Tissue plasminogen activator attenuates outflow facility reduction in mouse model of juvenile open angle glaucoma.
Abstract Tissue plasminogen activator (tPA) has been shown to prevent steroid-induced reduction in aqueous humor outflow facility via an upregulation in matrix metalloproteinase (Mmp) expression. The purpose of this study was to determine whether tPA can rescue outflow facility reduction in the Tg-MYOCY437H mouse model, which replicates human juvenile open angle glaucoma. Outflow facility was measured in Tg-MYOCY437H mice following: periocular steroid exposure and intraocular protein treatment with enzymatically active or enzymatically inactive tPA. Effects of tPA on outflow facility were compared to those of anim...
Source: Experimental Eye Research - July 30, 2020 Category: Opthalmology Authors: Gindina S, Hu Y, Barron AO, Qureshi Z, Danias J Tags: Exp Eye Res Source Type: research

A transcriptomic analysis of diploid and triploid Atlantic salmon lenses with and without cataracts.
, Waagbø R Abstract To avoid negative environmental impacts of escapees and potential inter-breeding with wild populations, the Atlantic salmon farming industry has and continues to extensively test triploid fish that are sterile. However, they often show differences in performance, physiology, behavior and morphology compared to diploid fish, with increased prevalence of vertebral deformities and ocular cataracts as two of the most severe disorders. Here, we investigated the mechanisms behind the higher prevalence of cataracts in triploid salmon, by comparing the transcriptional patterns in lenses of diplo...
Source: Experimental Eye Research - July 28, 2020 Category: Opthalmology Authors: Olsvik PA, Finn RN, Remø SC, Fjelldal PG, Chauvigné F, Glover KA, Hansen T, Waagbø R Tags: Exp Eye Res Source Type: research

Interaction of inflammatorily activated retinal pigment epithelium with retinal microglia and neuronal cells.
In conclusion, inflammatory activated RPE cells have a regulatory effect on the pro-inflammatory activation of microglia, stressing the importance of the interaction between these two retinal cell types. Microglia treated with RPE supernatant reduced viability of a neuronal cell line, indicating a neurotoxic effect. PMID: 32735798 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 28, 2020 Category: Opthalmology Authors: Dietrich L, Lucius R, Roider J, Klettner A Tags: Exp Eye Res Source Type: research

Novel variants in familial exudative vitreoretinopathy patients with KIF11 mutations and the Genotype-Phenotype correlation.
In conclusion: Most (5/9,55.6%) of the causative mutations were frameshift, and nearly half (4/9, 44.4%) of the mutations were de novo. Most (8/9, 88.9%) patients with KIF11 mutations showed typical ocular manifestations of severe FEVR. Majority (6/9, 66.7%) of the probands had a KIF11 mutation and were detected to have microcephaly. Seven of these harbored KIF11 mutations detected to be novel. PMID: 32730767 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 27, 2020 Category: Opthalmology Authors: Chen C, Sun L, Li S, Huang L, Zhang T, Wang Z, Yu B, Luo X, Ding X Tags: Exp Eye Res Source Type: research

Early and late clinical landmarks of corneal dystrophies.
Abstract Corneal dystrophies (CDs) represent a heterogenous group of genetic diseases (Lisch and Weiss, 2019). The International Committee of Classification of Corneal Dystrophies (IC3D) distinguishes between 22 distinct forms of corneal dystrophy (CD) which are predominantly autosomal dominant, although autosomal recessive and X-chromosomal dominant and recessive patterns do exist (Weiss et al, 2018). A detailed corneal examination of as many affected family members as possible can show the phenotypic differences of the various generations. There are few publications which describe the different CDs with regard t...
Source: Experimental Eye Research - July 26, 2020 Category: Opthalmology Authors: Lisch W, Weiss JS Tags: Exp Eye Res Source Type: research

Isoliquiritigenin protects against angiotensin II-induced fibrogenesis by inhibiting NF- κB/PPARγ inflammatory pathway in human Tenon's capsule fibroblasts.
CONCLUSION: ISL could alleviate ANG II-induced fibrogenesis by inhibiting the NF-κB/PPARγ inflammatory pathway. In addition, ISL may be a potential agent for the treatment of conjunctival fibrosis. Most importantly, the NF-κB/PPARγ signaling pathway could be an effective therapeutic target for the prevention and treatment of conjunctival fibrosis after glaucoma surgery. PMID: 32726604 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 26, 2020 Category: Opthalmology Authors: Ye H, Xi Y, Chen X, Shen L, Le R Tags: Exp Eye Res Source Type: research

