative feedback sensor that couples photosynthetic carbon fixation to lipid biosynthesis and is regulated by the nitrogen assimilation pathway. This metabolic feedback enables diatoms to rapidly respond to fluctuations in environmental nitrogen availability. PMID:25548193

Acute retinal ischemia inhibits endothelium-dependent nitric oxide-mediated dilation of retinal arterioles via enhanced superoxide production.

PubMed

Hein, Travis W; Ren, Yi; Potts, Luke B; Yuan, Zhaoxu; Kuo, Enoch; Rosa, Robert H; Kuo, Lih

2012-01-03

Because retinal vascular disease is associated with ischemia and increased oxidative stress, the vasodilator function of retinal arterioles was examined after retinal ischemia induced by elevated intraocular pressure (IOP). The role of superoxide anions in the development of vascular dysfunction was assessed. IOP was increased and maintained at 80 to 90 mm Hg for 30, 60, or 90 minutes by infusing saline into the anterior chamber of a porcine eye. The fellow eye with normal IOP (10-20 mm Hg) served as control. In some pigs, superoxide dismutase mimetic TEMPOL (1 mM) or vehicle (saline) was injected intravitreally before IOP elevation. After enucleation, retinal arterioles were isolated and pressurized without flow for functional analysis by recording diameter changes using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production in isolated retinal arterioles. Isolated retinal arterioles developed stable basal tone and the vasodilations to endothelium-dependent nitric oxide (NO)-mediated agonists bradykinin and L-lactate were significantly reduced only by 90 minutes of ischemia. However, vasodilation to endothelium-independent NO donor sodium nitroprusside was unaffected after all time periods of ischemia. DHE staining showed that 90 minutes of ischemia significantly increased superoxide levels in retinal arterioles. Intravitreal injection of membrane-permeable radical scavenger but not vehicle before ischemia prevented elevation of vascular superoxide and preserved bradykinin-induced dilation. Endothelium-dependent NO-mediated dilation of retinal arterioles is impaired by 90 minutes of ischemia induced by elevated IOP. The inhibitory effect appears to be mediated by the alteration of NO signaling via vascular superoxide.

Transcorneal Electrical Stimulation Therapy for Retinal Disease

ClinicalTrials.gov

2012-05-03

Retinitis Pigmentosa; Macula Off; Primary Open Angle Glaucoma; Hereditary Macular Degeneration; Treated Retina Detachment; Retinal Artery Occlusion; Retinal Vein Occlusion; Non-Arthritic-Anterior-Ischemic Optic-Neuropathy; Hereditary Autosomal Dominant Optic Atrophy; Dry Age Related Macular Degeneration; Ischemic Macula Edema

Inherited Retinal Degenerative Clinical Trial Network

DTIC Science & Technology

2009-10-01

ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network

CHD3 and CHD4 recruitment and chromatin remodeling activity at DNA breaks is promoted by early poly(ADP-ribose)-dependent chromatin relaxation.

PubMed

Smith, Rebecca; Sellou, Hafida; Chapuis, Catherine; Huet, Sébastien; Timinszky, Gyula

2018-05-04

One of the first events to occur upon DNA damage is the local opening of the compact chromatin architecture, facilitating access of repair proteins to DNA lesions. This early relaxation is triggered by poly(ADP-ribosyl)ation by PARP1 in addition to ATP-dependent chromatin remodeling. CHD4 recruits to DNA breaks in a PAR-dependent manner, although it lacks any recognizable PAR-binding domain, and has the ability to relax chromatin structure. However, its role in chromatin relaxation at the site of DNA damage has not been explored. Using a live cell fluorescence three-hybrid assay, we demonstrate that the recruitment of CHD4 to DNA damage, while being poly(ADP-ribosyl)ation-dependent, is not through binding poly(ADP-ribose). Additionally, we show that CHD3 is recruited to DNA breaks in the same manner as CHD4 and that both CHD3 and CHD4 play active roles in chromatin remodeling at DNA breaks. Together, our findings reveal a two-step mechanism for DNA damage induced chromatin relaxation in which PARP1 and the PAR-binding remodeler activities of Alc1/CHD1L induce an initial chromatin relaxation phase that promotes the subsequent recruitment of CHD3 and CHD4 via binding to DNA for further chromatin remodeling at DNA breaks.

C/EBPβ and Nuclear Factor of Activated T Cells Differentially Regulate Adamts-1 Induction by Stimuli Associated with Vascular Remodeling

PubMed Central

Oller, Jorge; Alfranca, Arántzazu; Méndez-Barbero, Nerea; Villahoz, Silvia; Lozano-Vidal, Noelia; Martín-Alonso, Mara; Arroyo, Alicia G.; Escolano, Amelia; Armesilla, Angel Luis

2015-01-01

Emerging evidence indicates that the metalloproteinase Adamts-1 plays a significant role in the pathophysiology of vessel remodeling, but little is known about the signaling pathways that control Adamts-1 expression. We show that vascular endothelial growth factor (VEGF), angiotensin-II, interleukin-1β, and tumor necrosis factor α, stimuli implicated in pathological vascular remodeling, increase Adamts-1 expression in endothelial and vascular smooth muscle cells. Analysis of the intracellular signaling pathways implicated in this process revealed that VEGF and angiotensin-II upregulate Adamts-1 expression via activation of differential signaling pathways that ultimately promote functional binding of the NFAT or C/EBPβ transcription factors, respectively, to the Adamts-1 promoter. Infusion of mice with angiotensin-II triggered phosphorylation and nuclear translocation of C/EBPβ proteins in aortic cells concomitantly with an increase in the expression of Adamts-1, further underscoring the importance of C/EBPβ signaling in angiotensin-II-induced upregulation of Adamts-1. Similarly, VEGF promoted NFAT activation and subsequent Adamts-1 induction in aortic wall in a calcineurin-dependent manner. Our results demonstrate that Adamts-1 upregulation by inducers of pathological vascular remodeling is mediated by specific signal transduction pathways involving NFAT or C/EBPβ transcription factors. Targeting of these pathways may prove useful in the treatment of vascular disease. PMID:26217013

Pilot Study of Optical Coherence Tomography Measurement of Retinal Blood Flow in Retinal and Optic Nerve Diseases

PubMed Central

Wang, Yimin; Fawzi, Amani A.; Varma, Rohit; Sadun, Alfredo A.; Zhang, Xinbo; Tan, Ou; Izatt, Joseph A.

2011-01-01

Purpose. To investigate blood flow changes in retinal and optic nerve diseases with Doppler Fourier domain optical coherence tomography (OCT). Methods. Sixty-two participants were divided into five groups: normal, glaucoma, nonarteritic ischemic optic neuropathy (NAION), treated proliferative diabetic retinopathy (PDR), and branch retinal vein occlusion (BRVO). Doppler OCT was used to scan concentric circles of 3.4- and 3.75-mm diameters around the optic nerve head. Flow in retinal veins was calculated from the OCT velocity profiles. Arterial and venous diameters were measured from OCT Doppler and reflectance images. Results. Total retinal blood flow in normal subjects averaged 47.6 μL/min. The coefficient of variation of repeated measurements was 11% in normal eyes and 14% in diseased eyes. Eyes with glaucoma, NAION, treated PDR, and BRVO had significantly decreased retinal blood flow compared with normal eyes (P < 0.001). In glaucoma patients, the decrease in blood flow was highly correlated with the severity of visual field loss (P = 0.003). In NAION and BRVO patients, the hemisphere with more severe disease also had lower blood flow. Conclusions. Doppler OCT retinal blood flow measurements showed good repeatability and excellent correlation with visual field and clinical presentations. This approach could enhance our understanding of retinal and optic nerve diseases and facilitate the development of new therapies. PMID:21051715

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

PubMed Central

Damle‐Vartak, Amruta; Richter, Beate; Dirsch, Olaf; Dahmen, Uta; Hammad, Seddik

2016-01-01

Cholestasis is a common complication in liver diseases that triggers a proliferative response of the biliary tree. Bile duct ligation (BDL) is a frequently used model of cholestasis in rodents. To determine which changes occur in the three‐dimensional (3D) architecture of the interlobular bile duct during cholestasis, we used 3D confocal imaging, surface reconstructions, and automated image quantification covering a period up to 28 days after BDL. We show a highly reproducible sequence of interlobular duct remodeling, where cholangiocyte proliferation initially causes corrugation of the luminal duct surface, leading to an approximately five‐fold increase in surface area. This is analogous to the function of villi in the intestine or sulci in the brain, where an expansion of area is achieved within a restricted volume. The increase in surface area is further enhanced by duct branching, branch elongation, and loop formation through self‐joining, whereby an initially relatively sparse mesh surrounding the portal vein becomes five‐fold denser through elongation, corrugation, and ramification. The number of connections between the bile duct and the lobular bile canalicular network by the canals of Hering decreases proportionally to the increase in bile duct length, suggesting that no novel connections are established. The diameter of the interlobular bile duct remains constant after BDL, a response that is qualitatively distinct from that of large bile ducts, which tend to enlarge their diameters. Therefore, volume enhancement is only due to net elongation of the ducts. Because curvature and tortuosity of the bile duct are unaltered, this enlargement of the biliary tree is caused by branching and not by convolution. Conclusion: BDL causes adaptive remodeling that aims at optimizing the intraluminal surface area by way of corrugation and branching. (Hepatology 2016;63:951–964) PMID:26610202

ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

PubMed Central

Hayreh, Sohan Singh

2011-01-01

The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual

Safety of iPhone retinal photography.

PubMed

Hong, Sheng Chiong; Wynn-Williams, Giles; Wilson, Graham

2017-04-01

With the advancement in mobile technology, smartphone retinal photography is becoming a popular practice. However, there is limited information about the safety of the latest smartphones used for retinal photography. This study aims to determine the photobiological risk of iPhone 6 and iPhone 6 plus when used in conjunction with a 20Diopter condensing lens for retinal photography. iPhone 6 and iPhone 6 plus (Apple, Cupertino, CA) were used in this study. The geometrical setup of the study was similar to the indirect ophthalmoscopy technique. The phone was set up at one end of the bench with its flash turned on at maximal brightness; a 20 Dioptre lens was placed 15 cm away from the phone. The light that passes through the lens was measured with a spectroradiometer and an illuminance probe at the other end to determine the spectral profile, spatial irradiance, radiant power emitted by the phone's flash. Trigonometric and lens formula were applied to determine the field of view and retinal surface in order to determine the weighted retinal irradiance and weighted retinal radiant exposure. Taking ocular transmission and the distribution of the beam's spatial irradiance into account, the weighted retinal irradiance is 1.40 mW/cm 2 and the weighted retinal radiant exposure is 56.25 mJ/cm 2 . The peak weighted foveal irradiance is 1.61 mW/cm 2 . Our study concluded that the photobiological risk posed by iPhone 6 indirect ophthalmoscopy was at least 1 order of magnitude below the safety limits set by the ISO15004-2.2.

Minireview: Fibronectin in retinal disease.

PubMed

Miller, Charles G; Budoff, Greg; Prenner, Jonathan L; Schwarzbauer, Jean E

2017-01-01

Retinal fibrosis, characterized by dysregulation of extracellular matrix (ECM) protein deposition by retinal endothelial cells, pigment epithelial cells, and other resident cell-types, is a unifying feature of several common retinal diseases. Fibronectin is an early constituent of newly deposited ECM and serves as a template for assembly of other ECM proteins, including collagens. Under physiologic conditions, fibronectin is found in all layers of Bruch's membrane. Proliferative vitreoretinopathy (PVR), a complication of retinal surgery, is characterized by ECM accumulation. Among the earliest histologic manifestations of diabetic retinopathy (DR) is capillary basement membrane thickening, which occurs due to perturbations in ECM homeostasis. Neovascularization, the hallmark of late stage DR as well as exudative age-related macular degeneration (AMD), involves ECM assembly as a scaffold for the aberrant new vessel architecture. Rodent models of retinal injury demonstrate a key role for fibronectin in complications characteristic of PVR, including retinal detachment. In mouse models of DR, reducing fibronectin gene expression has been shown to arrest the accumulation of ECM in the capillary basement membrane. Alterations in matrix metalloproteinase activity thought to be important in the pathogenesis of AMD impact the turnover of fibronectin matrix as well as collagens. Growth factors involved in PVR, AMD, and DR, such as PDGF and TGFβ, are known to stimulate fibronectin matrix assembly. A deeper understanding of how pathologic ECM deposition contributes to disease progression may help to identify novel targets for therapeutic intervention. © 2016 by the Society for Experimental Biology and Medicine.

Clinical Outcome of Retinal Vasculitis and Predictors for Prognosis of Ischemic Retinal Vasculitis.

PubMed

Sharief, Lazha; Lightman, Sue; Blum-Hareuveni, Tamar; Bar, Asaf; Tomkins-Netzer, Oren

2017-05-01

To determine factors affecting the visual outcome in eyes with retinal vasculitis and the rate of neovascularization relapse in ischemic vasculitis. Retrospective cohort study. We reviewed 1169 uveitis patients from Moorfields Eye Hospital, London, UK. Retinal vasculitis was observed in 236 eyes (121 ischemic, 115 nonischemic) that were compared with a control group (1022 eyes) with no retinal vasculitis. Ultra-widefield fluorescein angiography images were obtained in 63 eyes with ischemic vasculitis to quantify area of nonperfusion measured as ischemic index. The risk of vision loss was significantly more in the retinal vasculitis compared with the non-vasculitis group (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.24-2.25, P = .001). Retinal vasculitis had twice the risk of macular edema compared to the non-vasculitis group. Macular ischemia increased the risk of vision loss in vasculitis eyes by 4.4 times. The use of systemic prednisolone in eyes with vasculitis was associated with a reduced risk of vision loss (HR 0.36, 95% CI 0.15-0.82, P = .01). Laser photocoagulation was administered in 75 eyes (62.0%), out of which 29 (38.1%) had new vessel relapse and required additional laser treatment. The median ischemic index was 25.8% (interquartile range 10.2%-46%). Ischemia involving ≥2 quadrants was associated with increased risk of new vessel formation (HR 2.7, 95% CI 1.3-5.5, P = .003). Retinal vasculitis is associated with an increased risk of vision loss, mainly secondary to macular ischemia, and has a higher risk of macular edema compared to eyes with no vasculitis. Ischemia involving ≥2 quadrants is a risk factor for new vessel formation. Copyright © 2017 Elsevier Inc. All rights reserved.

Reprogramming retinal neurons and standardized quantification of their differentiation in 3-dimensional retinal cultures

PubMed Central

Hiler, Daniel J.; Barabas, Marie E.; Griffiths, Lyra M.; Dyer, Michael A.

2017-01-01

Postmitotic differentiated neurons are among the most difficult cells to reprogram into induced pluripotent stem cells (iPSCs) because they have poor viability when cultured as dissociated cells. Other protocols to reprogram postmitotic neurons have required the inactivation of the p53 tumor suppressor. We describe a method that does not require p53 inactivation and induces reprogramming in cells purified from the retinae of reprogrammable mice in aggregates with wild-type retinal cells. After the first 10 days of reprogramming, the aggregates are then dispersed and plated on irradiated feeder cells to propagate and isolate individual iPSC clones. The reprogramming efficiency of different neuronal populations at any stage of development can be quantitated using this protocol. Reprogramming retinal neurons with this protocol will take 56 days, and these retina-derived iPSCs can undergo retinal differentiation to produce retinae in 34 days. In addition, we describe a quantitative assessment of retinal differentiation from these neuron-derived iPSCs called STEM-RET. The procedure quantitates eye field specification, optic cup formation, and retinal differentiation in 3-dimensional cultures using molecular, cellular and morphological criteria. An advanced level of cell culture experience is required to carry out this protocol. PMID:27658012

Chromatin remodelling: the industrial revolution of DNA around histones.

PubMed

Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

2006-06-01

Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

Doppler optical coherence tomography of retinal circulation.

PubMed

Tan, Ou; Wang, Yimin; Konduru, Ranjith K; Zhang, Xinbo; Sadda, SriniVas R; Huang, David

2012-09-18

Noncontact retinal blood flow measurements are performed with a Fourier domain optical coherence tomography (OCT) system using a circumpapillary double circular scan (CDCS) that scans around the optic nerve head at 3.40 mm and 3.75 mm diameters. The double concentric circles are performed 6 times consecutively over 2 sec. The CDCS scan is saved with Doppler shift information from which flow can be calculated. The standard clinical protocol calls for 3 CDCS scans made with the OCT beam passing through the superonasal edge of the pupil and 3 CDCS scan through the inferonal pupil. This double-angle protocol ensures that acceptable Doppler angle is obtained on each retinal branch vessel in at least 1 scan. The CDCS scan data, a 3-dimensional volumetric OCT scan of the optic disc scan, and a color photograph of the optic disc are used together to obtain retinal blood flow measurement on an eye. We have developed a blood flow measurement software called "Doppler optical coherence tomography of retinal circulation" (DOCTORC). This semi-automated software is used to measure total retinal blood flow, vessel cross section area, and average blood velocity. The flow of each vessel is calculated from the Doppler shift in the vessel cross-sectional area and the Doppler angle between the vessel and the OCT beam. Total retinal blood flow measurement is summed from the veins around the optic disc. The results obtained at our Doppler OCT reading center showed good reproducibility between graders and methods (<10%). Total retinal blood flow could be useful in the management of glaucoma, other retinal diseases, and retinal diseases. In glaucoma patients, OCT retinal blood flow measurement was highly correlated with visual field loss (R(2)>0.57 with visual field pattern deviation). Doppler OCT is a new method to perform rapid, noncontact, and repeatable measurement of total retinal blood flow using widely available Fourier-domain OCT instrumentation. This new technology may improve the

Automated detection of retinal disease.

PubMed

Helmchen, Lorens A; Lehmann, Harold P; Abràmoff, Michael D

2014-11-01

Nearly 4 in 10 Americans with diabetes currently fail to undergo recommended annual retinal exams, resulting in tens of thousands of cases of blindness that could have been prevented. Advances in automated retinal disease detection could greatly reduce the burden of labor-intensive dilated retinal examinations by ophthalmologists and optometrists and deliver diagnostic services at lower cost. As the current availability of ophthalmologists and optometrists is inadequate to screen all patients at risk every year, automated screening systems deployed in primary care settings and even in patients' homes could fill the current gap in supply. Expanding screens to all patients at risk by switching to automated detection systems would in turn yield significantly higher rates of detecting and treating diabetic retinopathy per dilated retinal examination. Fewer diabetic patients would develop complications such as blindness, while ophthalmologists could focus on more complex cases.

Current perspectives of herpesviral retinitis and choroiditis.

PubMed

Madhavan, H N; Priya, K; Biswas, J

2004-10-01

Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens.

Telemedicine diagnosis of cytomegalovirus retinitis by nonophthalmologists.

PubMed

Yen, Michael; Ausayakhun, Somsanguan; Chen, Jenny; Ausayakhun, Sakarin; Jirawison, Choeng; Heiden, David; Holland, Gary N; Margolis, Todd P; Keenan, Jeremy D

2014-09-01

Cytomegalovirus (CMV) retinitis continues to be a leading cause of blindness in many developing countries. Telemedicine holds the potential to increase the number of people screened for CMV retinitis, but it is unclear whether nonophthalmologists could be responsible for interpreting fundus photographs captured in a telemedicine program. To determine the accuracy of nonophthalmologist photographic graders in diagnosing CMV retinitis from digital fundus photographs. Fifteen nonexpert graders each evaluated 182 mosaic retinal images taken from the eyes of patients with AIDS who were evaluated at the Ocular Infectious Diseases Clinic at Chiang Mai University in Chiang Mai, Thailand. Graders diagnosed each image as CMV retinitis present, CMV retinitis absent, or unknown. The results from each grader were compared with those of an indirect ophthalmoscopic examination from an experienced on-site ophthalmologist as well as with the consensus grade given by a panel of CMV retinitis experts. Relative to the on-site ophthalmologist, the sensitivity of remote CMV retinitis diagnosis by nonexpert graders ranged from 64.0% to 95.5% (mean, 84.1%; 95% CI, 78.6%-89.6%)), and the specificity ranged from 65.6% to 92.5% (mean, 82.3%; 95% CI, 76.6%-88.0%)). Agreement between nonexpert and expert graders was high: the mean sensitivity and specificity values of nonexpert diagnosis using expert consensus as the reference standard were 93.2% (95% CI, 90.6%-95.8%) and 88.4% (95% CI, 85.4%-91.1%), respectively. Mean intrarater reliability also was high (mean Cohen κ, 0.83; 95% CI, 0.78-0.87). The sensitivity and specificity of remote diagnosis of CMV retinitis by nonexpert graders was variable, although several nonexperts achieved a level of accuracy comparable to that of CMV retinitis experts. More intensive training and periodic evaluations would be required if nonexperts are to be used in clinical practice.

Paediatric retinal detachment: aetiology, characteristics and outcomes.

PubMed

McElnea, Elizabeth; Stephenson, Kirk; Gilmore, Sarah; O'Keefe, Michael; Keegan, David

2018-01-01

To provide contemporary data on the aetiology, clinical features and outcomes of paediatric retinal detachment. A retrospective review of all those under 16y who underwent surgical repair for retinal detachment at a single centre between the years 2008 and 2015 inclusive was performed. In each case the cause of retinal detachment, the type of detachment, the presence or absence of macular involvement, the number and form of reparative surgeries undertaken, and the surgical outcome achieved was recorded. Twenty-eight eyes of 24 patients, 15 (62.5%) of whom were male and 9 (37.5%) of whom were female, their mean age being 11.6y and range 2-16y developed retinal detachment over the eight year period studied. Trauma featured in the development of retinal detachment in 14 (50.0%) cases. Retinal detachment was associated with other ocular and/or systemic conditions in 11 (39.3%) cases. A mean of 3.0 procedures with a range of 1-9 procedures per patient were undertaken in the management of retinal detachment. Complex vitrectomy combined with scleral buckling or complex vitrectomy alone were those most frequently performed. Mean postoperative visual acuity was 1.2 logMAR with range 0.0-3.0 logMAR. In 22 of 26 (84.6%) cases which underwent surgical repair the retina was attached at last follow-up. Aggressive management of paediatric retinal detachment including re-operation increases the likelihood of anatomical success. In cases where the retinal detachment can be repaired by an external approach alone there is a more favourable visual outcome.