Animal models of high-risk corneal transplantation: A comprehensive review.
Abstract Over the past century, corneal transplantation has become the most commonly performed allogeneic solid tissue transplantation. Although more than 80% of the corneal transplantations have favorable outcomes, immune-mediated rejection continues to be the major cause of failure in well over 50% of graft recipients that have inflamed and vascularized host beds. Over the past two decades, the progress in our understanding of the immunological pathways that mediate graft rejection has aided in the development of novel therapeutic strategies. In order to successfully test the efficacy of these interventions, it ...
Source: Experimental Eye Research - July 25, 2020 Category: Opthalmology Authors: Singh RB, Marmalidou A, Amouzegar A, Chen Y, Dana R Tags: Exp Eye Res Source Type: research

PEDF deficiency increases the susceptibility of rd10 mice to retinal degeneration.
Abstract The SERPINF1 gene encodes pigment epithelium-derived factor (PEDF), a member of the serpin superfamily with neurotrophic and antiangiogenic properties in the retina. We hypothesized that absence of PEDF would lead to increased stress-associated retinal degeneration in Serpinf1 null mice. Accordingly, using a Serpinf1 null mouse model, we investigated the impact of PEDF absence on retinal morphology, and susceptibility to induced and inherited retinal degeneration. We studied the pattern of Serpinf1 expression in the mouse retina layers. PEDF protein was detected by western blotting. Transmission electron ...
Source: Experimental Eye Research - July 25, 2020 Category: Opthalmology Authors: Dixit S, Polato F, Samardzija M, Abu-Asab M, Grimm C, Crawford SE, Becerra SP Tags: Exp Eye Res Source Type: research

Hyaluronic acid coating of gold nanoparticles for intraocular drug delivery: Evaluation of the surface properties and effect on their distribution.
In this study, the combination of gold and HA enhanced the stability of the whole carrier and promoted their distribution across ocular tissues and barriers to reach the retina. Moreover, analysis in vitro, ex vivo, and in ovo revealed the protective and antiangiogenic effect of GNPs as inhibitors of AGEs-mediated- retinal pigment epithelial cell death and neovascularization. We demonstrated that conjugation with HA enhances GNP stability and distribution due to a specific CD44 receptor interaction. The capacity of HA-GNPs to distribute through the vitreous humour and their avidity for the deeper retinal layers ex vivo, su...
Source: Experimental Eye Research - July 25, 2020 Category: Opthalmology Authors: Apaolaza PS, Busch M, Asin-Prieto E, Peynshaert K, Rathod R, Remaut K, Dünker N, Göpferich A Tags: Exp Eye Res Source Type: research

Identification of the aberrantly methylated differentially expressed genes in proliferative diabetic retinopathy.
In conclusion, the present study identified an association among DNA methylation and gene expression in PDR using bioinformatics analysis, and identified the hub genes which might be potential methylation-based diagnosis and treatment targets for PDR in the near future. PMID: 32721427 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 25, 2020 Category: Opthalmology Authors: Miao A, Lu J, Wang Y, Mao S, Cui Y, Pan J, Li L, Luo Y Tags: Exp Eye Res Source Type: research

A signal for defocus for emmetropization arising from longitudinal chromatic aberration in chick.
Abstract Chicks respond to two signals from longitudinal chromatic aberration (LCA): a wavelength defocus signal and a chromatic signal. Wavelength defocus predicts reduced axial eye growth in monochromatic short-wavelength light, compared to monochromatic long-wavelength light. Wavelength defocus may also influence growth in broadband light. In contrast, a chromatic signal predicts increased growth when short-wavelength contrast > long-wavelength contrast, but only when light is broadband. We aimed to investigate the influence of blue light, temporal frequency and contrast on these signals under broa...
Source: Experimental Eye Research - July 24, 2020 Category: Opthalmology Authors: Rucker FJ, Eskew RT, Taylor C Tags: Exp Eye Res Source Type: research

Retinal changes in mice spontaneously developing diabetes by Th17-cell deviation.
In this study, Ins2Akita IFN-γ-deficient (Akita-GKO) mice were established by crossbreeding Akita mice with GKO mice, and Th17-mediated immune responses on DR were investigated. Blood glucose levels (BGL) of Akita mice and Akita-GKO mice were significantly higher than those of age-matched wild type (WT) or GKO mice, and there was no significant difference in BGL between Akita and Akita-GKO mice. Relative mRNA expression of ROR-γt that is a transcriptional factor of Th17 cells but not GATA-3 that is for Th2 cells was significantly upregulated only in Akita-GKO mice compared with WT mice, and the proportions of...
Source: Experimental Eye Research - July 24, 2020 Category: Opthalmology Authors: Taguchi M, Someya H, Inada M, Nishio Y, Takayama K, Harimoto K, Karasawa Y, Ito M, Takeuchi M Tags: Exp Eye Res Source Type: research

Quantitative analysis of astrocyte and axonal density relationships: Glia to neuron ratio in the optic nerve laminar regions.
This study demonstrates that the distribution of astrocytes correlates closely with the density of axonal processes, in accordance with the functional requirement of different regions of the ganglion cell axon. There was a consistency of glia-neuron ratios in the majority of laminar compartments, except for the human and rat prelaminar regions, which demonstrated lower ratios of astrocyte to axonal processes. The distribution of astrocytes may reflect a functional susceptibility to development of disease in the prelaminar region of the optic nerve. Interspecies comparison at the lamina cribrosa showed strikingly consistent...
Source: Experimental Eye Research - July 23, 2020 Category: Opthalmology Authors: Chan G, Morgan WH, Yu DY, Balaratnasingam C Tags: Exp Eye Res Source Type: research

Transport and fate of aflibercept in VEGF-A165-challenged retinal endothelial cells.
Abstract Retinal vessels are at least in part involved in clearing of Fc terminus-containing proteins from the vitreous. In vitro, the Fc fusion protein aflibercept is transported through a monolayer of unchallenged immortalized bovine retinal endothelial cells (iBREC), mediated by the neonatal Fc receptor (FcRn), but part of the Fc fusion protein is also degraded. Aflibercept's target VEGF-A not only enhances the permeability of REC by destabilization of tight junctions (TJs) thereby allowing for paracellular flow, it may also lower the intracellular stability of the Fc fusion protein by changing its binding prop...
Source: Experimental Eye Research - July 23, 2020 Category: Opthalmology Authors: Deissler HL, Sommer K, Lang GK, Lang GE Tags: Exp Eye Res Source Type: research

Claudins regulate gene and protein expression of the retinal pigment epithelium independent of their association with tight junctions.
In conclusion, claudins can increase the barrier function of a pre-existing apical junctional complex, but on its own it cannot recruit tight junction proteins to form a complex de novo. Many effects of claudin on gene expression did not require an association with the apical junctional complex. Although claudin-19 shared many effects with claudin-3, claudin-19 exerted unique effects on the maturation of RPE. PMID: 32712183 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 23, 2020 Category: Opthalmology Authors: Liu F, Xu T, Peng S, Adelman RA, Rizzolo LJ Tags: Exp Eye Res Source Type: research

Integrin: Basement membrane adhesion by corneal epithelial and endothelial cells.
MA Abstract Integrins mediate adhesion of cells to substrates and maintain tissue integrity by facilitating mechanotransduction between cells, the extracellular matrix, and gene expression in the nucleus. Changes in integrin expression in corneal epithelial cells and corneal endothelial cells impacts their adhesion to the epithelial basement membrane (EpBM) and Descemet's membrane, respectively. Integrins also play roles in assembly of basement membranes by both activating TGFβ1 and other growth factors. Over the past two decades, this knowledge has been translated into methods to grow corneal epithelial and...
Source: Experimental Eye Research - July 23, 2020 Category: Opthalmology Authors: McKay TB, Schlötzer-Schrehardt U, Pal-Ghosh S, Stepp MA Tags: Exp Eye Res Source Type: research