Retrobulbar optic neuritis and rhegmatogenous retinal detachment in a fourteen-year-old girl with retinitis pigmentosa sine pigmento.

PubMed

Hatta, M; Hayasaka, S; Kato, T; Kadoi, C

2000-01-01

A 14-year-old girl complained of a sudden decrease in right visual acuity. The patient had night blindness, a mottled retina but no pigments, extinguished scotopic electroretinographic response, central scotoma in the right eye and rhegmatogenous retinal detachment. She had initially received laser photocoagulation around the retinal tear and then corticosteroid therapy, cryoretinopexy and segmental buckling. Her right visual acuity increased to 1.0. The association of retinitis pigmentosa sine pigmento, retrobulbar optic neuritis and rhegmatogenous retinal detachment, as demonstrated in our patient, may be uncommon. Copyright 2000 S. Karger AG, Basel

Imaging of retinal and choroidal vascular tumours

PubMed Central

Heimann, H; Jmor, F; Damato, B

2013-01-01

The most common intraocular vascular tumours are choroidal haemangiomas, vasoproliferative tumours, and retinal haemangioblastomas. Rarer conditions include cavernous retinal angioma and arteriovenous malformations. Options for ablating the tumour include photodynamic therapy, argon laser photocoagulation, trans-scleral diathermy, cryotherapy, anti-angiogenic agents, plaque radiotherapy, and proton beam radiotherapy. Secondary effects are common and include retinal exudates, macular oedema, epiretinal membranes, retinal fibrosis, as well as serous and tractional retinal detachment, which are treated using standard methods (ie, intravitreal anti-angiogenic agents or steroids as well as vitreoretinal procedures, such as epiretinal membrane peeling and release of retinal traction). The detection, diagnosis, and monitoring of vascular tumours and their complications have improved considerably thanks to advances in imaging. These include spectral domain and enhanced depth imaging optical coherence tomography (SD-OCT and EDI-OCT, respectively), wide-angle photography and angiography as well as wide-angle fundus autofluorescence. Such novel imaging has provided new diagnostic clues and has profoundly influenced therapeutic strategies so that vascular tumours and secondary effects are now treated concurrently instead of sequentially, enhancing any opportunities for conserving vision and the eye. In this review, we describe how SD-OCT, EDI-OCT, autofluorescence, wide-angle photography and wide-angle angiography have facilitated the evaluation of eyes with the more common vascular tumours, that is, choroidal haemangioma, retinal vasoproliferative tumours, and retinal haemangioblastoma. PMID:23196648

Clinical applications of fundus autofluorescence in retinal disease.

PubMed

Yung, Madeline; Klufas, Michael A; Sarraf, David

2016-01-01

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device, are available to the clinician. Each offers unique advantages for evaluating various retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating age related macular degeneration, macular dystrophies, retinitis pigmentosa, white dot syndromes, retinal drug toxicities, and various other retinal disorders. FAF may detect abnormalities beyond those detected on funduscopic exam, fluorescein angiography, or optical coherence tomography, and can be used to elucidate disease pathogenesis, form genotype-phenotype correlations, diagnose and monitor disease, and evaluate novel therapies. Given its ease of use, non-invasive nature, and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes common ocular fluorophores, imaging modalities, and FAF findings for a wide spectrum of retinal disorders.

Suppression of HSP27 Restores Retinal Function and Protects Photoreceptors From Apoptosis in a Light-Induced Retinal Degeneration Animal Model.

PubMed

Chien, Chih-Cheng; Huang, Chi-Jung; Tien, Lu-Tai; Cheng, Yu-Che; Ke, Chia-Ying; Lee, Yih-Jing

2017-06-01

We used a light-induced retinal degeneration animal model to investigate possible roles of heat shock protein 27 (HSP27) in retinal/photoreceptor protection. Sprague-Dawley rats were used for the light-induced retinal degeneration animal model. The histology of eye sections was observed for morphologic changes in the retina. Cell apoptosis was examined in each group using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and electroretinography was used to evaluate retinal function. Protein and mRNA expression levels of different retinal cell markers were also detected through immunofluorescence staining, Western blotting, and real-time PCR. The thickness of the outer nuclear layer significantly decreased after 7-day light exposure. Moreover, we injected a viral vector for silencing HSP27 expression into the eyes and observed that photoreceptors were better preserved in the HSP27-suppressed (sHSP27) retina 2 weeks after injection. HSP27 suppression also reduced retinal cell apoptosis caused by light exposure. In addition, the loss of retinal function caused by light exposure was reversed on suppressing HSP27 expression. We subsequently found that the expression of the Rho gene and immunofluorescence staining of rhodopsin and arrestin (cell markers for photoreceptors) increased in sHSP27-treated retinas. HSP27 suppression did not affect the survival of ganglion and amacrine cells. Retinal cell apoptosis and functional loss were observed after 7-day light exposure. However, in the following 2 weeks after light exposure, HSP27 suppression may initiate a protective effect for retinal cells, particularly photoreceptors, from light-induced retinal degeneration.

[Retinal whitening following vitrectomy for epiretinal macular membrane].

PubMed

Uemura, A

1993-09-01

To investigate the clinical pictures of retinal whitening following epiretinal membrane dissection. I studied retrospectively the records of 18 eyes which had undergone vitrectomy. Two types of retinal whitening were observed: cotton wool-like spots within the superficial retinal layers and a linear or dendritic pattern within the deep retinal layers. The spots were mainly noted in idiopathic cases and resolved completely in a few weeks, and the pattern was observed in macular pucker cases after retinal detachment surgery and persisted for a long time after vitrectomy.

Syphilitic punctate inner retinitis in immunocompetent gay men.

PubMed

Wickremasinghe, Sanjeewa; Ling, Cecilia; Stawell, Richard; Yeoh, Jonathan; Hall, Anthony; Zamir, Ehud

2009-06-01

To describe the features of an unusual syphilitic uveitis syndrome in a cluster of homosexual patients. Retrospective case series. Five consecutive patients diagnosed with syphilitic retinitis in our Melbourne uveitis clinic over a period of 8 months. The case notes of patients diagnosed with syphilitic retinitis were reviewed and the clinical features are presented and discussed. Description of retinal findings and documentation of any associated sequelae. All patients were homosexual men. Two were human immunodeficiency virus positive. None of the patients had been previously diagnosed with syphilis, although 3 presented with systemic symptoms and signs of secondary syphilis. All patients had marked anterior uveitis and vitritis. All patients had acute retinal arteriolitis and inner retinitis, with distinctive, inner retinal and preretinal white dots. These retinal findings were remarkably similar in all patients, and resolved with little or no sequelae after standard systemic treatment for syphilis, combined with oral prednisolone. Syphilitic retinitis may be an increasingly common clinical problem, reflecting the growing incidence of syphilis among homosexual men in Australia. Our patients showed stereotypical ocular and systemic features, which are useful in differentiating this condition clinically from other types of acute posterior uveitis, such as necrotizing viral retinitis. Proprietary or commercial disclosure may be found after the references.

[Viral retinitis following intravitreal triamcinolone injection].

PubMed

Zghal, I; Malek, I; Amel, C; Soumaya, O; Bouguila, H; Nacef, L

2013-09-01

Necrotizing viral retinitis is associated with infection by the Herpes family of viruses, especially herpes simplex virus (HSV), varicella zoster virus (VZV) and occasionally cytomegalovirus (CMV). When the diagnosis is suspected clinically, antiviral therapy must be instituted immediately. We report the case of a patient presenting with necrotizing viral retinitis 3 months following intravitreal injection of triamcinolone acetonide for diabetic macular edema. Fluorescein angiography demonstrated a superior temporal occlusive vasculitis. A diagnostic anterior chamber paracentesis was performed to obtain deoxyribo-nucleic acid (DNA) for a polymerase chain reaction (PCR) test for viral retinitis. PCR was positive for CMV. The patient was placed on intravenous ganciclovir. CMV retinitis is exceedingly rare in immunocompetent patients; however, it remains the most common cause of posterior uveitis in immunocompromised patients. The incidence of this entity remains unknown. Local immunosuppression, the dose and the frequency of injections may explain the occurrence of this severe retinitis. Copyright © 2013. Published by Elsevier Masson SAS.

[Indications for Retinal Laser Therapy Revisited].

PubMed

Enders, P; Schaub, F; Fauser, S

2017-02-10

Background Laser therapy is an important treatment option in retinal diseases, especially in cases of vascular involvement. Most approaches are based on coagulation of retinal structures. As there is increasing use of agents targetting vascular endothelial growth factor in the treatment of macular diseases, indications for the use of laser treatment need to be reviewed carefully, especially with respect to their significance in first line therapy. This article explains recent strategies and treatment protocols. Materials and Methods Review of current literature in PubMed as well as synopsis of relevant guidelines. Results and Conclusion Retinal laser therapy is still widely used within retinal opthalmology and covers a large spectrum of indications. Despite the success of medical approaches, retinal laser therapy remains an indispensable treatment option for proliferative diabetic retinopathy, central or peripheral vein occlusion and less frequent pathologies, such as retinopathy of prematurity or Coats's disease. Georg Thieme Verlag KG Stuttgart · New York.

Optical coherence tomography-guided retinal prosthesis design: model of degenerated retinal curvature and thickness for patient-specific devices.

PubMed

Opie, Nicholas L; Ayton, Lauren N; Apollo, Nicholas V; Ganesan, Kumaravelu; Guymer, Robyn H; Luu, Chi D

2014-06-01

Retinitis pigmentosa affects over 1.5 million people worldwide and is a leading cause of vision loss and blindness. While retinal prostheses have shown some success in restoring basic levels of vision, only generic, "one-size-fits-all" devices are currently being implanted. In this study, we used optical coherence tomography scans of the degenerated retina from 88 patients with retinitis pigmentosa to generate models of retinal thickness and curvature for the design of customized implants. We found the average retinal thickness at the fovea to be 152.9 ± 61.3 μm, increasing to a maximum retinal thickness of 250.9 ± 57.5 μm at a nasal eccentricity of 5°. These measures could be used to assist the development of custom-made penetrating electrodes to enhance and optimize epiretinal prostheses. From the retinal thickness measurements, we determined that the optimal length of penetrating electrodes to selectively stimulate retinal ganglion cell bodies and interneuron axons in the ganglion cell layer should be 30-100 μm, and to preferentially stimulate interneurons in the inner nuclear layer, electrodes should be 100-200 μm long. Electrodes greater than 200 μm long had the potential to penetrate through the retina into the choroid, which could cause devastating complications to the eye and should be avoided. The two- and three-dimensional models of retinal thickness developed in this study can be used to design patient-specific epiretinal implants that will help with safety and to optimize the efficacy of neuronal stimulation, ensuring the best functional performance of the device for patients. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Effect of cadmium chloride on the distal retinal pigment cells of the fiddler crab, Uca pugilator

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

Reddy, P.S.; Fingerman, M.; Nguyen, L.K.

1997-03-01

Crustaceans have two sets of pigmentary effectors, chromatophores and retinal pigment cells. Retinal pigments control the amount of light striking the rhabdom, the photosensitive portion of each ommatidium, screening the rhabdom in bright light and uncovering it in darkness or dim light. Migration of the distal pigment in the fiddler crab, Uca pugilalor, is regulated by a light-adapting hormone and a dark-adapting hormone. The black chromatophores of this crab are also controlled by a pair of hormones. Both pigmentary effectors exhibit circadian rhythms. The effects of some organic and inorganic pollutants on the ability of Uca pugilator to change colormore » have been described. Exposure of this crab to naphthalene or cadmium results in decreased ability to disperse the pigment in their black chromatophores, the exposed crabs becoming paler than the unexposed crabs. Norepinephrine triggers release of both the black pigment-dispersing hormone and the light-adapting hormone. In view of the facts that (a) these hormones which regulate the black chromatophores and distal pigment are synthesized in and released from the eyestalk neuroendocrine complex, (b) the black pigment-dispersing hormone and the light-adapting hormone may actually be the same hormone. having two different activities and (c) release of both the black pigment-dispersing hormone and the light-adapting hormone is triggered by norepinephrine, the present investigation was carried out to determine the effect of cadmium on distal pigment migration in Uca pugilator. More specifically, for comparison with the previously reported effect of cadmium on pigment migration in the black chromatophores, we wished to determine whether the distal pigment of fiddler crabs exposed to cadmium chloride is capable of as wide a range of movement as in unexposed crabs, and if not what might be the explanation. This is the first report of the effect of a pollutant on a retinal pigment of any crustacean. 12 refs., 3 tabs.« less

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN MACULA-INVOLVING CYTOMEGALOVIRUS RETINITIS.

PubMed

Gupta, Mrinali P; Patel, Sarju; Orlin, Anton; Marlow, Elizabeth; Chee, Ru-Ik; Nadelmann, Jennifer; Chan, R V Paul; DʼAmico, Donald J; Kiss, Szilard

2018-05-01

To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis. Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole-associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis. Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.

Retinitis pigmentosa.

PubMed

Hamel, Christian

2006-10-11

Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis).

Retinitis pigmentosa

PubMed Central

Hamel, Christian

2006-01-01

Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis). PMID:17032466

Visual Acuity is Related to Parafoveal Retinal Thickness in Patients with Retinitis Pigmentosa and Macular Cysts

PubMed Central

Brockhurst, Robert J.; Gaudio, Alexander R.; Berson, Eliot L.

2008-01-01

Purpose To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa. Methods In 316 patients with typical forms of retinitis pigmentosa, we measured visual acuities with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, detected macular cysts with optical coherence tomography (OCT), and quantified retinal thicknesses by OCT. We used the FREQ, LOGISTIC, and GENMOD procedures of SAS to evaluate possible risk factors for cyst prevalence and the MIXED procedure to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula. Results We found macular cysts in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (p = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (p = 0.038) and within a ring spanning an eccentricity of 5° to 10° from the foveal center (p = 0.004). Conclusions Macular cysts are a common occurrence in retinitis pigmentosa, especially among patients with dominantly-inherited disease. Visual acuity is influenced by edema in the parafovea, as well as in the fovea. PMID:18552390

Retinal oximetry during treatment of retinal vein occlusion by ranibizumab in patients with high blood pressure and dyslipidemia.

PubMed

Keilani, C; Halalchi, A; Wakpi Djeugue, D; Regis, A; Abada, S

2016-12-01

In the present study, we examined retinal vascular oxygen saturation in patients with retinal vein occlusion (RVO), high blood pressure (HBP) and dyslipidemia, before and during intravitreal vascular endothelial growth factor (VEGF) injection (ranibizumab). We retrospectively reviewed the medical records of six patients with visual acuity (VA) reduced by macular edema (ME) secondary to RVO with HBP and dyslipidemia, who underwent intravitreal anti-VEGF injection between October 2014 and February 2015 in the department of ophthalmology of François-Quesnay Hospital at Mantes-la-Jolie (France). The main inclusion criterion was the presence of RVO with ME and decreased VA. The primary endpoint was improvement of retinal venous oxygen saturation in patients with RVO before and 3 months after intravitreal ranibizumab injection. Secondary outcomes were improvement of retinal arterial oxygen saturation, improvement of best-corrected visual acuity (BCVA) on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, regression of ME measured by the central macular thickness (CMT) in nm and studying the correlation between blood pressure (BP) and retinal venous oxygen saturation before and after ranibizumab. Six eyes of six patients were included. Before treatment, the mean (standard deviation [SD]) of the retinal venous saturation (%) was 38.1±14.2. Three months after the injections, the mean (SD) of the retinal venous saturation (%) increased statistically significantly 49.2±11 (P=0.03). In this study, retinal venous oxygen saturation in patients with RVO, HBP and dyslipidemia was partially normalized during intravitreal ranibizumab treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

New Wrinkles in Retinal Densitometry

PubMed Central

Masella, Benjamin D.; Hunter, Jennifer J.; Williams, David R.

2014-01-01

Purpose. Retinal densitometry provides objective information about retinal function. But, a number of factors, including retinal reflectance changes that are not directly related to photopigment depletion, complicate its interpretation. We explore these factors and suggest a method to minimize their impact. Methods. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to measure changes in photoreceptor reflectance in monkeys before and after photopigment bleaching with 514-nm light. Reflectance measurements at 514 nm and 794 nm were recorded simultaneously. Several methods of normalization to extract the apparent optical density of the photopigment were compared. Results. We identified stimulus-related fluctuations in 794-nm reflectance that are not associated with photopigment absorptance and occur in both rods and cones. These changes had a magnitude approaching those associated directly with pigment depletion, precluding the use of infrared reflectance for normalization. We used a spatial normalization method instead, which avoided the fluctuations in the near infrared, as well as a confocal AOSLO designed to minimize light from layers other than the receptors. However, these methods produced a surprisingly low estimate of the apparent rhodopsin density (animal 1: 0.073 ± 0.006, animal 2: 0.032 ± 0.003). Conclusions. These results confirm earlier observations that changes in photopigment absorption are not the only source of retinal reflectance change during dark adaptation. It appears that the stray light that has historically reduced the apparent density of cone photopigment in retinal densitometry arises predominantly from layers near the photoreceptors themselves. Despite these complications, this method provides a valuable, objective measure of retinal function. PMID:25316726

Retinal imaging using adaptive optics technology☆

PubMed Central

Kozak, Igor

2014-01-01

Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effect of wave front distortions. Retinal imaging using AO aims to compensate for higher order aberrations originating from the cornea and the lens by using deformable mirror. The main application of AO retinal imaging has been to assess photoreceptor cell density, spacing, and mosaic regularity in normal and diseased eyes. Apart from photoreceptors, the retinal pigment epithelium, retinal nerve fiber layer, retinal vessel wall and lamina cribrosa can also be visualized with AO technology. Recent interest in AO technology in eye research has resulted in growing number of reports and publications utilizing this technology in both animals and humans. With the availability of first commercially available instruments we are making transformation of AO technology from a research tool to diagnostic instrument. The current challenges include imaging eyes with less than perfect optical media, formation of normative databases for acquired images such as cone mosaics, and the cost of the technology. The opportunities for AO will include more detailed diagnosis with description of some new findings in retinal diseases and glaucoma as well as expansion of AO into clinical trials which has already started. PMID:24843304

Highly efficient retinal metabolism in cones

PubMed Central

Miyazono, Sadaharu; Shimauchi-Matsukawa, Yoshie; Tachibanaki, Shuji; Kawamura, Satoru

2008-01-01

After bleaching of visual pigment in vertebrate photoreceptors, all-trans retinal is reduced to all-trans retinol by retinol dehydrogenases (RDHs). We investigated this reaction in purified carp rods and cones, and we found that the reducing activity toward all-trans retinal in the outer segment (OS) of cones is >30 times higher than that of rods. The high activity of RDHs was attributed to high content of RDH8 in cones. In the inner segment (IS) in both rods and cones, RDH8L2 and RDH13 were found to be the major enzymes among RDH family proteins. We further found a previously undescribed and effective pathway to convert 11-cis retinol to 11-cis retinal in cones: this oxidative conversion did not require NADP+ and instead was coupled with reduction of all-trans retinal to all-trans retinol. The activity was >50 times effective than the oxidizing activity of RDHs that require NADP+. These highly effective reactions of removal of all-trans retinal by RDH8 and production of 11-cis retinal by the coupling reaction are probably the underlying mechanisms that ensure effective visual pigment regeneration in cones that function under much brighter light conditions than rods. PMID:18836074

Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells

PubMed Central

2010-01-01

Background Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. Here, we investigated the genomic events occurring during this process induced by functional blockade of α5β1 integrin in liver progenitor cells. Results Cells treated with a specific antibody against α5β1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus. Conclusion Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape. PMID:20958983

Ocular toxoplasmosis and retinal detachment: five case reports.

PubMed

Kianersi, F; Naderi Beni, A; Ghanbari, H; Fazel, F

2012-10-01

Ocular toxoplasmosis is a potentially blinding cause of posterior uveitis. Retinal detachment is rare complication of ocular toxoplasmosis. To report the clinical course and prognosis of retinal breaks and detachments occurring in patients with ocular toxoplasmosis. This study was a retrospective, non-comparative case series of five patients with ocular toxoplasmosis who had consulted us with retinal detachment. All of the participants had retinal detachment after severe and treatment resistant toxoplasmic retinochoroiditis, leaving one of them with decreased visual acuity to light perception in spite of treatment and final visual acuity was 20/100 or better in four patients. The functional prognosis for the patients with retinal detachment was poor. Careful retinal examination in ocular toxoplasmosis is warranted, especially in patients with severe intraocular inflammation.

PTP-PEST controls EphA3 activation and ephrin-induced cytoskeletal remodelling.

PubMed

Mansour, Mariam; Nievergall, Eva; Gegenbauer, Kristina; Llerena, Carmen; Atapattu, Lakmali; Hallé, Maxime; Tremblay, Michel L; Janes, Peter W; Lackmann, Martin

2016-01-15

Eph receptors and their corresponding membrane-bound ephrin ligands regulate cell positioning and establish tissue patterns during embryonic and oncogenic development. Emerging evidence suggests that assembly of polymeric Eph signalling clusters relies on cytoskeletal reorganisation and underlies regulation by protein tyrosine phosphatases (PTPs). PTP-PEST (also known as PTPN12) is a central regulator of actin cytoskeletal dynamics. Here, we demonstrate that an N-terminal fragment of PTP-PEST, generated through an ephrinA5-triggered and spatially confined cleavage mediated by caspase-3, attenuates EphA3 receptor activation and its internalisation. Isolation of EphA3 receptor signalling clusters within intact plasma membrane fragments obtained by detergent-free cell fractionation reveals that stimulation of cells with ephrin triggers effective recruitment of this catalytically active truncated form of PTP-PEST together with key cytoskeletal and focal adhesion proteins. Importantly, modulation of actin polymerisation using pharmacological and dominant-negative approaches affects EphA3 phosphorylation in a similar manner to overexpression of PTP-PEST. We conclude that PTP-PEST regulates EphA3 activation both by affecting cytoskeletal remodelling and through its direct action as a PTP controlling EphA3 phosphorylation, indicating its multifaceted regulation of Eph signalling. © 2016. Published by The Company of Biologists Ltd.

The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

PubMed

Walley, Justin W; Rowe, Heather C; Xiao, Yanmei; Chehab, E Wassim; Kliebenstein, Daniel J; Wagner, Doris; Dehesh, Katayoon

2008-12-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

A selected review of current retinal research and study.

PubMed

Cohen, J

1979-02-01

This paper presents a digest of 50 retinal research projects reported in one British and two American journals from July 1976 through June 1977. The articles reviewed report recent developments pertaining to effects of excessive light on retinal tissue in newborn rats, pathogenesis of cotton-wool spots, control of the blood-retinal barrier in diabetes, infections, macular diseases, variations in retinal pigment epithelium, and retinal detachment.

Retinal detachment in pseudophakia.

PubMed

Galin, M A; Poole, T A; Obstbaum, S A

1979-07-01

In a series of cataract patients excluding myopic individuals, under age 60 years, and cases in which vitreous loss occurred, retinal detachment was no less frequent after intracapsular cataract extraction and Sputnik iris supported lenses than in controls. Both groups were followed up for a minimum of two years. The detachments predominantly occurred from retinal breaks in areas of the retina that looked normal preoperatively.

Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling.

PubMed

Kistemaker, Loes E M; Gosens, Reinoud

2015-03-01

Acetylcholine is the primary parasympathetic neurotransmitter in the airways, where it not only induces bronchoconstriction and mucus secretion, but also regulates airway inflammation and remodeling. In this review, we propose that these effects are all primarily mediated via the muscarinic M3 receptor. Acetylcholine promotes inflammation and remodeling via direct effects on airway cells, and via mechanical stress applied to the airways sequential to bronchoconstriction. The effects on inflammation and remodeling are regulated by both neuronal and non-neuronal acetylcholine. Taken together, we believe that the combined effects of anticholinergic therapy on M3-mediated bronchoconstriction, mucus secretion, inflammation, and remodeling may account for the positive outcome of treatment with these drugs for patients with chronic pulmonary obstructive disease (COPD) or asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toward high-resolution optoelectronic retinal prosthesis

NASA Astrophysics Data System (ADS)

Palanker, Daniel; Huie, Philip; Vankov, Alexander; Asher, Alon; Baccus, Steven

2005-04-01

It has been already demonstrated that electrical stimulation of retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. Current retinal implants provide very low resolution (just a few electrodes), while several thousand pixels are required for functional restoration of sight. We present a design of the optoelectronic retinal prosthetic system that can activate a retinal stimulating array with pixel density up to 2,500 pix/mm2 (geometrically corresponding to a visual acuity of 20/80), and allows for natural eye scanning rather than scanning with a head-mounted camera. The system operates similarly to "virtual reality" imaging devices used in military and medical applications. An image from a video camera is projected by a goggle-mounted infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. Such a system provides a broad field of vision by allowing for natural eye scanning. The goggles are transparent to visible light, thus allowing for simultaneous utilization of remaining natural vision along with prosthetic stimulation. Optical control of the implant allows for simple adjustment of image processing algorithms and for learning. A major prerequisite for high resolution stimulation is the proximity of neural cells to the stimulation sites. This can be achieved with sub-retinal implants constructed in a manner that directs migration of retinal cells to target areas. Two basic implant geometries are described: perforated membranes and protruding electrode arrays. Possibility of the tactile neural stimulation is also examined.

Recovery from retinal lesions: molecular plasticity mechanisms in visual cortex far beyond the deprived zone.

PubMed

Hu, Tjing-Tjing; Van den Bergh, Gert; Thorrez, Lieven; Heylen, Kevin; Eysel, Ulf T; Arckens, Lutgarde

2011-12-01

In cats with central retinal lesions, deprivation of the lesion projection zone (LPZ) in primary visual cortex (area 17) induces remapping of the cortical topography. Recovery of visually driven cortical activity in the LPZ involves distinct changes in protein expression. Recent observations, about molecular activity changes throughout area 17, challenge the view that its remote nondeprived parts would not be involved in this recovery process. We here investigated the dynamics of the protein expression pattern of remote nondeprived area 17 triggered by central retinal lesions to explore to what extent far peripheral area 17 would contribute to the topographic map reorganization inside the visual cortex. Using functional proteomics, we identified 40 proteins specifically differentially expressed between far peripheral area 17 of control and experimental animals 14 days to 8 months postlesion. Our results demonstrate that far peripheral area 17 is implicated in the functional adaptation to the visual deprivation, involving a meshwork of interacting proteins, operating in diverse pathways. In particular, endocytosis/exocytosis processes appeared to be essential via their intimate correlation with long-term potentiation and neurite outgrowth mechanisms.

Inherited Retinal Degenerative Disease Clinical Trial Network. Addendum

DTIC Science & Technology

2010-10-01

by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at approximately 200,000 individuals. RP... Retinitis Pigmentosa ). NNRI is awaiting final protocol review and HRPO approval for NNRI and the three enrolling clinical sites- the CTEC site at...acid) in individuals with autosomal dominant retinitis pigmentosa , with the ability to expand the enrollment to individuals with autosomal recessive

Retinitis pigmentosa and congenital toxoplasmosis: a rare coexistence.

PubMed

Chhabra, Manpreet S; Prakash, Gunjan; Vashisht, Nagender; Garg, S P

2007-01-01

We describe a previously unreported co-existence of retinitis pigmentosa and congenital toxoplasmosis. An eight year old male presented to our center with complaints of decreased night vision. Fundus evaluations in both the eyes demonstrated features typical of retinitis pigmentosa. There were well-defined punched out healed chorio-retinal scars suggestive of congenital toxoplasmosis. On the basis of history, clinical findings and reduction of a and b wave amplitudes on scotopic and photopic electroretinograph, a diagnosis of retinitis pigmentosa with congenital toxoplasmosis was made. Retinitis pigmentosa may co-exist with congenital toxoplasmosis that may affect the patient's overall ocular morbidity and visual acuity.

An Analysis of the Residential Remodeling Occupation.

ERIC Educational Resources Information Center

Scruggs, Kenneth

The general purpose of the occupational analysis is to provide workable, basic information dealing with the many and varied duties performed in the residential remodeling occupation. The analysis only briefly covers the many areas of residential remodeling. The document opens with a brief introduction followed by a job description. The bulk of the…

Application of stem cell-derived retinal pigmented epithelium in retinal degenerative diseases: present and future.

PubMed

Luo, Mingyue; Chen, Youxin

2018-01-01

As a constituent of blood-retinal barrier and retinal outer segment (ROS) scavenger, retinal pigmented epithelium (RPE) is fundamental to normal function of retina. Malfunctioning of RPE contributes to the onset and advance of retinal degenerative diseases. Up to date, RPE replacement therapy is the only possible method to completely reverse retinal degeneration. Transplantation of human RPE stem cell-derived RPE (hRPESC-RPE) has shown some good results in animal models. With promising results in terms of safety and visual improvement, human embryonic stem cell-derived RPE (hESC-RPE) can be expected in clinical settings in the near future. Despite twists and turns, induced pluripotent stem cell-derived RPE (iPSC-RPE) is now being intensely investigated to overcome genetic and epigenetic instability. By far, only one patient has received iPSC-RPE transplant, which is a hallmark of iPSC technology development. During follow-up, no major complications such as immunogenicity or tumorigenesis have been observed. Future trials should keep focusing on the safety of stem cell-derived RPE (SC-RPE) especially in long period, and better understanding of the nature of stem cell and the molecular events in the process to generate SC-RPE is necessary to the prosperity of SC-RPE clinical application.

Nestin expression in the retina of rats with inherited retinal degeneration.

PubMed

Valamanesh, Fatemeh; Monnin, Julie; Morand-Villeneuve, Nadège; Michel, Germaine; Zaher, Murhaf; Miloudi, Sofiane; Chemouni, Deborah; Jeanny, Jean-Claude; Versaux-Botteri, Claudine

2013-05-01

Nestin is found in radial glia and neuronal/glial progenitor cells during retinal development, and is re-expressed after acute damage in the retina of adult mammals. We have investigated nestin expression in the retina of the Royal College of Surgeons (RCS) rat model of human inherited blindness, Retinitis pigmentosa (RP). During the first postnatal week, nestin immunoreactivity was located in elongated processes resembling radial glia in both control and dystrophic animals. During the second postnatal week, the density of nestin immunoreactive radial processes decreased progressively starting in the outer retina. At postnatal day 20 (PNd20), Nestin immunoreactive radial processes were no longer visible, with immunoreactivity restricted to structures resembling Müller end-feet and/or astrocytes located in the ganglion cell layer (GCL) in both control and dystrophic rats. These morphological results were confirmed by Western blotting and qPCR analysis. The level of nestin remained low in control animals at different time points up to 1 year, but we observed a re-expression of this protein from PNd30 in the dystrophic animals. The morphology of cells re-expressing nestin resembled that of radial glia and/or Muller cells, but co-localization of nestin and glutamine synthetase (GS: a marker of mature Müller cells) was only partial. Interestingly, whereas Western blot analysis confirmed the increase in protein levels from PNd30 onwards, mRNA levels remained low in dystrophic rats. Additional studies demonstrated that the discrepancy between protein and mRNA contents could be due to a dysfunction in proteasome activity as often observed in neurodegenerative pathologies. In conclusion, because of its localization in astrocytes and in radial processes resembling radial glia in the pathologic adult retina, nestin may be involved in mechanisms such as cell migration, generation of new neurons or glial cells and/or in retinal (re)modeling in dystrophic adult animals. The

Reprogramming the metabolome rescues retinal degeneration.

PubMed

Park, Karen Sophia; Xu, Christine L; Cui, Xuan; Tsang, Stephen H

2018-05-01

Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal metabolic dysfunction as causes of degeneration. Recent publications have identified a number of metabolic processes-including but not limited to glucose and oxygen metabolism-that, when perturbed, play a role in the degeneration of photoreceptor cells. As a result, such studies have led to further research elucidating methods for prolonging photoreceptor survival in an effort to halt degeneration in its early stages. This review will explore the ways in which metabolomics has deepened our understanding of the causes of retinal degeneration and discuss how metabolomics can be used to prevent retinal degeneration from progressing to its later disease stages.

Dynamics of retinal photocoagulation and rupture

NASA Astrophysics Data System (ADS)

Sramek, Christopher; Paulus, Yannis; Nomoto, Hiroyuki; Huie, Phil; Brown, Jefferson; Palanker, Daniel

2009-05-01

In laser retinal photocoagulation, short (<20 ms) pulses have been found to reduce thermal damage to the inner retina, decrease treatment time, and minimize pain. However, the safe therapeutic window (defined as the ratio of power for producing a rupture to that of mild coagulation) decreases with shorter exposures. To quantify the extent of retinal heating and maximize the therapeutic window, a computational model of millisecond retinal photocoagulation and rupture was developed. Optical attenuation of 532-nm laser light in ocular tissues was measured, including retinal pigment epithelial (RPE) pigmentation and cell-size variability. Threshold powers for vaporization and RPE damage were measured with pulse durations ranging from 1 to 200 ms. A finite element model of retinal heating inferred that vaporization (rupture) takes place at 180-190°C. RPE damage was accurately described by the Arrhenius model with activation energy of 340 kJ/mol. Computed photocoagulation lesion width increased logarithmically with pulse duration, in agreement with histological findings. The model will allow for the optimization of beam parameters to increase the width of the therapeutic window for short exposures.

Assessment of Murine Retinal Function by Electroretinography

PubMed Central

Benchorin, Gillie; Calton, Melissa A.; Beaulieu, Marielle O.; Vollrath, Douglas

2017-01-01

The electroretinogram (ERG) is a sensitive and noninvasive method for testing retinal function. In this protocol, we describe a method for performing ERGs in mice. Contact lenses on the mouse cornea measure the electrical response to a light stimulus of photoreceptors and downstream retinal cells, and the collected data are analyzed to evaluate retinal function. PMID:29177186

The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

PubMed Central

Walley, Justin W.; Rowe, Heather C.; Xiao, Yanmei; Chehab, E. Wassim; Kliebenstein, Daniel J.; Wagner, Doris; Dehesh, Katayoon

2008-01-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks. PMID:19079584

Regulation of human retinal blood flow by endothelin-1.

PubMed

Polak, Kaija; Luksch, Alexandra; Frank, Barbara; Jandrasits, Kerstin; Polska, Elzbieta; Schmetterer, Leopold

2003-05-01

There is evidence from in vitro and animal studies that endothelin is a major regulator of retinal blood flow. We set out to characterize the role of the endothelin-system in the blood flow control of the human retina. Two studies in healthy subjects were performed. The study design was randomized, placebo-controlled, double-masked, balanced, two-way crossover in protocol A and three way-way crossover in protocol B. In protocol A 18 healthy male subjects received intravenous endothelin-1 (ET-1) in a dose of 2.5 ng kg (-1)min(-1) for 30 min or placebo on two different study days and retinal vessel diameters were measured. In protocol B 12 healthy male subjects received ET-1 in stepwise increasing doses of 0, 1.25, 2.5 and 5 ng kg (-1)min(-1) (each infusion step over 20 min) in co-infusion with the specific ET(A)-receptor antagonist BQ123 (60 microg min (-1)) or placebo or BQ123 alone investigating retinal vessel diameters, retinal blood velocity and retinal blood flow. Measurements of retinal vessel size were done with the Zeiss retinal vessel analyzer. Measurements of blood velocities were done with bi-directional laser Doppler velocimetry. From these measurements retinal blood flow was calculated. In protocol A exogenous ET-1 tended to decrease retinal arterial diameter, but this effect was not significant versus placebo. No effect on retinal venous diameter was seen. In protocol B retinal venous blood velocity and retinal blood flow was significantly reduced after administration of exogenous ET-1. These effects were significantly blunted when BQ-123 was co-administered. By contrast, BQ-123 alone had no effect on retinal hemodynamic parameters. Concluding, BQ123 antagonizes the effects of exogenously administered ET-1 on retinal blood flow in healthy subjects. In addition, the results of the present study are compatible with the hypothesis that ET-1 exerts its vasoconstrictor effects in the retina mainly on the microvessels.

[Gene therapy for inherited retinal dystrophies].

PubMed

Côco, Monique; Han, Sang Won; Sallum, Juliana Maria Ferraz

2009-01-01

The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these conditions and the patients can expect a progressive loss of vision. Accurate genetic counseling and support for rehabilitation are indicated. Research into the molecular and genetic basis of disease is continually expanding and improving the prospects for rational treatments. In this way, gene therapy, defined as the introduction of exogenous genetic material into human cells for therapeutic purposes, may ultimately offer the greatest treatment for the inherited retinal dystrophies. The eye is an attractive target for gene therapy because of its accessibility, immune privilege and translucent media. A number of retinal diseases affecting the eye have known gene defects. Besides, there is a well characterized animal model for many of these conditions. Proposals for clinical trials of gene therapy for inherited retinal degenerations owing to defects in the gene RPE65, have recently received ethical approval and the obtained preliminary results brought large prospects in the improvement on patient's quality of life.

Retinal phlebitis associated with autoimmune hemolytic anemia.

PubMed

Chew, Fiona L M; Tajunisah, Iqbal

2009-01-01

To describe a case of retinal phlebitis associated with autoimmune hemolytic anemia. Observational case report. A 44-year-old Indian man diagnosed with autoimmune hemolytic anemia presented with a 1-week history of blurred vision in both eyes. Fundus biomicroscopy revealed bilateral peripheral retinal venous sheathing and cellophane maculopathy. Fundus fluorescent angiogram showed bilateral late leakage from the peripheral venous arcades and submacular fluid accumulation. The retinal phlebitis resolved following a blood transfusion and administration of systemic steroids. Retinopathy associated with autoimmune hemolytic anemia is not well known. This is thought to be the first documentation of retinal phlebitis occurring in this condition.

RosettaRemodel: A Generalized Framework for Flexible Backbone Protein Design

PubMed Central

Huang, Po-Ssu; Ban, Yih-En Andrew; Richter, Florian; Andre, Ingemar; Vernon, Robert; Schief, William R.; Baker, David

2011-01-01

We describe RosettaRemodel, a generalized framework for flexible protein design that provides a versatile and convenient interface to the Rosetta modeling suite. RosettaRemodel employs a unified interface, called a blueprint, which allows detailed control over many aspects of flexible backbone protein design calculations. RosettaRemodel allows the construction and elaboration of customized protocols for a wide range of design problems ranging from loop insertion and deletion, disulfide engineering, domain assembly, loop remodeling, motif grafting, symmetrical units, to de novo structure modeling. PMID:21909381

Retinal astrocytoma in a dog.

PubMed

Kuroki, Keiichi; Kice, Nathan; Ota-Kuroki, Juri

2017-09-01

A miniature schnauzer dog presenting with hyphema and glaucoma of the right eye had a retinal neoplasm. Neoplastic cells stained positively for glial fibrillary acidic protein, vimentin, and S-100 and largely negatively for oligodendrocyte transcription factor 2 by immunohistochemistry. The clinical and histopathological features of canine retinal astrocytomas are discussed.

Perceptual Fading without Retinal Adaptation

ERIC Educational Resources Information Center

Hsieh, Po-Jang; Colas, Jaron T.

2012-01-01

A retinally stabilized object readily undergoes perceptual fading and disappears from consciousness. This startling phenomenon is commonly believed to arise from local bottom-up sensory adaptation to edge information that occurs early in the visual pathway, such as in the lateral geniculate nucleus of the thalamus or retinal ganglion cells. Here…

[To cognize retinitis pigmentosa with scientific view].

PubMed

Li, Gen-lin

2009-03-01

Retinitis pigmentosa (RP) is the most common inherited eye disease that usually leads into blind, and is high simplex and clinical heterogeneity. Recent years, some new hereditary forms have been found, such as digenic RP, mitochondrial RP, incomplete dominant inheritance RP. The phenotype of RP is multiplicity. Incompatible phenomenon between genotype and phenotypes was shown in some genes such as peripherin/RDS, RHO, RP2 and RP3. The complicated phenotype was shown in the rare RP forms, such as centricity RP, stemma RP, retinitis pigmentosa sine pigmento, and retinal degeneration slow. Retinal transplantation, retinal implantation, drug and neurotrophic factor therapy, and gene therapy have been well studied worldwide and presented some hopeful efficacy. Ophthalmologists and practitioners should cognize the new advance and new knowledge on RP therapy with a scientific view for better serving the RP patients.

Retinal detachment caused by Arruga suture scleral intrusion. Treatment.

PubMed

Sánchez-Vicente, J L; Rueda-Rueda, T; González-García, M L; López-Herrero, F; Sánchez-Vicente, P; Castilla-Lázpita, A

2015-10-01

We present the case of an 81-year-old man with retinal detachment caused by intrusion of an Arruga suture. The encircling buckle was located in the sub-retinal space and caused retinal breaks with retinal detachment A pars plana vitrectomy was performed along with intraocular cutting of the Arruga suture with retinal re-attachment. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Wavelength dependence of laser-induced retinal injury

NASA Astrophysics Data System (ADS)

Lund, David J.; Edsall, Peter; Stuck, Bruce E.

2005-04-01

The threshold for laser-induced retinal damage is dependent primarily upon the laser wavelength and the exposure duration. The study of the wavelength dependence of the retinal damage threshold has been greatly enhanced by the availability of tunable lasers. The Optical Parametric Oscillator (OPO), capable of providing useful pulse energy throughout a tuning range from 400 nm to 2200 nm, made it possible to determine the wavelength dependence of laser-induced retinal damage thresholds for q-switched pulses throughout the visible and NIR spectrum. Studies using the a tunable TI:Saph laser and several fixed-wavelength lasers yielded threshold values for 0.1 s exposures from 440 nm to 1060 nm. Laser-induced retinal damage for these exposure durations results from thermal conversion of the incident laser irradiation and an action spectrum for thermal retinal damage was developed based on the wavelength dependent transmission and absorption of ocular tissue and chromatic aberration of the eye optics. Long (1-1000s) duration exposures to visible laser demonstrated the existence of non-thermal laser-induced retinal damage mechanisms having a different action spectrum. This paper will present the available data for the wavelength dependence of laser-induced thermal retinal damage and compare this data to the maximum permissible exposure levels (MPEs) provided by the current guidelines for the safe use of lasers.

Multifocal retinitis in New Zealand sheep dogs.