Microtubule alterations may destabilize photoreceptor integrity age-related microtubule changes and pattern of expression of MAP-2, Tau and hyperphosphorylated Tau in aging human photoreceptor cells.
This study examined photoreceptor cell ultrastructure from 18 human donor retinas (32 eyes; age: 45-94 years) and quantified the photoreceptors with altered microtubules over six to ninth decades in four defined retinal regions. In addition, immunoreactivity (IR) to microtubule-associated protein-2 (MAP-2), tau and hyperphophorylated tau was performed in retinal sections from companion eyes. In young donor retinas below 75 years of age, microtubules appeared straight in photoreceptor inner segments and axons. With age, they appeared bent or misaligned in macular and mid-peripheral photoreceptors. In addition, dense granula...
Source: Experimental Eye Research - July 22, 2020 Category: Opthalmology Authors: Nag TC, Kathpalia P, Wadhwa S Tags: Exp Eye Res Source Type: research

Detailed comparison of phenotype between male patients carrying variants in exons 1-14 and ORF15 of RPGR.
Abstract PURPOSE: To compare disease severity in detail between patients carrying variants in exons 1-14 and ORF15 of retinitis pigmentosa GTPase regulator (RPGR). METHODS: Systematic next-generation sequencing data analysis, Sanger sequencing validation and segregation analysis were utilised to identify the pathogenic variants. Detailed ophthalmic examinations, including electroretinograms, fundus photography, fundus autofluorescence and optical coherence tomography were performed. Statistical analysis, including age adjustment and comparison, were performed based on cross-sectional level to compare disease ...
Source: Experimental Eye Research - July 20, 2020 Category: Opthalmology Authors: Zou X, Fang S, Wu SJ, Li H, Sun ZX, Zhu T, Wei X, Sui RF Tags: Exp Eye Res Source Type: research

Ocular pathology in NeuroAIDS - An autopsy study.
Abstract The central nervous system (CNS) and the eye are involved in Human immunodeficiency virus related disease. Although, optic nerve is considered an extension of the CNS, it has not been systematically evaluated to determine if infections of brain can extend into the eye or vice versa. The brain and posterior compartment of eyeball retrieved at autopsy of patients succumbing to NeuroAIDS, were evaluated with Hematoxylin & Eosin, special stains and immunohistochemistry for infective pathogens. Multiplex PCR was performed in vitreous, CSF and serum for simultaneous detection of bacterial, viral, and protoz...
Source: Experimental Eye Research - July 20, 2020 Category: Opthalmology Authors: Mhatre R, Govekar S, Nandeesh BN, Lakshman LP, Banda R, P S, Sk S, Anita M Tags: Exp Eye Res Source Type: research

Corneal epithelial biology: Lessons stemming from old to new.
Abstract The anterior surface of the eye functions as a barrier to the external environment and protects the delicate underlying tissues from injury. Central to this protection are the corneal, limbal and conjunctival epithelia. The corneal epithelium is a self-renewing stratified squamous epithelium that protects the underlying delicate structures of the eye, supports a tear film and maintains transparency so that light can be transmitted to the interior of the eye (Basu et al., 2014; Cotsarelis et al., 1989; Funderburgh et al., 2016; Lehrer et al., 1998; Pajoohesh-Ganji and Stepp, 2005; Parfitt et al., 2015; Pen...
Source: Experimental Eye Research - July 19, 2020 Category: Opthalmology Authors: Lavker RM, Kaplan N, Wang J, Peng H Tags: Exp Eye Res Source Type: research

Asymmetrical influence of a standard light/dark cycle and constant light conditions on the alanyl-aminopeptidase activity of the left and right retinas in adult male rats.
M, Ramírez-Sánchez M Abstract The retina acts as an independent clock informing the central pacemaker, the suprachiasmatic nucleus, under environmental light conditions, with consequences of such inputs for the central and peripheral nervous system. Differences in the behavior of the left and right retinas depending on environmental light conditions may influence the information projected to the brain hemispheres. The retina possesses neuropeptides that act as neurotransmitters or neuromodulators. Alanyl-aminopeptidase (AlaAP, EC 3.4.11.2) activity regulates some of these neuropeptides and therefore...
Source: Experimental Eye Research - July 18, 2020 Category: Opthalmology Authors: Domínguez-Vías G, Aretxaga G, Prieto I, Segarra AB, Luna JD, Martínez-Cañamero M, Ramírez-Sánchez M Tags: Exp Eye Res Source Type: research