PubMed

Hughes, P L; Dubielzig, R R; Kazacos, K R

1987-01-01

Thirty-nine percent of 1,448 working sheep dogs were affected with varying degrees of multifocal retinal disease on ophthalmoscopic examination. Lesions consisted of localized areas of hyperreflexia in the tapetal fundus, often associated with hyperpigmentation. Severely affected animals had widespread hyperreflexia with retinal vascular attenuation. Only 6% of 125 New Zealand dogs raised in urban environment were similarly affected. Both eyes of 70 dogs from New Zealand were examined histologically. Forty-seven of 70 dogs had ocular inflammatory disease. Ten other dogs had noninflammatory eye disease, and 13 dogs had normal eyes. Histologically, eyes with inflammatory disease were divided into three categories: Dogs 3 years of age or less with active inflammatory disease of the retina, uvea, and vitreous. Four dogs in this group had migrating nematode larvae identified morphologically as genus Toxocara. Diffuse retinitis and retinal atrophy in conjunction with localized retinal necrosis and choroidal fibrosis. Dogs in this category were severely, clinically affected. Chronic, low-grade retinitis with variable retinal atrophy. Most dogs in this category were over 3 years of age, and many were visually functional. The existence of a definable spectrum of morphological changes associated with inflammation, suggests that Toxocara sp. ocular larva migrans may be the cause of a highly prevalent, potentially blinding syndrome of working sheep dogs in New Zealand.

Retinitis pigmentosa, pigmentary retinopathies, and neurologic diseases.

PubMed

Bhatti, M Tariq

2006-09-01

Retinitis pigmentosa (RP) refers to a group of inherited retinal diseases with phenotypic and genetic heterogeneity. The pathophysiologic basis of the progressive visual loss in patients with RP is not completely understood but is felt to be due to a primary retinal photoreceptor cell degenerative process mainly affecting the rods of the peripheral retina. In most cases RP is seen in isolation (nonsyndromic), but in some other cases it may be a part of a genetic, metabolic, or neurologic syndrome or disorder. Nyctalopia, or night blindness, is the most common symptom of RP. The classic fundus appearance of RP includes retinal pigment epithelial cell changes resulting in retinal hypo- or hyperpigmentation ("salt-and-pepper"), retinal granularity, and bone spicule formation. The retinal vessels are often narrowed or attenuated and there is a waxy pallor appearance of the optic nerve head. Electroretinography will demonstrate rod and cone photoreceptor cell dysfunction and is a helpful test in the diagnosis and monitoring of patients with RP. A detailed history with pedigree analysis, a complete ocular examination, and the appropriate paraclinical testing should be performed in patients complaining of visual difficulties at night or in dim light. This review discusses the clinical manifestations of RP as well as describing the various systemic diseases, with a special emphasis on neurologic diseases, associated with a pigmentary retinopathy.

Astaxanthin Protects Against Retinal Damage: Evidence from In Vivo and In Vitro Retinal Ischemia and Reperfusion Models.

PubMed

Otsuka, Tomohiro; Shimazawa, Masamitsu; Inoue, Yuki; Nakano, Yusuke; Ojino, Kazuki; Izawa, Hiroshi; Tsuruma, Kazuhiro; Ishibashi, Takashi; Hara, Hideaki

2016-11-01

Astaxanthin exhibits various pharmacological activities, including anti-oxidative, anti-tumor, and anti-inflammatory effects, and is thought to exert a neuroprotective effect via these mechanisms. The purpose of this study was to investigate the protective effects of astaxanthin on neuronal cell death using a retinal ischemia/reperfusion model. In vivo, retinal ischemia was induced by 5 h unilateral ligation of the pterygopalatine artery (PPA) and the external carotid artery (ECA) in ddY mice. Astaxanthin (100 mg/kg) was administered orally 1 h before induction of ischemia, immediately after reperfusion, at 6 or 12 h after reperfusion, and twice daily for the following 4 days. Histological analysis and an electroretinogram (ERG) were performed 5 days after ischemia/reperfusion. In vitro, cell death was induced in the RGC-5 (retinal precursor cells) by oxygen-glucose deprivation (OGD), and the rates of cell death and production of intracellular reactive oxygen species (ROS) were measured using nuclear staining and a ROS reactive reagent, CM-H 2 DCFDA. Histological studies revealed that astaxanthin significantly reduced retinal ischemic damage and ERG reduction. In in vitro studies, astaxanthin inhibited cell death and ROS production in a concentration-dependent manner. Collectively, these results indicate that astaxanthin inhibits ischemia-induced retinal cell death via its antioxidant effect. Hence, astaxanthin might be effective in treating retinal ischemic pathologies.

Divergent Effects of Losartan and Metoprolol on Cardiac Remodeling, C‐kit+ Cells, Proliferation and Apoptosis in the Left Ventricle after Myocardial Infarction

PubMed Central

Serpi, Raisa; Tolonen, Anna‐Maria; Tenhunen, Olli; Pieviläinen, Oskari; Kubin, Anna‐Maria; Vaskivuo, Tommi; Soini, Ylermi; Kerkelä, Risto; Leskinen, Hanna; Ruskoaho, Heikki

2009-01-01

Abstract There is strong evidence for the use of angiotensin converting enzyme inhibitors and beta‐blockers to reduce morbidity and mortality in patients with myocardial infarction (MI), whereas the effect of angiotensin receptor blockers is less clear. We evaluated the effects of an angiotensin receptor blocker losartan and a beta‐blocker metoprolol on left ventricular (LV) remodeling, c‐kit+ cells, proliferation, fibrosis, apoptosis, and angiogenesis using a model of coronary ligation in rats. Metoprolol treatment for 2 weeks improved LV systolic function. In contrast, losartan triggered deleterious structural remodeling and functional deterioration of LV systolic function, ejection fraction being 41% and fractional shortening 47% lower in losartan group than in controls 2 weeks after MI. The number of c‐kit+ cells as well as expression of Ki‐67 was increased by metoprolol. Losartan‐induced thinning of the anterior wall and ventricular dilation were associated with increased apoptosis and fibrosis, while losartan had no effect on the expression of c‐kit or Ki‐67. Metoprolol or losartan had no effect on microvessel density. These results demonstrate that beta‐blocker treatment attenuated adverse remodeling via c‐kit+ cells and proliferation, whereas angiotensin receptor blocker‐induced worsening of LV systolic function was associated with increased apoptosis and fibrosis in the peri‐infarct region. PMID:20443934

GUCY2D Cone-Rod Dystrophy-6 Is a "Phototransduction Disease" Triggered by Abnormal Calcium Feedback on Retinal Membrane Guanylyl Cyclase 1.

PubMed

Sato, Shinya; Peshenko, Igor V; Olshevskaya, Elena V; Kefalov, Vladimir J; Dizhoor, Alexander M

2018-03-21

The Arg838Ser mutation in retinal membrane guanylyl cyclase 1 (RetGC1) has been linked to autosomal dominant cone-rod dystrophy type 6 (CORD6). It is believed that photoreceptor degeneration is caused by the altered sensitivity of RetGC1 to calcium regulation via guanylyl cyclase activating proteins (GCAPs). To determine the mechanism by which this mutation leads to degeneration, we investigated the structure and function of rod photoreceptors in two transgenic mouse lines, 362 and 379, expressing R838S RetGC1. In both lines, rod outer segments became shorter than in their nontransgenic siblings by 3-4 weeks of age, before the eventual photoreceptor degeneration. Despite the shortening of their outer segments, the dark current of transgenic rods was 1.5-2.2-fold higher than in nontransgenic controls. Similarly, the dim flash response amplitude in R838S + rods was larger, time to peak was delayed, and flash sensitivity was increased, all suggesting elevated dark-adapted free cGMP in transgenic rods. In rods expressing R838S RetGC1, dark-current noise increased and the exchange current, detected after a saturating flash, became more pronounced. These results suggest disrupted Ca 2+ phototransduction feedback and abnormally high free-Ca 2+ concentration in the outer segments. Notably, photoreceptor degeneration, which typically occurred after 3 months of age in R838S RetGC1 transgenic mice in GCAP1,2 +/+ or GCAP1,2 +/- backgrounds, was prevented in GCAP1,2 -/- mice lacking Ca 2+ feedback to guanylyl cyclase. In summary, the dysregulation of guanylyl cyclase in RetGC1-linked CORD6 is a "phototransduction disease," which means it is associated with increased free-cGMP and Ca 2+ levels in photoreceptors. SIGNIFICANCE STATEMENT In a mouse model expressing human membrane guanylyl cyclase 1 (RetGC1, GUCY2D ), a mutation associated with early progressing congenital blindness, cone-rod dystrophy type 6 (CORD6), deregulates calcium-sensitive feedback of phototransduction to

Phase field approaches of bone remodeling based on TIP

NASA Astrophysics Data System (ADS)

Ganghoffer, Jean-François; Rahouadj, Rachid; Boisse, Julien; Forest, Samuel

2016-01-01

The process of bone remodeling includes a cycle of repair, renewal, and optimization. This adaptation process, in response to variations in external loads and chemical driving factors, involves three main types of bone cells: osteoclasts, which remove the old pre-existing bone; osteoblasts, which form the new bone in a second phase; osteocytes, which are sensing cells embedded into the bone matrix, trigger the aforementioned sequence of events. The remodeling process involves mineralization of the bone in the diffuse interface separating the marrow, which contains all specialized cells, from the newly formed bone. The main objective advocated in this contribution is the setting up of a modeling and simulation framework relying on the phase field method to capture the evolution of the diffuse interface between the new bone and the marrow at the scale of individual trabeculae. The phase field describes the degree of mineralization of this diffuse interface; it varies continuously between the lower value (no mineral) and unity (fully mineralized phase, e.g. new bone), allowing the consideration of a diffuse moving interface. The modeling framework is the theory of continuous media, for which field equations for the mechanical, chemical, and interfacial phenomena are written, based on the thermodynamics of irreversible processes. Additional models for the cellular activity are formulated to describe the coupling of the cell activity responsible for bone production/resorption to the kinetics of the internal variables. Kinetic equations for the internal variables are obtained from a pseudo-potential of dissipation. The combination of the balance equations for the microforce associated to the phase field and the kinetic equations lead to the Ginzburg-Landau equation satisfied by the phase field with a source term accounting for the dissipative microforce. Simulations illustrating the proposed framework are performed in a one-dimensional situation showing the evolution of

Retinal pigment epithelium culture;a potential source of retinal stem cells.

PubMed

Akrami, Hassan; Soheili, Zahra-Soheila; Khalooghi, Keynoush; Ahmadieh, Hamid; Rezaie-Kanavi, Mojgan; Samiei, Shahram; Davari, Malihe; Ghaderi, Shima; Sanie-Jahromi, Fatemeh

2009-07-01

To establish human retinal pigment epithelial (RPE) cell culture as a source for cell replacement therapy in ocular diseases. Human cadaver globes were used to isolate RPE cells. Each globe was cut into several pieces of a few millimeters in size. After removing the sclera and choroid, remaining tissues were washed in phosphate buffer saline and RPE cells were isolated using dispase enzyme solution and cultured in Dulbecco's Modified Eagle's Medium: Nutrient Mixture F-12 supplemented with 10% fetal calf serum. Primary cultures of RPE cells were established and spheroid colonies related to progenitor/stem cells developed in a number of cultures. The colonies included purely pigmented or mixed pigmented and non-pigmented cells. After multiple cellular passages, several types of photoreceptors and neural-like cells were detected morphologically. Cellular plasticity in RPE cell cultures revealed promising results in terms of generation of stem/progenitor cells from human RPE cells. Whether the spheroids and neural-like retinal cells were directly derived from retinal stem cells or offspring of trans-differentiating or de-differentiating RPE cells remains to be answered.

RETINAL DISEASES IN A TERTIARY HOSPITAL IN SOUTHERN NIGERIA.

PubMed

Uhumwangho, O M; Itina, E I

2015-01-01

Retinal diseases are an important and common cause of ophthalmic consultation. To determine the pattern of retinal diseases in the ophthalmic department of a tertiary hospital in Southern Nigeria. A retrospective review of the case folders of patients with retinal pathologies seen between 2012 and 2013 was performed. Relevant demographic and clinical data was recorded. Analysis was performed for frequencies, proportions and percentages with the GraphPad Instat Software, Inc. version V2.05a program, San Diego, CA. There were 185 patients made of 94 (50.8%) males and 91 (49.2%) females with a peak age group of 61-70 years, (range 1-85 years) who made consultations for retinal diseases. Age related macular degeneration, 37(15.0%), and macula hole, 10(4.0%), were the common macula pathologies while retinal detachment, 11(4.5%), was the most common condition that required emergency vitreo-retinal surgical intervention. Diabetic retinopathy/maculopathy, 31(12.6%), hypertensive retinopathy 22(8.9%), and retinal vascular occlusion 12(4.8%), were the common retinal vascular diseases found. Bilateral visual impairment (low vision and blindness) from retinal diseases was present in 28(14.4%) persons. The common vitreo-retinal treatment options were use of intravitreal antivascular endothelial growth factors 32(13.0%), laser 16(6.5%), and vitreoretinal surgery in 22(8.9%) eyes. Retinal diseases remain an important cause of ophthalmic consultation and visual loss. Provision of facilities to manage these conditions will improve service delivery and quality of lives of affected patients.

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

Adaptive Optics Technology for High-Resolution Retinal Imaging

PubMed Central

Lombardo, Marco; Serrao, Sebastiano; Devaney, Nicholas; Parravano, Mariacristina; Lombardo, Giuseppe

2013-01-01

Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effects of optical aberrations. The direct visualization of the photoreceptor cells, capillaries and nerve fiber bundles represents the major benefit of adding AO to retinal imaging. Adaptive optics is opening a new frontier for clinical research in ophthalmology, providing new information on the early pathological changes of the retinal microstructures in various retinal diseases. We have reviewed AO technology for retinal imaging, providing information on the core components of an AO retinal camera. The most commonly used wavefront sensing and correcting elements are discussed. Furthermore, we discuss current applications of AO imaging to a population of healthy adults and to the most frequent causes of blindness, including diabetic retinopathy, age-related macular degeneration and glaucoma. We conclude our work with a discussion on future clinical prospects for AO retinal imaging. PMID:23271600

Ischaemia-reperfusion injury in central retinal artery occlusion.

PubMed

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-10-21

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90.

Role of Hydrogen Sulfide in Retinal Diseases.

PubMed

Du, Jiantong; Jin, Hongfang; Yang, Liu

2017-01-01

As the third gasotransmitter, hydrogen sulfide (H 2 S) plays a crucial role in the physiology and pathophysiology of many systems in the body, such as the nervous, cardiovascular, respiratory, and gastrointestinal systems. The mechanisms for its effects, including inhibiting ischemic injury, reducing oxidative stress damage, regulating apoptosis, and reducing the inflammation reaction in different systems, have not been fully understood. Recently, H 2 S and its endogenous synthesis pathway were found in the mammalian retina. This review describes the production and the metabolism of H 2 S and the evidence of a role of H 2 S in the retina physiology and in the different retinal diseases, including retinal degenerative diseases and vascular diseases. In the retina, H 2 S is generated in the presence of cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase from L-cysteine. The role of endogenous H 2 S and its physiologic effect in the retina are still elusive. However, strong evidence shows that retina-derived H 2 S might play protective or deleterious role in the pathogenesis of retinal diseases. For example, by regulating Ca 2+ influx, H 2 S can protect retinal neurons against light-induced degeneration. H 2 S preconditioning can mediate the anti-apoptotic effect of retinal ganglion cells in retinal ischemia/reperfusion injury. Treatment with H 2 S in rats relieves diabetic retinopathy by suppressing oxidative stress and reducing inflammation. Further studies would greatly improve our understanding of the pathophysiologic mechanisms responsible for retinal diseases and the potential for the H 2 S-related therapy of the retinal diseases as well.

Retinal Image Quality During Accommodation

PubMed Central

López-Gil, N.; Martin, J.; Liu, T.; Bradley, A.; Díaz-Muñoz, D.; Thibos, L.

2013-01-01

Purpose We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Methods Subjects viewed a monochromatic (552nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Results Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Conclusions Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye’s higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced

Retinal Optical Coherence Tomography Imaging

NASA Astrophysics Data System (ADS)

Drexler, Wolfgang; Fujimoto, James G.

The eye is essentially transparent, transmitting light with only minimal optical attenuation and scattering providing easy optical access to the anterior segment as well as the retina. For this reason, ophthalmic and especially retinal imaging has been not only the first but also most successful clinical application for optical coherence tomography (OCT). This chapter focuses on the development of OCT technology for retinal imaging. OCT has significantly improved the potential for early diagnosis, understanding of retinal disease pathogenesis, as well as monitoring disease progression and response to therapy. Development of ultrabroad bandwidth light sources and high-speed detection techniques has enabled significant improvements in ophthalmic OCT imaging performance, demonstrating the potential of three-dimensional, ultrahigh-resolution OCT (UHR OCT) to perform noninvasive optical biopsy of the living human retina, i.e., the in vivo visualization of microstructural, intraretinal morphology in situ approaching the resolution of conventional histopathology. Significant improvements in axial resolution and speed not only enable three-dimensional rendering of retinal volumes but also high-definition, two-dimensional tomograms, topographic thickness maps of all major intraretinal layers, as well as volumetric quantification of pathologic intraretinal changes. These advances in OCT technology have also been successfully applied in several animal models of retinal pathologies. The development of light sources emitting at alternative wavelengths, e.g., around #1,060 nm, not only enabled three-dimensional OCT imaging with enhanced choroidal visualization but also improved OCT performance in cataract patients due to reduced scattering losses in this wavelength region. Adaptive optics using deformable mirror technology, with unique high stroke to correct higher-order ocular aberrations, with specially designed optics to compensate chromatic aberration of the human eye, in

Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.

PubMed

Hambli, Ridha

2014-01-01

Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone

ATP-dependent chromatin assembly is functionally distinct from chromatin remodeling

PubMed Central

Torigoe, Sharon E; Patel, Ashok; Khuong, Mai T; Bowman, Gregory D; Kadonaga, James T

2013-01-01

Chromatin assembly involves the combined action of ATP-dependent motor proteins and histone chaperones. Because motor proteins in chromatin assembly also function as chromatin remodeling factors, we investigated the relationship between ATP-driven chromatin assembly and chromatin remodeling in the generation of periodic nucleosome arrays. We found that chromatin remodeling-defective Chd1 motor proteins are able to catalyze ATP-dependent chromatin assembly. The resulting nucleosomes are not, however, spaced in periodic arrays. Wild-type Chd1, but not chromatin remodeling-defective Chd1, can catalyze the conversion of randomly-distributed nucleosomes into periodic arrays. These results reveal a functional distinction between ATP-dependent nucleosome assembly and chromatin remodeling, and suggest a model for chromatin assembly in which randomly-distributed nucleosomes are formed by the nucleosome assembly function of Chd1, and then regularly-spaced nucleosome arrays are generated by the chromatin remodeling activity of Chd1. These findings uncover an unforeseen level of specificity in the role of motor proteins in chromatin assembly. DOI: http://dx.doi.org/10.7554/eLife.00863.001 PMID:23986862

ATP-dependent chromatin remodeling in T cells

PubMed Central

Wurster, Andrea L.; Pazin, Michael J.

2012-01-01

One of the best studied systems for mammalian chromatin remodeling is transcriptional regulation during T cell development. The variety of these studies have led to important findings in T cell gene regulation and cell fate determination. Importantly, these findings have also advanced our knowledge of the function of remodeling enzymes in mammalian gene regulation. In this review, first we briefly present biochemical/cell-free analysis of 3 types of ATP dependent remodeling enzymes (SWI/SNF, Mi2, and ISWI), to construct an intellectual framework to understand how these enzymes might be working. Second, we compare and contrast the function of these enzymes, during early (thymic) and late (peripheral) T cell development. Finally, we examine some of the gaps in our present understanding. PMID:21999456

ATP-dependent chromatin remodeling in T cells.

PubMed

Wurster, Andrea L; Pazin, Michael J

2012-02-01

One of the best studied systems for mammalian chromatin remodeling is transcriptional regulation during T cell development. The variety of these studies have led to important findings in T cell gene regulation and cell fate determination. Importantly, these findings have also advanced our knowledge of the function of remodeling enzymes in mammalian gene regulation. First we briefly present biochemical and cell-free analysis of 3 types of ATP dependent remodeling enzymes (SWI/SNF, Mi2, and ISWI) to construct an intellectual framework to understand how these enzymes might be working. Second, we compare and contrast the function of these enzymes during early (thymic) and late (peripheral) T cell development. Finally, we examine some of the gaps in our present understanding.

Inner neural retina loss in central retinal artery occlusion.

PubMed

Ikeda, Fumiko; Kishi, Shoji

2010-09-01

To report morphologic retinal changes and visual outcomes in acute and chronic central retinal artery occlusion (CRAO). We reviewed ten eyes of ten patients with CRAO (age, 65.3 ± 10.2 years) and measured retinal thicknesses at the central fovea and the perifovea using optical coherence tomography (OCT) over 8 ± 4 months. During the acute phase (within 10 days), the mean inner retinal thicknesses were 148% and 139% of normal values at 1 mm nasal and temporal to the fovea. They decreased to 22% and 11% of normal inner retinal thickness during the chronic phase (3 months or later). The retinal thickness at the perifovea decreased linearly until 3 months but was stable during the chronic phase. In contrast, the foveal thickness increased slightly in the acute phase but was equivalent to the normal level during the chronic phase. As a result of inner retinal atrophy, the foveal pit was shallow during the chronic phase. The final visual acuity was correlated positively with retinal thickness at the perifovea during the chronic CRAO phase. OCT showed that inner retinal necrosis with early swelling and late atrophy occurred in CRAO. The fovea and outer retina appeared to be excluded from ischemic change. The residual inner retina at the perifovea determined the final visual outcomes.

Alteration of Developmental and Pathological Retinal Angiogenesis in angptl4-deficient Mice*

PubMed Central

Perdiguero, Elisa Gomez; Galaup, Ariane; Durand, Mélanie; Teillon, Jérémie; Philippe, Josette; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.; Thurston, Gavin; Germain, Stéphane

2011-01-01

Proper vessel maturation, remodeling of endothelial junctions, and recruitment of perivascular cells is crucial for establishing and maintaining vessel functions. In proliferative retinopathies, hypoxia-induced angiogenesis is associated with disruption of the vascular barrier, edema, and vision loss. Therefore, identifying factors that regulate vascular maturation is critical to target pathological angiogenesis. Given the conflicting role of angiopoietin-like-4 (ANGPTL4) reported in the current literature using gain of function systems both in vitro and in vivo, the goal of this study was to characterize angiogenesis, focusing on perinatal retinal vascularization and pathological circumstances in angpl4-deficient mice. We report altered organization of endothelial junctions and pericyte coverage, both leading to impaired angiogenesis and increased vascular leakage that were eventually caught up, suggesting a delay in vessel maturation. In a model of oxygen-induced retinopathy, pathological neovascularization, which results from tissue hypoxia, was also strongly inhibited in angptl4-deficient mice. This study therefore shows that ANGPTL4 tunes endothelial cell junction organization and pericyte coverage and controls vascular permeability and angiogenesis, both during development and in pathological conditions. PMID:21832056

Coats-like retinitis pigmentosa: Reports of three cases.

PubMed

Kan, Emrah; Yilmaz, Turgut; Aydemir, Orhan; Güler, Mete; Kurt, Jülide

2007-06-01

Describing the ophthalmic findings of an exudative vasculopathy called as Coats-like retinitis pigmentosa on three patients. The etiology of the Coats-like retinitis pigmentosa is obscure. The principal theories have been discussed in this article. Three observational case series have been discussed. Complete ophthalmic examinations and color fundus photos, visual field, and fluorescein angiography have been performed. We have identified 3 patients who have some typical clinical features of Coats-like retinitis pigmentosa; peripheral serous retinal detachment, telangiectasia, prominent lipid deposition, pigmentary changes in peripheral retina, and loss of vision. None of the three patients had positive family history. All of the patients have had symptoms of nyctalopia, decreased central vision, and two of them have had constriction of visual field. All of the patients have had cataracts and two of them underwent cataract surgery. Fundus examination and fluorescein angiography of patients revealed typical retinitis pigmentosa with Coats-type changes in bilateral inferiotemporal quadrants. A better understanding of clinical features and genetic etiology of Coats-type retinitis pigmentosa will aid diagnosis and development of new therapies. If sufficient conditions arise, genetic factors that influence the expression of CRB1 mutations in Coats-like retinitis pigmentosa should be detected.

Retinal tear: an unusual complication of ocular toxoplasmosis.

PubMed

Celebi, Ali Riza Cenk; Kilavuzoglu, Ayse Ebru; Altiparmak, Ugur Emrah; Cosar, Cemile Banu; Ozkiris, Abdullah

2015-01-01

It is aimed to report on a 16-year-old patient with acquired ocular toxoplasmosis complicated by a retinal tear. Retrospective medical chart review. A 16-year-old Caucasian female presented with vision loss in her right eye. In addition to a white active lesion between the fovea and the optic nerve head, marked vitreous opacification was noted. She was diagnosed with ocular toxoplasmosis. The patient was treated with oral azithromycin, clindamycin, and trimethoprimsulfamethoxazole. One month later, retinochoroiditis resolved and vitreous cleared. Three months after onset, patient presented with floaters in the right eye and a retinal tear was located at the temporal region of the retina. Prophylactic argon laser treatment that encircled the retinal tear was performed. No other abnormalities were noted during 6 months of follow-up. Retinal tear associated with ocular toxoplasmosis is rare; however, a retinal tear can occur due to vitreoretinal traction following post-inflammatory structural alteration of the vitreous. Retinal tears may be seen during the healing phase, when the inflammation turns into tightening of vitreous substance. Careful retinal examination in cases of ocular toxoplasmosis is warranted, especially in patients with severe vitreous inflammation.

Retinal diseases in a tertiary hospital: the need for establishment of a vitreo-retinal care unit.

PubMed

Onakpoya, Oluwatoyin Helen; Olateju, Samuel Oluremi; Ajayi, Iyiade Adeseye

2008-11-01

To evaluate the need for vitreo-retinal care for suburban and rural communities of southwestern Nigeria. A retrospective review of patients with posterior segment diseases attending the general ophthalmology clinics of Obafemi Awolowo University Teaching Hospital's complex, Ile Ife, southwestern Nigeria, between January 2001 and December 2006 was conducted. The age, sex and diagnosis were analyzed and needs assessment conducted. Three-thousand, one-hundred-thirty-one new cases were reviewed of which 407(13%) patients presented with retinal diseases. Their mean age was 46.3 +/- 21.4 years, mode 60 years and male:female ratio 1.3:1 (P=0.05). Macula diseases (35.6%), hypertensive retinopathy (12%), retinochoroiditis (11.5%) and diabetic retinopathy (9.6%) were the predominant retinal diseases. Age-related macular degeneration was the most frequent of the macular diseases (38.6%), with a female preponderance (p=0.06). It is estimated that fundus photography +/- fluorescein will be beneficial in 89.4%, laser photocoagulation in 36.4% and vitreo-retinal surgical procedure in 16.4%. Posterior segment diseases are not uncommon in rural communities of southwestern Nigeria. Facilities for fundus angiography, laser photocoagulation and a vitreoretinal surgical unit in trained hands will improve the capacity for specific diagnosis and appropriate management of vitreo-retinal diseases in these communities.

Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration.

PubMed

Inoue, Yuji; Iriyama, Aya; Ueno, Shuji; Takahashi, Hidenori; Kondo, Mineo; Tamaki, Yasuhiro; Araie, Makoto; Yanagi, Yasuo

2007-08-01

Because there is no effective treatment for this retinal degeneration, potential application of cell-based therapy has attracted considerable attention. Several investigations support that bone marrow mesenchymal stem cells (MSCs) can be used for a broad spectrum of indications. Bone marrow MSCs exert their therapeutic effect in part by secreting trophic factors to promote cell survival. The current study investigates whether bone marrow MSCs secrete factor(s) to promote photoreceptor cell survival and whether subretinal transplantation of bone marrow MSCs promotes photoreceptor survival in a retinal degeneration model using Royal College of Surgeons (RCS) rats. In vitro, using mouse retinal cell culture, it was demonstrated that the conditioned medium of the MSCs delays photoreceptor cell apoptosis, suggesting that the secreted factor(s) from the MSCs promote photoreceptor cell survival. In vivo, the MSCs were injected into the subretinal space of the RCS rats and histological analysis, real-time RT-PCR and electrophysiological analysis demonstrated that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function in the RCS rats. These results suggest that MSC is a useful cell source for cell-replacement therapy for some forms of retinal degeneration.

Optical Coherence Tomography Angiography in Retinal Diseases.

PubMed

Chalam, K V; Sambhav, Kumar

2016-01-01

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases.

Optical Coherence Tomography Angiography in Retinal Diseases

PubMed Central

Chalam, K. V.; Sambhav, Kumar

2016-01-01

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID:27195091

Screening retinal transplants with Fourier-domain OCT

NASA Astrophysics Data System (ADS)

Rao, Bin

2009-02-01

Transplant technologies have been studied for the recovery of vision loss from retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In several rodent retinal degeneration models and in patients, retinal progenitor cells transplanted as layers to the subretinal space have been shown to restore or preserve vision. The methods for evaluation of transplants are expensive considering the large amount of animals. Alternatively, time-domain Stratus OCT was previously shown to be able to image the morphological structure of transplants to some extent, but could not clearly identify laminated transplants. The efficacy of screening retinal transplants with Fourier-domain OCT was studied on 37 S334ter line 3 rats with retinal degeneration 6-67 days after transplant surgery. The transplants were morphologically categorized as no transplant, detachment, rosettes, small laminated area and larger laminated area with both Fourier-domain OCT and histology. The efficacy of Fourier-domain OCT in screening retinal transplants was evaluated by comparing the categorization results with OCT and histology. Additionally, 4 rats were randomly selected for multiple OCT examinations (1, 5, 9, 14 and 21days post surgery) in order to determine the earliest image time of OCT examination since the transplanted tissue may need some time to show its tendency of growing. Finally, we demonstrated the efficacy of Fourier-domain OCT in screening retinal transplants in early stages and determined the earliest imaging time for OCT. Fourier-domain OCT makes itself valuable in saving resource spent on animals with unsuccessful transplants.

Retinoids and Retinal Diseases

PubMed Central

Kiser, Philip D.; Palczewski, Krzysztof

2016-01-01

Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or engineered animal models with known genetic lesions and studies of humans with specific genetic blinding diseases. Structural and membrane biology have been used to detect critical retinal enzymes and proteins and their substrates and ligands, placing them in a cellular context. These studies have been supplemented by analytical chemistry methods that have identified small molecules by their spectral characteristics, often in conjunction with the evaluation of models of animal retinal disease. It is from this background that rational therapeutic interventions to correct genetic defects or environmental insults are identified. Thus, most presently accepted modulators of the retinoid cycle already have demonstrated promising results in animal models of retinal degeneration. These encouraging signs indicate that some human blinding diseases can be alleviated by pharmacological interventions. PMID:27917399

Treatment of laser-induced retinal injuries by neuroprotection

NASA Astrophysics Data System (ADS)

Solberg, Yoram; Rosner, Mordechai; Belkin, Michael

1997-05-01

Retinal laser photocoagulation treatments are often complicated with immediate side-effect of visual impairment. To determine whether glutamate-receptor blockers can serve as adjuvant neuroprotective therapy, we examined the effect of MK-801, an NMDA-receptor antagonist, on laser-induced retinal injury in a rat model. Argon laser retinal lesions were created in the retina of 36 DA rats. Treatment with intraperitoneal injections of MK-801 or saline was started immediately after the laser photocoagulation. The animals were sacrificed after 3, 20 or 60 days and the retinal lesions were evaluated histologically and morphometrically. Photoreceptor-cell loss was significantly smaller in MK-801-treated rats than controls. The proliferative membrane composed of retinal pigment epithelial cells which was seen at the base of the lesion in control retinas, was smaller in the MK-801-treated retinas. MK-801 exhibited neuroprotective and anti-proliferative properties in the retina. Glutamate-receptor blockers should be further investigated for serving as adjuvant therapy to retinal photocoagulation treatments.

Ischaemia-reperfusion injury in central retinal artery occlusion

PubMed Central

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-01-01

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90. PMID:24145508

Oxygen-induced retinopathy in mice with retinal photoreceptor cell degeneration.

PubMed

Zhang, Qian; Zhang, Zuo-Ming

2014-04-25

It is reported that retinal neovascularization seems to rarely co-exist with retinitis pigmentosa in patients and in some mouse models; however, it is not widely acknowledged as a universal phenomenon in all strains of all animal species. We aimed to further explore this phenomenon with an oxygen-induced retinopathy model in mice with retinal photoreceptor cell degeneration. Oxygen-induced retinopathy of colored and albino mice with rapid retinal degeneration were compared to homologous wild-type mice. The retinas were analyzed using high-molecular-weight FITC-dextran stained flat-mount preparation, hematoxylin and eosin (H&E) stained cross-sections, an immunohistochemical test for vascular endothelial growth factor (VEGF) distribution and Western blotting for VEGF expression after exposure to hyperoxia between postnatal days 17 (P17) and 21. Leakage and areas of non-perfusion of the retinal blood vessels were alleviated in the retinal degeneration mice. The number of preretinal vascular endothelial cell nuclei in the retinal degeneration mice was smaller than that in the homologous wild-type mice after exposure to hyperoxia (P<0.01). The degree of oxygen-induced retinopathy was positively correlated with the VEGF expression level. However, the VEGF expression level was lower in the retinal degeneration mice. Proliferative retinopathy occurred in mice with rapid retinal degeneration, but retinal photoreceptor cell degeneration could partially restrain the retinal neovascularization in this rapid retinal degeneration mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of Infrared Laser Radiation on the In Vitro Isomerization of All-Trans Retinal to 11-Cis Retinal

PubMed Central

Liegner, J.; Taboada, J.; Tsin, A. T. C.

2015-01-01

The in vitro effect of infrared laser light on the isomerization of all-trans retinal dissolved in an ether/hexane and also an ethanol solvent was studied. Pulsed laser energy at 1064 nm was used to drive the molecular reconfiguration of all-trans retinal to 11-cis retinal. High pressure liquid chromatography (HPLC) was used to quantify the conversion. Overall isomerization was minimal (0.2 percent to 1.0 percent), yet, a significant difference in isomerization due to pulsed infrared laser energy over non-modulated monochromatic laser light was detected (up to 168 percent difference). Potentially, pulsed laser radiation tuned to the ethylenic stretch frequency of the C11=C12 bond of retinal may induce rotational changes to the chromophore. PMID:26321787

Simulation Study of an Ultrasound Retinal Prosthesis With a Novel Contact-Lens Array for Noninvasive Retinal Stimulation.

PubMed

Gao, Mengdi; Yu, Yanyan; Zhao, Huixia; Li, Guofeng; Jiang, Hongyang; Wang, Congzhi; Cai, Feiyan; Chan, Leanne Lai-Hang; Chiu, Bernard; Qian, Wei; Qiu, Weibao; Zheng, Hairong

2017-09-01

Millions of people around the world suffer from varying degrees of vision loss (including complete blindness) because of retinal degenerative diseases. Artificial retinal prosthesis, which is usually based on electrical neurostimulation, is the most advanced technology for different types of retinal degeneration. However, this technology involves placing a device into the eyeball, and such a highly invasive procedure is inevitably highly risk and expensive. Ultrasound has been demonstrated to be a promising technology for noninvasive neurostimulation, making it possible to stimulate the retina and induce action potentials similar to those elicited by light stimulation. However, the technology of ultrasound retinal stimulation still requires considerable developments before it could be applied clinically. This paper proposes a novel contact-lens array transducer for use in an ultrasound retinal prosthesis (USRP). The transducer was designed in the shape of a contact lens so as to facilitate acoustic coupling with the eye liquid. The key parameters of the ultrasound transducer were simulated, and results are presented that indicate the achievement of 2-D pattern generation and that the proposed contact-lens array is suitable for multiple-focus neurostimulation, and can be used in a USRP.

Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

PubMed Central

Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

2015-01-01

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

Low Vision Rehabilitation of Retinitis Pigmentosa. Practice Report

ERIC Educational Resources Information Center

Rundquist, John

2004-01-01

Retinitis pigmentosa is a rod-cone dystrophy, commonly genetic in nature. Approximately 60-80% of those with retinitis pigmentosa inherit it by an autosomal recessive transmission (Brilliant, 1999). There have been some reported cases with no known family history. The symptoms of retinitis pigmentosa are decreased acuity, photophobia, night…

Inherited Retinal Degenerative Clinical Trial Network. Addendum

DTIC Science & Technology

2013-10-01

visual impairment usually ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa , and the ProgSTAR studies for Stargardt disease) . As new interventions b... retinitis pigmentosa continues at six sites- the CTEC site at University of Utah and five additional recruitment sites- the Retina Foundation of the

Left ventricular remodeling in preclinical experimental mitral regurgitation of dogs.

PubMed

Dillon, A Ray; Dell'Italia, Louis J; Tillson, Michael; Killingsworth, Cheryl; Denney, Thomas; Hathcock, John; Botzman, Logan

2012-03-01

Dogs with experimental mitral regurgitation (MR) provide insights into the left ventricular remodeling in preclinical MR. The early preclinical left ventricular (LV) changes after mitral regurgitation represent progressive dysfunctional remodeling, in that no compensatory response returns the functional stroke volume (SV) to normal even as total SV increases. The gradual disease progression leads to mitral annulus stretch and enlargement of the regurgitant orifice, further increasing the regurgitant volume. Remodeling with loss of collagen weave and extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the cross-sectional area and length of the cardiomyocyte. Isolated ventricular cardiomyocytes demonstrate dysfunction based on decreased cell shortening and reduced intracellular calcium transients before chamber enlargement or decreases in contractility in the whole heart can be clinically appreciated. The genetic response to increased end-diastolic pressure is down-regulation of genes associated with support of the collagen and ECM and up-regulation of genes associated with matrix remodeling. Experiments have not demonstrated any beneficial effects on remodeling from treatments that decrease afterload via blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase inhibition have altered the progression of the LV remodeling and have supported cardiomyocyte function. The geometry of the LV during the remodeling provides insight into the importance of regional differences in responses to wall stress. Copyright © 2012 Elsevier B.V. All rights reserved.

Clinical Features of Newly Diagnosed Cytomegalovirus Retinitis in Northern Thailand

PubMed Central

Ausayakhun, Somsanguan; Keenan, Jeremy D; Ausayakhun, Sakarin; Jirawison, Choeng; Khouri, Claire M; Skalet, Alison H; Heiden, David; Holland, Gary N; Margolis, Todd P

2011-01-01

Purpose To characterize the clinical manifestations of cytomegalovirus (CMV) retinitis in northern Thailand. Design Prospective, observational cross-sectional study. Methods We recorded characteristics of 52 consecutive patients newly diagnosed with CMV retinitis at a tertiary university-based medical center in northern Thailand. Indirect ophthalmoscopy by experienced ophthalmologists was supplemented with fundus photography to determine the proportion of eyes with various clinical features of CMV retinitis. Results Of the 52 patients with CMV retinitis, 55.8% were female. All were HIV-positive. The vast majority (90.4%) had started antiretroviral therapy. CMV retinitis was bilateral in 46.2% of patients. Bilateral visual acuity worse than 20/60 was observed in 23.1% of patients. Of 76 eyes with CMV retinitis, 61.8% had zone I disease and 21.6% had lesions involving the fovea. Lesions larger than 25% of the retinal area were observed in 57.5% of affected eyes. CMV retinitis lesions commonly had marked or severe border opacity (47.4% of eyes). Vitreous haze was often present (46.1% of eyes). Visual impairment was more common in eyes with larger retinitis lesions. Retinitis lesion size, used as a proxy for duration of disease, was associated with fulminant appearance (OR 1.24 [1.01 – 1.51]), and marked or severe border opacity (OR 1.36 [1.11 – 1.67]). Based on lesion size, retinitis preceded antiretroviral treatment in each patient. Conclusions Patients presenting to a tertiary medical center in northern Thailand have advanced CMV retinitis, possibly due to delayed diagnosis. Earlier screening and treatment of CMV retinitis may limit progression of disease and prevent visual impairment in this population. PMID:22265148

Layer-specific blood-flow MRI of retinitis pigmentosa in RCS rats☆

PubMed Central

Li, Guang; Garza, Bryan De La; Shih, Yen-Yu I.; Muir, Eric R.; Duong, Timothy Q.

2013-01-01

The Royal College of Surgeons (RCS) rat is an established animal model of retinitis pigmentosa, a family of inherited retinal diseases which starts with loss of peripheral vision and progresses to eventual blindness. Blood flow (BF), an important physiological parameter, is intricately coupled to metabolic function under normal physiological conditions and is perturbed in many neurological and retinal diseases. This study reports non-invasive high-resolution MRI (44 × 44 × 600 μm) to image quantitative retinal and choroidal BF and layer-specific retinal thicknesses in RCS rat retinas at different stages of retinal degeneration compared with age-matched controls. The unique ability to separate retinal and choroidal BF was made possible by the depth-resolved MRI technique. RBF decreased with progressive retinal degeneration, but ChBF did not change in RCS rats up to post-natal day 90. We concluded that choroidal and retinal circulations have different susceptibility to progressive retinal degeneration in RCS rats. Layer-specific retinal thickness became progressively thinner and was corroborated by histological analysis in the same animals. MRI can detect progressive anatomical and BF changes during retinal degeneration with laminar resolution. PMID:22721720

Layer-specific blood-flow MRI of retinitis pigmentosa in RCS rats.

PubMed

Li, Guang; De La Garza, Bryan; Shih, Yen-Yu I; Muir, Eric R; Duong, Timothy Q

2012-08-01

The Royal College of Surgeons (RCS) rat is an established animal model of retinitis pigmentosa, a family of inherited retinal diseases which starts with loss of peripheral vision and progresses to eventual blindness. Blood flow (BF), an important physiological parameter, is intricately coupled to metabolic function under normal physiological conditions and is perturbed in many neurological and retinal diseases. This study reports non-invasive high-resolution MRI (44 × 44 × 600 μm) to image quantitative retinal and choroidal BF and layer-specific retinal thicknesses in RCS rat retinas at different stages of retinal degeneration compared with age-matched controls. The unique ability to separate retinal and choroidal BF was made possible by the depth-resolved MRI technique. RBF decreased with progressive retinal degeneration, but ChBF did not change in RCS rats up to post-natal day 90. We concluded that choroidal and retinal circulations have different susceptibility to progressive retinal degeneration in RCS rats. Layer-specific retinal thickness became progressively thinner and was corroborated by histological analysis in the same animals. MRI can detect progressive anatomical and BF changes during retinal degeneration with laminar resolution. Copyright © 2012 Elsevier Ltd. All rights reserved.

Retinal adaptation to dim light vision in spectacled caimans (Caiman crocodilus fuscus): Analysis of retinal ultrastructure.

PubMed

Karl, Anett; Agte, Silke; Zayas-Santiago, Astrid; Makarov, Felix N; Rivera, Yomarie; Benedikt, Jan; Francke, Mike; Reichenbach, Andreas; Skatchkov, Serguei N; Bringmann, Andreas

2018-05-19

It has been shown that mammalian retinal glial (Müller) cells act as living optical fibers that guide the light through the retinal tissue to the photoreceptor cells (Agte et al., 2011; Franze et al., 2007). However, for nonmammalian species it is unclear whether Müller cells also improve the transretinal light transmission. Furthermore, for nonmammalian species there is a lack of ultrastructural data of the retinal cells, which, in general, delivers fundamental information of the retinal function, i.e. the vision of the species. A detailed study of the cellular ultrastructure provides a basic approach of the research. Thus, the aim of the present study was to investigate the retina of the spectacled caimans at electron and light microscopical levels to describe the structural features. For electron microscopy, we used a superfast microwave fixation procedure in order to achieve more precise ultrastructural information than common fixation techniques. As result, our detailed ultrastructural study of all retinal parts shows structural features which strongly indicate that the caiman retina is adapted to dim light and night vision. Various structural characteristics of Müller cells suppose that the Müller cell may increase the light intensity along the path of light through the neuroretina and, thus, increase the sensitivity of the scotopic vision of spectacled caimans. Müller cells traverse the whole thickness of the neuroretina and thus may guide the light from the inner retinal surface to the photoreceptor cell perikarya and the Müller cell microvilli between the photoreceptor segments. Thick Müller cell trunks/processes traverse the layers which contain light-scattering structures, i.e., nerve fibers and synapses. Large Müller cell somata run through the inner nuclear layer and contain flattened, elongated Müller cell nuclei which are arranged along the light path and, thus, may reduce the loss of the light intensity along the retinal light path. The

Retinal single-layer analysis with optical coherence tomography shows inner retinal layer thinning in Huntington's disease as a potential biomarker.

PubMed

Gulmez Sevim, Duygu; Unlu, Metin; Gultekin, Murat; Karaca, Cagatay

2018-02-12

There have been ongoing clinical trials of therapeutic agents in Huntington's disease (HD) which requires development of reliable biomarkers of disease progression. There have been studies in the literature with conflicting results on the involvement of retina in HD, and up to date there is not a study evaluating the single retinal layers in HD. We aimed to evaluate the specific retinal changes in HD and their usability as potential disease progression markers. This cross-sectional study used spectral-domain optical coherence tomography with automatic segmentation to measure peripapillary retinal nerve fiber layer (pRNFL) thickness and the thickness and volume of retinal layers in foveal scans of 15 patients with HD and 15 age- and sex-matched controls. Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scales motor scores were acquired for the patients. Temporal pRNFL, macular RNFL (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer and outer plexiform layer thicknesses and IPL, retinal pigment epithelium and outer macular volume were found lower in HD compared to controls, while outer nuclear layer and outer retinal layer thickness were increased (p < 0.05). We found significant correlations between inner retinal layer thicknesses, most significantly with mRNFL and GCL and disease progression markers. The outcomes of this study points out that retinal layers, most significantly mRNFL and GCL, are strongly correlated with the disease progression in HD and could serve as useful biomarkers for disease progression.

On the retinal toxicity of intraocular glucocorticoids.

PubMed

Torriglia, Alicia; Valamanesh, Fatemeh; Behar-Cohen, Francine

2010-12-15

Corticosteroids are hormones involved in many physiological responses such as stress, immune modulation, protein catabolism and water homeostasis. The subfamily of glucocorticoids is used systemically in the treatment of inflammatory diseases or allergic reactions. In the eye, glucocorticoides are used to treat macular edema, inflammation and neovascularization. The most commonly used glucocorticoid is triamcinolone acetonide (TA). The pharmaceutical formulation of TA is not adapted for intravitreal administration but has been selected by ophthalmologists because its very low intraocular solubility provides sustained effect. Visual benefits of intraocular TA do not clearly correlate with morpho-anatomical improvements, suggesting potential toxicity. We therefore studied, non-common, but deleterious effects of glucocorticoids on the retina. We found that the intravitreal administration of TA is beneficial in the treatment of neovascularization because it triggers cell death of endothelial cells of neovessels by a caspase-independent mechanism. However, this treatment is toxic for the retina because it induces a non-apoptotic, caspase-independent cell death related to paraptosis, mostly in the retinal pigmented epithelium cells and the Müller cells. Copyright © 2010 Elsevier Inc. All rights reserved.

Regulatory and Economic Considerations of Retinal Drugs.

PubMed

Shah, Ankoor R; Williams, George A

2016-01-01

The advent of anti-VEGF therapy for neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion and diabetes mellitus has prevented blindness in tens of thousands of people. However, the costs of these drugs are without precedent in ophthalmic drug therapeutics. An analysis of the financial implications of retinal drugs and the impact of the Food and Drug Administration on treatment of retinal disease must include not only an evaluation of the direct costs of the drugs and the costs associated with their administration, but also the cost savings which accrue from their clinical benefit. This chapter will discuss the financial and regulatory issues associated with retinal drugs. © 2016 S. Karger AG, Basel.

Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

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

Ostrup, Olga, E-mail: osvarcova@gmail.com; Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo; Norwegian Center for Stem Cell Research, Oslo

Highlights: {yields} Xenopus egg extract remodels nuclei and alter cell growth characteristics. {yields} Ribosomal genes are reprogrammed within 6 h after extract exposure. {yields} rDNA reprogramming involves promoter targeting of SNF2H remodeling complex. {yields} Xenopus egg extract does not initiate stress-related response in somatic cells. {yields} Aza-cytidine elicits a stress-induced response in reprogrammed cells. -- Abstract: Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression.more » This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation of various reprogramming methods.« less

Unilateral retinitis pigmentosa and cone-rod dystrophy

PubMed Central

Farrell, Donald F

2009-01-01

Purpose: The purpose of this paper is to report 14 new cases of unilateral retinitis pigmentosa and three new cases of cone-rod dystrophy and to compare the similarities and dissimilarities to those found in the bilateral forms of these disorders. Methods: A total of 272 cases of retinitis pigmentosa and 167 cases of cone-rod dystrophy were studied by corneal full field electroretinograms and electrooculograms. The student t-test was used to compare categories. Results: The percentage of familial and nonfamilial cases was the same for the bilateral and unilateral forms of the disease. In our series, unilateral retinitis pigmentosa makes up approximately 5% of the total population of retinitis pigmentosa, while unilateral cone-rod dystrophy makes up only about 2% of the total. In the familial forms of unilateral retinitis pigmentosa the most common inheritance pattern was autosomal dominant and all affected relatives had bilateral disease. Conclusion: Unilateral retinitis pigmentosa and cone-rod dystrophy appear to be directly related to the more common bilateral forms of these disorders. The genetic mechanisms which account for asymmetric disorders are not currently understood. It may be a different unidentified mutation at a single loci or it is possible that nonlinked mutations in multiple loci account for this unusual disorder. PMID:19668577

Retinal iron homeostasis in health and disease

PubMed Central

Song, Delu; Dunaief, Joshua L.

2013-01-01

Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Since iron is not excreted from the body, it accumulates with age in tissues, including the retina, predisposing to age-related oxidative insult. Both hereditary and acquired retinal diseases are associated with increased iron levels. For example, retinal degenerations have been found in hereditary iron overload disorders, like aceruloplasminemia, Friedreich's ataxia, and pantothenate kinase-associated neurodegeneration. Similarly, mice with targeted mutation of the iron exporter ceruloplasmin and its homolog hephaestin showed age-related retinal iron accumulation and retinal degeneration with features resembling human age-related macular degeneration (AMD). Post mortem AMD eyes have increased levels of iron in retina compared to age-matched healthy donors. Iron accumulation in AMD is likely to result, in part, from inflammation, hypoxia, and oxidative stress, all of which can cause iron dysregulation. Fortunately, it has been demonstrated by in vitro and in vivo studies that iron in the retinal pigment epithelium (RPE) and retina is chelatable. Iron chelation protects photoreceptors and retinal pigment epithelial cells (RPE) in a variety of mouse models. This has therapeutic potential for diminishing iron-induced oxidative damage to prevent or treat AMD. PMID:23825457

Towards a Completely Implantable, Light-Sensitive Intraocular Retinal Prosthesis

DTIC Science & Technology

2001-10-25

electronic retinal prosthesis is under development to treat retinitis pigmentosa and age-related macular degeneration, two presently incurable...34Preservation of the inner retina in retinitis pigmentosa . A morphometric analysis," Arch Ophthalmol, vol. 115, no. 4, pp. 511-515, Apr.1997...Towards a completely implantable, light-sensitive intraocular retinal prosthesis. M.S. Humayun, J.D. Weiland, B. Justus1, C. Merrit1, J. Whalen, D

Postconditioning with inhaled hydrogen promotes survival of retinal ganglion cells in a rat model of retinal ischemia/reperfusion injury.

PubMed

Wang, Ruobing; Wu, Jiangchun; Chen, Zeli; Xia, Fangzhou; Sun, Qinglei; Liu, Lin

2016-02-01

Retinal ischemia/reperfusion (I/R) injury plays a crucial role in the pathophysiology of various ocular diseases. Intraperitoneal injection or ocular instillation with hydrogen (H2)-rich saline was recently shown to be neuroprotective in the retina due to its anti-oxidative and anti-inflammatory effects. Our study aims to explore whether postconditioning with inhaled H2 can protect retinal ganglion cells (RGCs) in a rat model of retinal I/R injury. Retinal I/R injury was performed on the right eyes of rats and was followed by inhalation of 67% H2 mixed with 33% oxygen immediately after ischemia for 1h daily for one week. RGC density was counted using haematoxylin and eosin (HE) staining and retrograde labeling with cholera toxin beta (CTB). Visual function was assessed using flash visual evoked potentials (FVEP) and pupillary light reflex (PLR). Potential biomarkers of retinal oxidative stress and inflammatory responses were measured, including the expression of 4-Hydroxynonenalv (4-HNE), interleukin-1 beta (IL1-β) and tumor necrosis factor alpha (TNF-α). HE and CTB tracing showed that the survival rate of RGCs in the H2-treated group was significantly higher than the rate in the I/R group. Rats with H2 inhalation showed better visual function in assessments of FVEP and PLR. Moreover, H2 treatment significantly decreased the number of 4-HNE-stained cells in the ganglion cell layer and inhibited the retinal overexpression of IL1-β and TNF-α that was induced by retinal I/R injury. Our results demonstrate that postconditioning with inhaled high-dose H2 appears to confer neuroprotection against retinal I/R injury via anti-oxidative, anti-inflammatory and anti-apoptosis pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential for autoimmune pathogenesis of Rift Valley Fever virus retinitis.

PubMed

Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric; Peters, Clarence J; Morrill, John; Lucas, Alexander H; King, Charles H; Kazura, James; LaBeaud, Angelle Desiree

2013-09-01

Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication.

Potential for Autoimmune Pathogenesis of Rift Valley Fever Virus Retinitis

PubMed Central

Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric; Peters, Clarence J.; Morrill, John; Lucas, Alexander H.; King, Charles H.; Kazura, James; LaBeaud, Angelle Desiree

2013-01-01

Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication. PMID:23918215

Retinal vascular changes are a marker for cerebral vascular diseases

PubMed Central

Moss, Heather E.

2016-01-01

The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

Coats-like retinitis pigmentosa: Reports of three cases

PubMed Central

Kan, Emrah; Yilmaz, Turgut; Aydemir, Orhan; Güler, Mete; Kurt, Jülide

2007-01-01

Purpose: Describing the ophthalmic findings of an exudative vasculopathy called as Coats-like retinitis pigmentosa on three patients. The etiology of the Coats-like retinitis pigmentosa is obscure. The principal theories have been discussed in this article. Methods: Three observational case series have been discussed. Complete ophthalmic examinations and color fundus photos, visual field, and fluorescein angiography have been performed. Results: We have identified 3 patients who have some typical clinical features of Coats-like retinitis pigmentosa; peripheral serous retinal detachment, telangiectasia, prominent lipid deposition, pigmentary changes in peripheral retina, and loss of vision. None of the three patients had positive family history. All of the patients have had symptoms of nyctalopia, decreased central vision, and two of them have had constriction of visual field. All of the patients have had cataracts and two of them underwent cataract surgery. Fundus examination and fluorescein angiography of patients revealed typical retinitis pigmentosa with Coats-type changes in bilateral inferiotemporal quadrants. Conclusion: A better understanding of clinical features and genetic etiology of Coats-type retinitis pigmentosa will aid diagnosis and development of new therapies. If sufficient conditions arise, genetic factors that influence the expression of CRB1 mutations in Coats-like retinitis pigmentosa should be detected. PMID:19668510

Retinal oxygen saturation before and after glaucoma surgery.

PubMed

Nitta, Eri; Hirooka, Kazuyuki; Shimazaki, Takeru; Sato, Shino; Ukegawa, Kaori; Nakano, Yuki; Tsujikawa, Akitaka

2017-08-01

This study compared retinal vessel oxygen saturation before and after glaucoma surgery. Retinal oxygen saturation in glaucoma patients was measured using a non-invasive spectrophotometric retinal oximeter. Adequate image quality was found in 49 of the 108 consecutive glaucoma patients recruited, with 30 undergoing trabeculectomy, 11 EX-PRESS and eight trabeculotomy. Retinal oxygen saturation measurements in the retinal arterioles and venules were performed at 1 day prior to and at approximately 10 days after surgery. Statistical analysis was performed using a Student's t-test. After glaucoma surgery, intraocular pressure (IOP) decreased from 19.8 ± 7.7 mmHg to 9.0 ± 5.7 mmHg (p < 0.001). Although oxygen saturation in retinal arterioles remained unchanged before and after surgery (104.7 ± 10.6% before and 105.4 ± 9.3% after surgery, p = 0.58), the oxygen saturation in the venules increased from 54.9 ± 7.4% to 57.4 ± 5.7% (p = 0.01). Intraocular pressure (IOP) decreases caused by glaucoma surgery had an effect on the retinal venous oxygen saturation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Probabilistic retinal vessel segmentation

NASA Astrophysics Data System (ADS)

Wu, Chang-Hua; Agam, Gady

2007-03-01

Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

ENA/VASP downregulation triggers cell death by impairing axonal maintenance in hippocampal neurons.

PubMed

Franco, D Lorena; Rezával, Carolina; Cáceres, Alfredo; Schinder, Alejandro F; Ceriani, M Fernanda

2010-06-01

Neurodegenerative diseases encompass a broad variety of motor and cognitive disorders that are accompanied by death of specific neuronal populations or brain regions. Cellular and molecular mechanisms underlying these complex disorders remain largely unknown. In a previous work we searched for novel Drosophila genes relevant for neurodegeneration and singled out enabled (ena), which encodes a protein involved in cytoskeleton remodeling. To extend our understanding on the mechanisms of ENA-triggered degeneration we now investigated the effect of silencing ena ortholog genes in mouse hippocampal neurons. We found that ENA/VASP downregulation led to neurite retraction and concomitant neuronal cell death through an apoptotic pathway. Remarkably, this retraction initially affected the axonal structure, showing no effect on dendrites. Reduction in ENA/VASP levels blocked the neuritogenic effect of a specific RhoA kinase (ROCK) inhibitor, thus suggesting that these proteins could participate in the Rho-signaling pathway. Altogether these observations demonstrate that ENA/VASP proteins are implicated in the establishment and maintenance of the axonal structure and that a change on their expression levels triggers neuronal degeneration. 2010 Elsevier Inc. All rights reserved.

Retinal Pigment Epithelium Culture;a Potential Source of Retinal Stem Cells

PubMed Central

Akrami, Hassan; Soheili, Zahra-Soheila; Khalooghi, Keynoush; Ahmadieh, Hamid; Rezaie-Kanavi, Mojgan; Samiei, Shahram; Davari, Malihe; Ghaderi, Shima; Sanie-Jahromi, Fatemeh

2009-01-01

Purpose To establish human retinal pigment epithelial (RPE) cell culture as a source for cell replacement therapy in ocular diseases. Methods Human cadaver globes were used to isolate RPE cells. Each globe was cut into several pieces of a few millimeters in size. After removing the sclera and choroid, remaining tissues were washed in phosphate buffer saline and RPE cells were isolated using dispase enzyme solution and cultured in Dulbecco’s Modified Eagle’s Medium: Nutrient Mixture F-12 supplemented with 10% fetal calf serum. Results Primary cultures of RPE cells were established and spheroid colonies related to progenitor/stem cells developed in a number of cultures. The colonies included purely pigmented or mixed pigmented and non-pigmented cells. After multiple cellular passages, several types of photoreceptors and neural-like cells were detected morphologically. Conclusion Cellular plasticity in RPE cell cultures revealed promising results in terms of generation of stem/progenitor cells from human RPE cells. Whether the spheroids and neural-like retinal cells were directly derived from retinal stem cells or offspring of trans-differentiating or de-differentiating RPE cells remains to be answered. PMID:23198062

Clinical applications of retinal gene therapy.

PubMed

Lipinski, Daniel M; Thake, Miriam; MacLaren, Robert E

2013-01-01

Many currently incurable forms of blindness affecting the retina have a genetic etiology and several others, such as those resulting from retinal vascular disturbances, respond to repeated, potentially indefinite administration of molecular based treatments. The recent clinical advances in retinal gene therapy have shown that viral vectors can deliver genes safely to the retina and the promising initial results from a number of clinical trials suggest that certain diseases may potentially be treatable. Gene therapy provides a means of expressing proteins within directly transduced cells with far greater efficacy than might be achieved by traditional systemic pharmacological approaches. Recent developments have demonstrated how vector gene expression may be regulated and further improvements to vector design have limited side effects and improved safety profiles. These recent steps have been most significant in bringing gene therapy into the mainstream of ophthalmology. Nevertheless translating retinal gene therapy from animal research into clinical trials is still a lengthy process, including complexities in human retinal diseases that have been difficult to model in the laboratory. The focus of this review is to summarize the genetic background of the most common retinal diseases, highlight current concepts of gene delivery technology, and relate those technologies to pre-clinical and clinical gene therapy studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Stem Cell Therapies in Retinal Disorders.

PubMed

Garg, Aakriti; Yang, Jin; Lee, Winston; Tsang, Stephen H

2017-02-02

Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs) have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs) revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients' diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

Deblurring adaptive optics retinal images using deep convolutional neural networks.

PubMed

Fei, Xiao; Zhao, Junlei; Zhao, Haoxin; Yun, Dai; Zhang, Yudong

2017-12-01

The adaptive optics (AO) can be used to compensate for ocular aberrations to achieve near diffraction limited high-resolution retinal images. However, many factors such as the limited aberration measurement and correction accuracy with AO, intraocular scatter, imaging noise and so on will degrade the quality of retinal images. Image post processing is an indispensable and economical method to make up for the limitation of AO retinal imaging procedure. In this paper, we proposed a deep learning method to restore the degraded retinal images for the first time. The method directly learned an end-to-end mapping between the blurred and restored retinal images. The mapping was represented as a deep convolutional neural network that was trained to output high-quality images directly from blurry inputs without any preprocessing. This network was validated on synthetically generated retinal images as well as real AO retinal images. The assessment of the restored retinal images demonstrated that the image quality had been significantly improved.

Deblurring adaptive optics retinal images using deep convolutional neural networks

PubMed Central

Fei, Xiao; Zhao, Junlei; Zhao, Haoxin; Yun, Dai; Zhang, Yudong

2017-01-01

The adaptive optics (AO) can be used to compensate for ocular aberrations to achieve near diffraction limited high-resolution retinal images. However, many factors such as the limited aberration measurement and correction accuracy with AO, intraocular scatter, imaging noise and so on will degrade the quality of retinal images. Image post processing is an indispensable and economical method to make up for the limitation of AO retinal imaging procedure. In this paper, we proposed a deep learning method to restore the degraded retinal images for the first time. The method directly learned an end-to-end mapping between the blurred and restored retinal images. The mapping was represented as a deep convolutional neural network that was trained to output high-quality images directly from blurry inputs without any preprocessing. This network was validated on synthetically generated retinal images as well as real AO retinal images. The assessment of the restored retinal images demonstrated that the image quality had been significantly improved. PMID:29296496

Spectrally optimal illuminations for diabetic retinopathy detection in retinal imaging

NASA Astrophysics Data System (ADS)

Bartczak, Piotr; Fält, Pauli; Penttinen, Niko; Ylitepsa, Pasi; Laaksonen, Lauri; Lensu, Lasse; Hauta-Kasari, Markku; Uusitalo, Hannu

2017-04-01

Retinal photography is a standard method for recording retinal diseases for subsequent analysis and diagnosis. However, the currently used white light or red-free retinal imaging does not necessarily provide the best possible visibility of different types of retinal lesions, important when developing diagnostic tools for handheld devices, such as smartphones. Using specifically designed illumination, the visibility and contrast of retinal lesions could be improved. In this study, spectrally optimal illuminations for diabetic retinopathy lesion visualization are implemented using a spectrally tunable light source based on digital micromirror device. The applicability of this method was tested in vivo by taking retinal monochrome images from the eyes of five diabetic volunteers and two non-diabetic control subjects. For comparison to existing methods, we evaluated the contrast of retinal images taken with our method and red-free illumination. The preliminary results show that the use of optimal illuminations improved the contrast of diabetic lesions in retinal images by 30-70%, compared to the traditional red-free illumination imaging.

STRUCTURAL ASSESSMENT OF HYPERAUTOFLUORESCENT RING IN PATIENTS WITH RETINITIS PIGMENTOSA

PubMed Central

LIMA, LUIZ H.; CELLA, WENER; GREENSTEIN, VIVIENNE C.; WANG, NAN-KAI; BUSUIOC, MIHAI; THEODORE SMITH, R.; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.

2009-01-01

Purpose To analyze the retinal structure underlying the hyperautofluorescent ring visible on fundus autofluorescence in patients with retinitis pigmentosa. Methods Twenty-four eyes of 13 patients with retinitis pigmentosa, aged 13 years to 67 years, were studied. The integrity of the photoreceptor cilia, also known as the inner/outer segment junction of the photoreceptors, the outer nuclear layer, and retinal pigment epithelium, was evaluated outside, across, and inside the ring with spectral-domain optical coherence tomography (OCT). Results Inside the foveal area, fundus autofluorescence did not detect abnormalities. Outside the ring, fundus autofluorescence revealed hypoautofluorescence compatible with the photoreceptor/retinal pigment epithelium degeneration. Spectral-domain OCT inside the ring, in the area of normal foveal fundus autofluorescence, revealed an intact retinal structure in all eyes and total retinal thickness values that were within normal limits. Across the ring, inner/outer segment junction disruption was observed and the outer nuclear layer was decreased in thickness in a centrifugal direction in all eyes. Outside the hyperautofluorescent ring, the inner/outer segment junction and the outer nuclear layer appeared to be absent and there were signs of retinal pigment epithelium degeneration. Conclusion Disruption of the inner/outer segment junction and a decrease in outer retinal thickness were found across the central hyperautofluorescent ring seen in retinitis pigmentosa. Outer segment phagocytosis by retinal pigment epithelium is necessary for the formation of an hyperautofluorescent ring. PMID:19584660

Retinal complications after aqueous shunt surgical procedures for glaucoma.

PubMed

Law, S K; Kalenak, J W; Connor, T B; Pulido, J S; Han, D P; Mieler, W F

1996-12-01

To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.

The Edge Detectors Suitable for Retinal OCT Image Segmentation

PubMed Central

Yang, Jing; Gao, Qian; Zhou, Sheng

2017-01-01

Retinal layer thickness measurement offers important information for reliable diagnosis of retinal diseases and for the evaluation of disease development and medical treatment responses. This task critically depends on the accurate edge detection of the retinal layers in OCT images. Here, we intended to search for the most suitable edge detectors for the retinal OCT image segmentation task. The three most promising edge detection algorithms were identified in the related literature: Canny edge detector, the two-pass method, and the EdgeFlow technique. The quantitative evaluation results show that the two-pass method outperforms consistently the Canny detector and the EdgeFlow technique in delineating the retinal layer boundaries in the OCT images. In addition, the mean localization deviation metrics show that the two-pass method caused the smallest edge shifting problem. These findings suggest that the two-pass method is the best among the three algorithms for detecting retinal layer boundaries. The overall better performance of Canny and two-pass methods over EdgeFlow technique implies that the OCT images contain more intensity gradient information than texture changes along the retinal layer boundaries. The results will guide our future efforts in the quantitative analysis of retinal OCT images for the effective use of OCT technologies in the field of ophthalmology. PMID:29065594

Stem cell therapy for retinal diseases

PubMed Central

Garcia, José Mauricio; Mendonça, Luisa; Brant, Rodrigo; Abud, Murilo; Regatieri, Caio; Diniz, Bruno

2015-01-01

In this review, we discuss about current knowledge about stem cell (SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt’s dystrophy, and patients with geographic atrophy, providing good outcomes. This study’s intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients’ vision, and, finally, approaching future directions and challenges for the treatment of several conditions. PMID:25621115

Ultra-Widefield Steering-Based SD-OCT Imaging of the Retinal Periphery

PubMed Central

Choudhry, Netan; Golding, John; Manry, Matthew W.; Rao, Rajesh C.

2016-01-01

Objective To describe the spectral-domain optical coherence tomography (SD-OCT) features of peripheral retinal findings using an ultra-widefield (UWF) steering technique to image the retinal periphery. Design Observational study. Participants 68 patients (68 eyes) with 19 peripheral retinal features. Main Outcome Measures SD-OCT-based structural features. Methods Nineteen peripheral retinal features including: vortex vein, congenital hypertrophy of the retinal pigment epithelium (CHRPE), pars plana, ora serrata pearl, typical cystoid degeneration (TCD), cystic retinal tuft, meridional fold, lattice and cobblestone degeneration, retinal hole, retinal tear, rhegmatogenous retinal detachment (RRD), typical degenerative senile retinoschisis, peripheral laser coagulation scars, ora tooth, cryopexy scars (retinal tear and treated retinoblastoma scar), bone spicules, white without pressure, and peripheral drusen were identified by peripheral clinical examination. Near infrared (NIR) scanning laser ophthalmoscopy (SLO) images and SD-OCT of these entities were registered to UWF color photographs. Results SD-OCT resolved structural features of all peripheral findings. Dilated hyporeflective tubular structures within the choroid were observed in the vortex vein. Loss of retinal lamination, neural retinal attenuation, RPE loss or hypertrophy were seen in several entities including CHRPE, ora serrata pearl, TCD, cystic retinal tuft, meridional fold, lattice and cobblestone degenerations. Hyporeflective intraretinal spaces, indicating cystoid or schitic fluid, were seen in ora serrata pearl, ora tooth, TCD, cystic retinal tuft, meridional fold, retinal hole, and typical degenerative senile retinoschisis. The vitreoretinal interface, which often consisted of lamellae-like structures of the condensed cortical vitreous near or adherent to the neural retina, appeared clearly in most peripheral findings, confirming its association with many low-risk and vision-threatening pathologies

Nitric oxide regulates retinal vascular tone in humans.

PubMed

Dorner, Guido T; Garhofer, Gerhard; Kiss, Barbara; Polska, Elzbieta; Polak, Kaija; Riva, Charles E; Schmetterer, Leopold

2003-08-01

The purpose of the present study was to investigate the contribution of basal nitric oxide (NO) on retinal vascular tone in humans. In addition, we set out to elucidate the role of NO in flicker-induced retinal vasodilation in humans. Twelve healthy young subjects were studied in a three-way crossover design. Subjects received an intravenous infusion of either placebo or NG-monomethyl-L-arginine (L-NMMA; 3 or 6 mg/kg over 5 min), an inhibitor of NO synthase. Thereafter, diffuse luminance flicker was consecutively performed for 16, 32, and 64 s at a frequency of 8 Hz. The effect of L-NMMA on retinal arterial and venous diameter was assessed under resting conditions and during the hyperemic flicker response. Retinal vessel diameter was measured with a Zeiss retinal vessel analyzer. L-NMMA significantly reduced arterial diameter (3 mg/kg: -2%; 6 mg/kg: -4%, P < 0.001) and venous diameter (3 mg/kg: -5%; 6 mg/kg: -8%, P < 0.001). After placebo infusion, flicker induced a significant increase in retinal vessel diameter (P < 0.001). At a flicker duration of 64 s, arterial diameter increased by 4% and venous diameter increased by 3%. L-NMMA did not abolish these hyperemic responses but blunted venous vasodilation (P = 0.017) and arterial vasodilation (P = 0.02) in response to flicker stimulation. Our data indicate that NO contributes to basal retinal vascular tone in humans. In addition, NO appears to play a role in flicker-induced vasodilation of the human retinal vasculature.

Retinal image quality during accommodation.

PubMed

López-Gil, Norberto; Martin, Jesson; Liu, Tao; Bradley, Arthur; Díaz-Muñoz, David; Thibos, Larry N

2013-07-01

We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Subjects viewed a monochromatic (552 nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye's higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced visual function may be a useful

Extracellular Matrix Degradation and Remodeling in Development and Disease

PubMed Central

Lu, Pengfei; Takai, Ken; Weaver, Valerie M.; Werb, Zena

2011-01-01

The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine. PMID:21917992

Bone remodelling: its local regulation and the emergence of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2008-10-01

Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.

Frontiers in growth and remodeling

PubMed Central

Menzel, Andreas; Kuhl, Ellen

2012-01-01

Unlike common engineering materials, living matter can autonomously respond to environmental changes. Living structures can grow stronger, weaker, larger, or smaller within months, weeks, or days as a result of a continuous microstructural turnover and renewal. Hard tissues can adapt by increasing their density and grow strong. Soft tissues can adapt by increasing their volume and grow large. For more than three decades, the mechanics community has actively contributed to understand the phenomena of growth and remodeling from a mechanistic point of view. However, to date, there is no single, unified characterization of growth, which is equally accepted by all scientists in the field. Here we shed light on the continuum modeling of growth and remodeling of living matter, and give a comprehensive overview of historical developments and trends. We provide a state-of-the-art review of current research highlights, and discuss challenges and potential future directions. Using the example of volumetric growth, we illustrate how we can establish and utilize growth theories to characterize the functional adaptation of soft living matter. We anticipate this review to be the starting point for critical discussions and future research in growth and remodeling, with a potential impact on life science and medicine. PMID:22919118

The influence of retinal eye diseases on painting.

PubMed

Ivanišević, Petar; Ivanišević, Milan

2015-03-01

In this work the possible influences of some retinal eye problems on paintings of several famous artists are considered. The change of painting styles and artistic expression in different periods and ages in a group of world-wide well-known painters are described and correlated with known or suspected retinal diseases. Some of them largely became recognizable because of that. Contemplations are offered about the effects of retinal diseases in the works of Degas, Munch, Cézanne, O'Keeffe, Constable and Goya. Retinal eye diseases have a significant impact on the work of selected famous painters.

Strategy for the management of uncomplicated retinal detachments: the European vitreo-retinal society retinal detachment study report 1.

PubMed

Adelman, Ron A; Parnes, Aaron J; Ducournau, Didier

2013-09-01

To study success and failure in the treatment of uncomplicated rhegmatogenous retinal detachments (RRDs). Nonrandomized, multicenter retrospective study. One hundred seventy-six surgeons from 48 countries spanning 5 continents provided information on the primary procedures for 7678 cases of RRDs including 4179 patients with uncomplicated RRDs. Reported data included specific clinical findings, the method of repair, and the outcome after intervention. Final failure of retinal detachment repair (level 1 failure rate), remaining silicone oil at the study's conclusion (level 2 failure rate), and need for additional procedures to repair the detachment (level 3 failure rate). Four thousand one hundred seventy-nine uncomplicated cases of RRD were included. Combining phakic, pseudophakic, and aphakic groups, those treated with scleral buckle alone (n = 1341) had a significantly lower final failure rate than those treated with vitrectomy, with or without a supplemental buckle (n = 2723; P = 0.04). In phakic patients, final failure rate was lower in the scleral buckle group compared with those who had vitrectomy, with or without a supplemental buckle (P = 0.028). In pseudophakic patients, the failure rate of the initial procedure was lower in the vitrectomy group compared with the scleral buckle group (P = 3×10(-8)). There was no statistically significant difference in failure rate between segmental (n = 721) and encircling (n = 351) buckles (P = 0.5). Those who underwent vitrectomy with a supplemental scleral buckle (n = 488) had an increased failure rate compared with those who underwent vitrectomy alone (n = 2235; P = 0.048). Pneumatic retinopexy was found to be comparable with scleral buckle when a retinal hole was present (P = 0.65), but not in cases with a flap tear (P = 0.034). In the treatment of uncomplicated phakic retinal detachments, repair using scleral buckle may be a good option. There was no significant difference between segmental versus 360-degree buckle

Characterizing the spectrum of right ventricular remodelling in response to chronic training.

PubMed

Sitges, Marta; Merino, Beatriz; Butakoff, Constatine; de la Garza, Maria Sanz; Paré, Carles; Montserrat, Silvia; Vidal, Barbara; Azqueta, Manel; Sarquella, Georgia; Gutierrez, Josep Antoni; Canal, Ramon; Brugada, Josep; Bijnens, Bart H

2017-03-01

The significance and spectrum of reduced right ventricular (RV) deformation, reported in endurance athletes, is unclear. To comprehensively analyze the cardiac performance at rest of athletes, especially focusing on integrating RV size and deformation to unravel the underlying triggers of this ventricular remodelling. Hundred professional male athletes and 50 sedentary healthy males of similar age were prospectively studied. Conventional echocardiographic parameters of all four chambers were obtained, as well as 2D echo-derived strain (2DSE) in the left (LV) and in the RV free wall with separate additional analysis of the RV basal and apical segments. Left and right-sided dimensions were larger in athletes than in controls, but with a disproportionate RA enlargement. RV global strain was lower in sportsmen (-26.8 ± 2.8% vs -28.5 ± 3.4%, p < 0.001) due to a decrease in the basal segment (-22.8 ± 3.5% vs -25.8 ± 4.0%, p < 0.001) resulting in a marked gradient of deformation from the RV inlet towards the apex. By integrating size, deformation and stroke volume, we observed that the LV working conditions were similar in all sportsmen while a wider variability existed in the RV. Cardiac remodelling in athletes is more pronounced in the right heart cavities with specific regional differences within the right ventricle, but with a wide variability among individuals. The large inter-individual differences, as well as its acute and chronic relevance warrant further investigation.

Flexible trigger menu implementation on the Global Trigger for the CMS Level-1 trigger upgrade

NASA Astrophysics Data System (ADS)

MATSUSHITA, Takashi; CMS Collaboration

2017-10-01

The CMS experiment at the Large Hadron Collider (LHC) has continued to explore physics at the high-energy frontier in 2016. The integrated luminosity delivered by the LHC in 2016 was 41 fb-1 with a peak luminosity of 1.5 × 1034 cm-2s-1 and peak mean pile-up of about 50, all exceeding the initial estimations for 2016. The CMS experiment has upgraded its hardware-based Level-1 trigger system to maintain its performance for new physics searches and precision measurements at high luminosities. The Global Trigger is the final step of the CMS Level-1 trigger and implements a trigger menu, a set of selection requirements applied to the final list of objects from calorimeter and muon triggers, for reducing the 40 MHz collision rate to 100 kHz. The Global Trigger has been upgraded with state-of-the-art FPGA processors on Advanced Mezzanine Cards with optical links running at 10 GHz in a MicroTCA crate. The powerful processing resources of the upgraded system enable implementation of more algorithms at a time than previously possible, allowing CMS to be more flexible in how it handles the available trigger bandwidth. Algorithms for a trigger menu, including topological requirements on multi-objects, can be realised in the Global Trigger using the newly developed trigger menu specification grammar. Analysis-like trigger algorithms can be represented in an intuitive manner and the algorithms are translated to corresponding VHDL code blocks to build a firmware. The grammar can be extended in future as the needs arise. The experience of implementing trigger menus on the upgraded Global Trigger system will be presented.

Intraocular retinal prosthesis.

PubMed Central

Humayun, M S

2001-01-01

PURPOSE: An electronic implant that can bypass the damaged photoreceptors and electrically stimulate the remaining retinal neurons to restore useful vision has been proposed. A number of key questions remain to make this approach feasible. The goal of this thesis is to address the following 2 specific null hypotheses: (1) Stimulus parameters make no difference in the electrically elicited retinal responses. (2) Just as we have millions of photoreceptors, so it will take a device that can generate millions of pixels/light points to create useful vision. METHODS: For electrophysiologic experiments, 2 different setups were used. In the first setup, charge-balanced pulses were delivered to the retinal surface via electrodes inserted through an open sky approach in normal or blind retinal degenerate (rd) mice. In the second setup, the rabbit retina was removed under red light conditions from an enucleated eye and then maintained in a chamber while being superfused with oxygenated, heated Ames media. In both setups, stimulating electrodes and recording electrodes were positioned on the retinal surface to evaluate the effect of varying stimulation parameters on the orthodromic retinal responses (i.e., recording electrode placed between stimulating electrodes and optic nerve head). For psychophysical experiments, visual images were divided into pixels of light that could be projected in a pattern on the retina in up to 8 sighted volunteers. Subjects were asked to perform various tasks ranging from reading and face recognition to various activities of daily living. RESULTS: Electrophysiologic experiments: In a normal mouse, a single cycle of a 1-kHz sine wave was significantly more efficient than a 1-kHz square wave (P < .05), but no such difference was noted in either of the 8- or 16-week-old rd mouse groups (8-week-old, P = .426; 16-week-old, P = .078). Charge threshold was significantly higher in 16-week-old rd mouse versus both 8-week-old rd and normal mouse for every

RI in central retinal artery as assessed by CDI does not correspond to retinal vascular resistance.

PubMed

Polska, E; Kircher, K; Ehrlich, P; Vecsei, P V; Schmetterer, L

2001-04-01

The aim of the present study was to investigate the association between ultrasound Doppler measurements of resistive index (RI) in the central retinal artery and retinal vascular resistance (R) assessed with laser Doppler velocimetry, vessel size measurement, and calculation of ocular perfusion pressure (PP) in healthy subjects. An increase in vascular resistance was induced by inhalation of 100% O(2). During hyperoxia no significant changes in PP were observed. Mean flow velocity in main retinal veins was reduced by -27.5 +/- 2.0%. The average decrease in diameter was -11.5 +/- 1.0%. R, which was calculated as the ratio of PP to flow rate, increased by 97.6 +/- 7.7%. RI increased as well, but the effect was much smaller (6.6 +/- 2.2%). In addition, a negative correlation was found between baseline values of R and RI (r = -0.83). During hyperoxia R and RI were not associated. In conclusion, our data indicate that RI as assessed with color Doppler imaging in the central retinal artery is not an adequate measure of R.

Visible-light OCT to quantify retinal oxygen metabolism (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhang, Hao F.; Yi, Ji; Chen, Siyu; Liu, Wenzhong; Soetikno, Brian T.

2016-03-01

We explored, both numerically and experimentally, whether OCT can be a good candidate to accurately measure retinal oxygen metabolism. We first used statistical methods to numerically simulate photon transport in the retina to mimic OCT working under different spectral ranges. Then we analyze accuracy of OCT oximetry subject to parameter variations such as vessel size, pigmentation, and oxygenation. We further developed an experimental OCT system based on the spectral range identified by our simulation work. We applied the newly developed OCT to measure both retinal hemoglobin oxygen saturation (sO2) and retinal retinal flow. After obtaining the retinal sO2 and blood velocity, we further measured retinal vessel diameter and calculated the retinal oxygen metabolism rate (MRO2). To test the capability of our OCT, we imaged wild-type Long-Evans rats ventilated with both normal air and air mixtures with various oxygen concentrations. Our simulation suggested that OCT working within visible spectral range is able to provide accurate measurement of retinal MRO2 using inverse Fourier transform spectral reconstruction. We called this newly developed technology vis-OCT, and showed that vis-OCT was able to measure the sO2 value in every single major retinal vessel around the optical disk as well as in micro retinal vessels. When breathing normal air, the averaged sO2 in arterial and venous blood in Long-Evans rats was measured to be 95% and 72%, respectively. When we challenge the rats using air mixtures with different oxygen concentrations, vis-OCT measurement followed analytical models of retinal oxygen diffusion and pulse oximeter well.

Age-Related Alterations in the Retinal Microvasculature, Microcirculation, and Microstructure.

PubMed

Wei, Yantao; Jiang, Hong; Shi, Yingying; Qu, Dongyi; Gregori, Giovanni; Zheng, Fang; Rundek, Tatjana; Wang, Jianhua

2017-07-01

To characterize age-related alterations in the retinal microcirculation, microvascular network, and microstructure in healthy subjects. Seventy-four healthy subjects aged from 18 to 82 years were recruited and divided into four age groups (G1 with age <35 years, G2 with age 35 ∼ 49 years, G3 with age 50 ∼ 64 years, and G4 with age ≥65 years). Custom ultra-high resolution optical coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the macula. OCT angiography (OCTA) was used to image the retinal microvascular network. The retinal blood flow velocity (BFV) was measured using a Retinal Function Imager (RFI). Compared to G1, G2 had significant thinning of the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05). Age was negatively related to retinal vessel densities, the inner retinal layers, and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR (P < 0.05). During aging, decreases in retinal vessel density, inner retinal layer thickness, and venular BFV were evident and impacted each other as observed by simultaneous changes in multiple retinal components.

Age-Related Alterations in the Retinal Microvasculature, Microcirculation, and Microstructure

PubMed Central

Wei, Yantao; Jiang, Hong; Shi, Yingying; Qu, Dongyi; Gregori, Giovanni; Zheng, Fang; Rundek, Tatjana; Wang, Jianhua

2017-01-01

Purpose To characterize age-related alterations in the retinal microcirculation, microvascular network, and microstructure in healthy subjects. Methods Seventy-four healthy subjects aged from 18 to 82 years were recruited and divided into four age groups (G1 with age <35 years, G2 with age 35 ∼ 49 years, G3 with age 50 ∼ 64 years, and G4 with age ≥65 years). Custom ultra-high resolution optical coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the macula. OCT angiography (OCTA) was used to image the retinal microvascular network. The retinal blood flow velocity (BFV) was measured using a Retinal Function Imager (RFI). Results Compared to G1, G2 had significant thinning of the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05). Age was negatively related to retinal vessel densities, the inner retinal layers, and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR (P < 0.05). Conclusions During aging, decreases in retinal vessel density, inner retinal layer thickness, and venular BFV were evident and impacted each other as observed by simultaneous changes in multiple retinal components. PMID:28744554

Retinal and visual system: occupational and environmental toxicology.

PubMed

Fox, Donald A

2015-01-01

Occupational chemical exposure often results in sensory systems alterations that occur without other clinical signs or symptoms. Approximately 3000 chemicals are toxic to the retina and central visual system. Their dysfunction can have immediate, long-term, and delayed effects on mental health, physical health, and performance and lead to increased occupational injuries. The aims of this chapter are fourfold. First, provide references on retinal/visual system structure, function, and assessment techniques. Second, discuss the retinal features that make it especially vulnerable to toxic chemicals. Third, review the clinical and corresponding experimental data regarding retinal/visual system deficits produced by occupational toxicants: organic solvents (carbon disulfide, trichloroethylene, tetrachloroethylene, styrene, toluene, and mixtures) and metals (inorganic lead, methyl mercury, and mercury vapor). Fourth, discuss occupational and environmental toxicants as risk factors for late-onset retinal diseases and degeneration. Overall, the toxicants altered color vision, rod- and/or cone-mediated electroretinograms, visual fields, spatial contrast sensitivity, and/or retinal thickness. The findings elucidate the importance of conducting multimodal noninvasive clinical, electrophysiologic, imaging and vision testing to monitor toxicant-exposed workers for possible retinal/visual system alterations. Finally, since the retina is a window into the brain, an increased awareness and understanding of retinal/visual system dysfunction should provide additional insight into acquired neurodegenerative disorders. © 2015 Elsevier B.V. All rights reserved.

LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

PubMed

Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A

2016-12-01

To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms. Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.

Arrestin gene mutations in autosomal recessive retinitis pigmentosa.

PubMed

Nakazawa, M; Wada, Y; Tamai, M

1998-04-01

To assess the clinical and molecular genetic studies of patients with autosomal recessive retinitis pigmentosa associated with a mutation in the arrestin gene. Results of molecular genetic screening and case reports with DNA analysis and clinical features. University medical center. One hundred twenty anamnestically unrelated patients with autosomal recessive retinitis pigmentosa. DNA analysis was performed by single strand conformation polymorphism followed by nucleotide sequencing to search for a mutation in exon 11 of the arrestin gene. Clinical features were characterized by visual acuity slitlamp biomicroscopy, fundus examinations, fluorescein angiography, kinetic visual field testing, and electroretinography. We identified 3 unrelated patients with retinitis pigmentosa associated with a homozygous 1-base-pair deletion mutation in codon 309 of the arrestin gene designated as 1147delA. All 3 patients showed pigmentary retinal degeneration in the midperipheral area with or without macular involvement. Patient 1 had a sibling with Oguchi disease associated with the same mutation. Patient 2 demonstrated pigmentary retinal degeneration associated with a golden-yellow reflex in the peripheral fundus. Patients 1 and 3 showed features of retinitis pigmentosa without the golden-yellow fundus reflex. Although the arrestin 1147delA has been known as a frequent cause of Oguchi disease, this mutation also may be related to the pathogenesis of autosomal recessive retinitis pigmentosa. This phenomenon may provide evidence of variable expressivity of the mutation in the arrestin gene.

[Bone remodeling and modeling/mini-modeling.

PubMed

Hasegawa, Tomoka; Amizuka, Norio

Modeling, adapting structures to loading by changing bone size and shapes, often takes place in bone of the fetal and developmental stages, while bone remodeling-replacement of old bone into new bone-is predominant in the adult stage. Modeling can be divided into macro-modeling(macroscopic modeling)and mini-modeling(microscopic modeling). In the cellular process of mini-modeling, unlike bone remodeling, bone lining cells, i.e., resting flattened osteoblasts covering bone surfaces will become active form of osteoblasts, and then, deposit new bone onto the old bone without mediating osteoclastic bone resorption. Among the drugs for osteoporotic treatment, eldecalcitol(a vitamin D3 analog)and teriparatide(human PTH[1-34])could show mini-modeling based bone formation. Histologically, mature, active form of osteoblasts are localized on the new bone induced by mini-modeling, however, only a few cell layer of preosteoblasts are formed over the newly-formed bone, and accordingly, few osteoclasts are present in the region of mini-modeling. In this review, histological characteristics of bone remodeling and modeling including mini-modeling will be introduced.

[Cytomegalovirus retinitis in HIV negative patients - retrospective study].

PubMed

Beňová, A; Brichová, M; Svozílková, P; Kousal, B; Jeníčková, D; Heissigerová, J; Ríhová, E

2013-12-01

To evaluate own experience with the diagnosis and treatment of cytomegalovirus (CMV) retinitis in HIV negative patients with immunodeficiency. Retrospective study and case reports. In the Centre for diagnosis and treatment of Uveitis 1869 patients with uveitis we have examined from June 2003 to June 2012. CMV retinitis was diagnosed in 7 patients (1 woman and 6 men) according to the typical clinical findings and history of immunodeficiency. In 2 atypical findings was the diagnosis confirmed by determination of DNA pathogen in vitreous sample (a patient with non-Hodgkin lymphoma) or by positive serology (CMV in leukocytes - indolent form of CMV retinitis in a patient with systemic lupus erythematosus). In 8 cases we found fulminant form, in 1 case indolent form of CMV retinitis. The average age of patients was 39,1 years (18-51 years old), ratio of men to women 6 : 3. In 6 of 9 cases we noticed bilateral retinitis. The average period of observation in our study was 15,8 months (1-48 months). Five of our patients underwent bone marrow transplantation, 2 patients were treated with systemic immunosuppressive drugs (colitis ulcerosa, systemic lupus erythematosus) and 2 patients had chemotherapy for lymphoma. The initiation or modification of treatment (gancyklovir p.o./i.v., foscarnet i.v.) was consulted and coordinated with others specialists. After initiation of treatment we followed-up 7 patients. In 4 eyes of 3 patients (31 %) the improvement of visual acuity was documented, in 5 eyes of 5 patients (38 %) the visual acuity was stabilized. The worsening of vision in 4 eyes of 3 patients (31 %) was caused by complications without any connection to virostatic therapy. All of our patients, who underwent bone marrow transplantation, died within 12 months since the diagnosis of CMV retinitis was determined. The diagnosis of CMV retinitis only in 9 cases (0,48% of all uveitic patients) confirms the rare occurrence of this retinitis. The important tool to the diagnosis of

Neuroprotective therapy for argon-laser-induced retinal injury

NASA Astrophysics Data System (ADS)

Belkin, Michael; Rosner, Mordechai; Solberg, Yoram; Turetz, Yosef

1999-06-01

Laser photocoagulation treatment of the central retina is often complicated by an immediate side effect of visual impairment, caused by the unavoidable laser-induced destruction of the normal tissue lying adjacent to the lesion and not affected directly by the laser beam. Furthermore, accidental laser injuries are at present untreatable. A neuroprotective therapy for salvaging the normal tissue might enhance the benefit obtained from treatment and allow safe perifoveal photocoagulation. We have developed a rat model for studying the efficacy of putative neuroprotective compounds in ameliorating laser-induced retinal damage. Four compounds were evaluated: the corticosteroid methylprednisolone, the glutamate-receptor blocker MK-801, the anti-oxidant enzyme superoxide dismutase, and the calcim-overload antagonist flunarizine. The study was carried out in two steps: in the first, the histopathological development of retinal laser injuries was studied. Argon laser lesions were inflicted in the retinas of 18 pigmented rats. The animals were sacrificed after 3, 20 or 60 days and their retinal lesions were evaluated under the light microscope. The laser injury mainly involved the outer layers of the retina, where it destroyed significant numbers of photoreceptor cells. Over time, evidence of two major histopathological processes was observed: traction of adjacent nomral retinal cells into the central area of the lesion forming an internal retinal bulging, and a retinal pigmented epithelial proliferative reaction associated with subretinal neovascularization and invations of the retinal lesion site by phagocytes. The neuroprotective effects of each of the four compounds were verified in a second step of the study. For each drug tested, 12 rats were irradiated wtih argon laser inflictions: six of them received the tested agent while the other six were treated with the corresponding vehicle. Twenty days after laser expsoure, the rats were sacrificed and their lesions were

Comparison of low-cost handheld retinal camera and traditional table top retinal camera in the detection of retinal features indicating a risk of cardiovascular disease

NASA Astrophysics Data System (ADS)

Joshi, V.; Wigdahl, J.; Nemeth, S.; Zamora, G.; Ebrahim, E.; Soliz, P.

2018-02-01

Retinal abnormalities associated with hypertensive retinopathy are useful in assessing the risk of cardiovascular disease, heart failure, and stroke. Assessing these risks as part of primary care can lead to a decrease in the incidence of cardiovascular disease-related deaths. Primary care is a resource limited setting where low cost retinal cameras may bring needed help without compromising care. We compared a low-cost handheld retinal camera to a traditional table top retinal camera on their optical characteristics and performance to detect hypertensive retinopathy. A retrospective dataset of N=40 subjects (28 with hypertensive retinopathy, 12 controls) was used from a clinical study conducted at a primary care clinic in Texas. Non-mydriatic retinal fundus images were acquired using a Pictor Plus hand held camera (Volk Optical Inc.) and a Canon CR1-Mark II tabletop camera (Canon USA) during the same encounter. The images from each camera were graded by a licensed optometrist according to the universally accepted Keith-Wagener-Barker Hypertensive Retinopathy Classification System, three weeks apart to minimize memory bias. The sensitivity of the hand-held camera to detect any level of hypertensive retinopathy was 86% compared to the Canon. Insufficient photographer's skills produced 70% of the false negative cases. The other 30% were due to the handheld camera's insufficient spatial resolution to resolve the vascular changes such as minor A/V nicking and copper wiring, but these were associated with non-referable disease. Physician evaluation of the performance of the handheld camera indicates it is sufficient to provide high risk patients with adequate follow up and management.

Thrombospondin-2 Expression During Retinal Vascular Development and Neovascularization.

PubMed

Fei, Ping; Palenski, Tammy L; Wang, Shoujian; Gurel, Zafer; Hankenson, Kurt D; Sorenson, Christine M; Sheibani, Nader

2015-09-01

To determine thrombospondin-2 (TSP2) expression and its impact on postnatal retinal vascular development and retinal neovascularization. The TSP2-deficient (TSP2(-/-)) mice and a line of TSP2 reporter mice were used to assess the expression of TSP2 during postnatal retinal vascular development and neovascularization. The postnatal retinal vascularization was evaluated using immunostaining of wholemount retinas prepared at different postnatal days by collagen IV staining and/or TSP2 promoter driven green fluorescent protein (GFP) expression. The organization of astrocytes was evaluated by glial fibrillary acidic protein (GFAP) staining. Retinal vascular densities were determined using trypsin digestion preparation of wholemount retinas at 3- and 6-weeks of age. Retinal neovascularization was assessed during the oxygen-induced ischemic retinopathy (OIR). Choroidal neovascularization (CNV) was assessed using laser-induced CNV. Using the TSP2-GFP reporter mice, we observed significant expression of TSP2 mRNA in retinas of postnatal day 5 (P5) mice, which increased by P7 and remained high up to P42. Similar results were observed in retinal wholemount preparations, and western blotting for GFP with the highest level of GFP was observed at P21. In contrast to high level of mRNA at P42, the GFP fluorescence or protein level was dramatically downregulated. The primary retinal vasculature developed at a faster rate in TSP2(-/-) mice compared with TSP2(+/+) mice up to P5. However, the developing retinal vasculature in TSP2(+/+) mice caught up with that of TSP2(-/-) mice after P7. No significant differences in retinal vascular density were observed at 3- or 6-weeks of age. TSP2(-/-) mice also exhibited a similar sensitivity to the hyperoxia-mediated vessel obliteration and similar level of neovascularization during OIR as TSP2(+/+) mice. Lack of TSP2 expression minimally affected laser-induced CNV compared with TSP2(+/+) mice. Lack of TSP2 expression was associated with

Cytomegalovirus retinitis in patients with AIDS after initiating antiretroviral therapy

PubMed Central

Jabs, Douglas A.; Van Natta, Mark L.; Holland, Gary N.; Danis, Ronald

2016-01-01

Purpose To evaluate the rates of new-onset cytomegalovirus (CMV) retinitis and worsening existing CMV retinitis in patients with AIDS after initiating combination antiretroviral therapy (cART) and the role of an immune recovery inflammatory syndrome (IRIS). Design Cohort study Methods Immune recovery was defined as an increase in CD4+ T cells to ≥100 cells/μL; rates of new-onset CMV retinitis and of worsening of CMV retinitis (either increasing border activity or retinitis progression) were compared between those with and without immune recovery. Results Among patients without CMV retinitis, 1 of 75 patients with immune recovery developed CMV retinitis in the first 6 months after initiating cART vs. 1 of 31 without immune recovery (P=0.14). Among patients with CMV retinitis, the rates of retinitis progression and increasing retinitis border activity among patients during the first 6 months after initiating cART in those with immune recovery were 0.11/PY (95% confidence interval [CI] 0, 0.62) and 0.11/PY (95% CI 0, 0.62), respectively, vs. 0.67/PY (95% CI 0.22, 1.56) and 0.40/PY (95% CI 0.08, 1.17), respectively, for those without immune recovery (P=0.11 and 0.47). Conclusions Among persons with AIDS who experience immune recovery, there was neither an increased rate of new-onset CMV retinitis nor worsening of existing CMV retinitis in the first 6 months after initiating cART vs. those without immune recovery. These data are consistent with the known 3–6 month lag in recovery of specific immunity to CMV after initiating cART and suggest that “immune recovery retinitis”, a proposed IRIS phenomenon, is rare. PMID:27984023

Human bone marrow mesenchymal stem cells for retinal vascular injury.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Jonas, Jost B; Xu, Liang; Zhang, Wei

2017-09-01

To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count. In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36). Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley

Automated retinal fovea type distinction in spectral-domain optical coherence tomography of retinal vein occlusion

NASA Astrophysics Data System (ADS)

Wu, Jing; Waldstein, Sebastian M.; Gerendas, Bianca S.; Langs, Georg; Simader, Christian; Schmidt-Erfurth, Ursula

2015-03-01

Spectral-domain Optical Coherence Tomography (SD-OCT) is a non-invasive modality for acquiring high- resolution, three-dimensional (3D) cross-sectional volumetric images of the retina and the subretinal layers. SD-OCT also allows the detailed imaging of retinal pathology, aiding clinicians in the diagnosis of sight degrading diseases such as age-related macular degeneration (AMD), glaucoma and retinal vein occlusion (RVO). Disease diagnosis, assessment, and treatment will require a patient to undergo multiple OCT scans, possibly using multiple scanners, to accurately and precisely gauge disease activity, progression and treatment success. However, cross-vendor imaging and patient movement may result in poor scan spatial correlation potentially leading to incorrect diagnosis or treatment analysis. The retinal fovea is the location of the highest visual acuity and is present in all patients, thus it is critical to vision and highly suitable for use as a primary landmark for cross-vendor/cross-patient registration for precise comparison of disease states. However, the location of the fovea in diseased eyes is extremely challenging to locate due to varying appearance and the presence of retinal layer destroying pathology. Thus categorising and detecting the fovea type is an important prior stage to automatically computing the fovea position. Presented here is an automated cross-vendor method for fovea distinction in 3D SD-OCT scans of patients suffering from RVO, categorising scans into three distinct types. OCT scans are preprocessed by motion correction and noise filing followed by segmentation using a kernel graph-cut approach. A statistically derived mask is applied to the resulting scan creating an ROI around the probable fovea location from which the uppermost retinal surface is delineated. For a normal appearance retina, minimisation to zero thickness is computed using the top two retinal surfaces. 3D local minima detection and layer thickness analysis are used

Combined branch retinal vein and artery occlusion in toxoplasmosis.

PubMed

Aggio, Fabio Bom; Novelli, Fernando José de; Rosa, Evandro Luis; Nobrega, Mário Junqueira

2016-01-01

A 22-year-old man complained of low visual acuity and pain in his left eye for five days. His ophthalmological examination revealed 2+ anterior chamber reaction and a white, poorly defined retinal lesion at the proximal portion of the inferotemporal vascular arcade. There were retinal hemorrhages in the inferotemporal region extending to the retinal periphery. In addition, venous dilation, increased tortuosity, and ischemic retinal whitening along the inferotemporal vascular arcade were also observed. A proper systemic work-up was performed, and the patient was diagnosed with ocular toxoplasmosis. He was treated with an anti-toxoplasma medication, and his condition slowly improved. Inferior macular inner and middle retinal atrophy could be observed on optical coherence tomography as a sequela of ischemic injury. To our knowledge, this is the first report of combined retinal branch vein and artery occlusion in toxoplasmosis resulting in a striking and unusual macular appearance.

Active retinitis in an infant with postnatally acquired cytomegalovirus infection.

PubMed

Piersigilli, F; Catena, G; De Gasperis, M R; Lozzi, S; Auriti, C

2012-07-01

Congenital cytomegalovirus (CMV) is frequently associated with active retinitis. In contrast, in the immunocompetent neonate with postnatally acquired CMV infection retinitis is rarely present and usually does not progress. We describe the case of an infant with postnatal CMV infection and active retinitis diagnosed at 20 days of life. Owing to the rapid progression of the retinitis, therapy with intravenous ganciclovir was performed, with prompt regression of the retinitis. Therapy was then continued with oral valganciclovir for one further week. Although very unusual, CMV retinitis has to be taken into consideration in neonates with early postnatally acquired CMV infection, as an early diagnosis and treatment may be crucial to avoid visual impairment.

Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

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

Sharma, Gulshan B., E-mail: gbsharma@ucalgary.ca; University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213; University of Calgary, Schulich School of Engineering, Department of Mechanical and Manufacturing Engineering, Calgary, Alberta T2N 1N4

Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respondmore » over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater

Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

NASA Astrophysics Data System (ADS)

Sharma, Gulshan B.; Robertson, Douglas D.

2013-07-01

Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula's material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element's remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than actual

[Paediatric retinal detachment and hereditary vitreoretinal disorders].

PubMed

Meier, P

2013-09-01

The number of retinal detachments in children is very low in comparison to the number in adults. One predisposing factor for development of paediatric retinal detachment is suffering from hereditary vitreoretinal degeneration (e.g., Stickler syndrome, Wagner syndrome, Kniest dysplasia, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, Knobloch syndrome, incontinentia pigmenti, Norrie disease). Hereditary vitreoretinopathies are characterised by an abnormal-appearing vitreous gel with associated retinal changes. In most of these eyes further ocular abnormalities can be diagnosed. A group of hereditary disorders is associated with characteristic systemic abnormalities. Allied conditions should be considered in the clinical diagnosis. Vitreoretinopathies are the most common cause of inherited retinal detachment. In most eyes primary vitrectomy is necessary, and disease-specific surgical treatment is discussed. Georg Thieme Verlag KG Stuttgart · New York.

Unilateral retinitis pigmentosa sine pigmento.

PubMed

Pearlman, J T; Saxton, J; Hoffman, G

1976-05-01

A patient presented with unilateral findings of night blindness shown by impaired rod function and dark adaptation, constricted visual fields with good central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impaired electro-oculogram. There were none of the pigmentary changes usually associated with retinitis pigmentosa. The unaffected right eye was normal in all respects. Therefore the case is most probably one of unilateral retinitis pigmentosa sine pigmento.

ROLE OF TYROSINE-SULFATED PROTEINS IN RETINAL STRUCTURE AND FUNCTION

PubMed Central

Kanan, Y.; Al-Ubaidi, M.R.

2014-01-01

The extracellular matrix (ECM) plays a significant role in cellular and retinal health. The study of retinal tyrosine-sulfated proteins is an important first step toward understanding the role of ECM in retinal health and diseases. These secreted proteins are members of the retinal ECM. Tyrosine sulfation was shown to be necessary for the development of proper retinal structure and function. The importance of tyrosine sulfation is further demonstrated by the evolutionary presence of tyrosylprotein sulfotransferases, enzymes that catalyze proteins’ tyrosine sulfation, and the compensatory abilities of these enzymes. Research has identified four tyrosine-sulfated retinal proteins: fibulin 2, vitronectin, complement factor H (CFH), and opticin. Vitronectin and CFH regulate the activation of the complement system and are involved in the etiology of some cases of age-related macular degeneration. Analysis of the role of tyrosine sulfation in fibulin function showed that sulfation influences the protein's ability to regulate growth and migration. Although opticin was recently shown to exhibit anti-angiogenic properties, it is not yet determined what role sulfation plays in that function. Future studies focusing on identifying all of the tyrosine-sulfated retinal proteins would be instrumental in determining the impact of sulfation on retinal protein function in retinal homeostasis and diseases. PMID:25819460

Correlation of ultra-widefield fundus autofluorescence patterns with the underlying genotype in retinal dystrophies and retinitis pigmentosa.

PubMed

Trichonas, George; Traboulsi, Elias I; Ehlers, Justis P

2017-01-01

Ultra-widefield fundus autofluorescence (UW-FAF) allows the characterization of the peripheral retinal features of vitreoretinal diseases. The purpose of this study was to examine possible genotypic/phenotypic correlations of UW-FAF patterns in patients with a variety of retinal dystrophies and retinitis pigmentosa (RP). An IRB-approved retrospective consecutive case series study was performed of genetically characterized retinal dystrophy or RP patients who underwent UW-FAF imaging. UW-FAF was performed with the Optos 200Tx system. Clinical variables, genotypic analysis, and phenotypic characteristics were reviewed. Seventeen patients were identified who had identified mutations in retinal dystrophy or RP genes and who also had undergone UW-FAF. Three patients had X-linked RP with RPGR mutations. Six patients had autosomal dominant RP (four with RHO mutations and one with a PRPF31 mutation, and one with RDS/PRPH2 mutation). Four patients had autosomal recessive RP (four with USH2A mutations). Three patients had Leber Congenital Amaurosis (LCA) with mutations including CRB1, CEP290, and RPGRIP1. Macular hyperautofluorescence was noted in all patients. A ring of hyperautofluorescence was clear in patients with RHO and USH2A mutations, and patients with USH2A mutations demonstrated a second ring of hyperautofluorescence. In the periphery, patients with RHO or RPGR mutations exhibited hyperautofluorescence with patchy areas of hypoautofluorescence. Patients with USH2A mutations had a distinctive pattern of diffuse and homogeneous peripheral hypoautofluorescence. UW-FAF may provide important information to facilitate diagnosis and further research is needed to better characterize this technology as an imaging biomarker for genotype association in retinal dystrophies and RP.

Human amniotic fluid promotes retinal pigmented epithelial cells' trans-differentiation into rod photoreceptors and retinal ganglion cells.

PubMed

Ghaderi, Shima; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Davari, Maliheh; Jahromi, Fatemeh Sanie; Samie, Shahram; Rezaie-Kanavi, Mozhgan; Pakravesh, Jalil; Deezagi, Abdolkhalegh