Localization of the lens intermediate filament switch by imaging mass spectrometry.
In this study, a method was developed for imaging low solubility cytoskeletal proteins in the lens; a tissue that is filled with high concentrations of soluble crystallins. Optimized tissue washes combined with on-tissue enzymatic digestion allowed successful imaging of peptides corresponding to known lens cytoskeletal proteins. The resulting peptide signals facilitated segmentation of the bovine lens into molecularly distinct regions. A sharp intermediate filament transition from vimentin to lens-specific beaded filament proteins was detected in the lens cortex. MALDI IMS also revealed the region where posttranslational m...
Source: Experimental Eye Research - July 16, 2020 Category: Opthalmology Authors: Wang Z, Ryan DJ, Schey KL Tags: Exp Eye Res Source Type: research

Circular RNA HIPK3 regulates human lens epithelial cell dysfunction by targeting the miR-221-3p/PI3K/AKT pathway in age-related cataract.
Abstract Circular RNA Homeodomain Interacting Protein Kinase 3 (circHIPK3) was found to involve in the pathogenesis of age-related cataract (ARC). Here, we further disclosed the related target genes and molecular mechanism of circHIPK3 in the ARC progression. The expression of circHIPK3, microRNA (miR)-221-3p was detected using the quantitative real-time polymerase chain reaction. Human lens epithelial cell (HLEC) proliferation and apoptosis were measured by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay and flow cytometry, respectively. Western blot was used to detect the levels of ...
Source: Experimental Eye Research - July 15, 2020 Category: Opthalmology Authors: Cui G, Wang L, Huang W Tags: Exp Eye Res Source Type: research

In Memoriam, James D. Zieske, Ph.D. (1954-2020).
PMID: 32668283 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 12, 2020 Category: Opthalmology Authors: Wilson SE Tags: Exp Eye Res Source Type: research

In Memoriam James L. Funderburgh, PhD (1935 to 2019).
PMID: 32668284 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 12, 2020 Category: Opthalmology Authors: Conrad GW, Brychta LJ, Wilson SE Tags: Exp Eye Res Source Type: research

12. Endothelial pump and barrier function.
Abstract The mammalian cornea maintains its thickness and transparency primarily by the activity of a fluid pump located in the endothelial cell layer. The accepted concept, the "pump-leak" theory, holds that the active transport of solute from the stroma to the aqueous humor leads to a steady state osmotic pressure gradient across the endothelium that balances the imbibition pressure created by the hydrophilic proteoglycans in the stromal ground substance. The details of this process are controversial and some of the classical in vitro studies aimed to explore the fluid pump using low temperature to cha...
Source: Experimental Eye Research - July 11, 2020 Category: Opthalmology Authors: Klyce SD Tags: Exp Eye Res Source Type: research

Composition, structure and function of the corneal stroma.
Abstract No other tissue in the body depends more on the composition and organization of the extracellular matrix (ECM) for normal structure and function than the corneal stroma. The precise arrangement and orientation of collagen fibrils, lamellae and keratocytes that occurs during development and is needed in adults to maintain stromal function is dependent on the regulated interaction of multiple ECM components that contribute to attain the unique properties of the cornea: transparency, shape, mechanical strength, and avascularity. This review summarizes the contribution of different ECM components, their struc...
Source: Experimental Eye Research - July 11, 2020 Category: Opthalmology Authors: Espana EM, Birk DE Tags: Exp Eye Res Source Type: research

Biology of keratorefractive surgery- PRK, PTK, LASIK, SMILE, inlays and other refractive procedures.
This article details what is known about these specific wound healing responses that include apoptosis of keratocytes and myofibroblasts, mitosis of corneal fibroblasts and myofibroblast precursors, the development of myofibroblasts from keratocyte-derived corneal fibroblasts and bone marrow-derived fibrocytes, deposition of disordered extracellular matrix by myofibroblasts, healing of the epithelial injury, and regeneration of the epithelial basement membrane. Problems with epithelial and stromal cellular viability and function that are altered by corneal inlays are also discussed. A better understanding of the wound heal...
Source: Experimental Eye Research - July 9, 2020 Category: Opthalmology Authors: Wilson SE Tags: Exp Eye Res Source Type: research

Welcome to the first Corneal Special Issue.
PMID: 32649950 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 7, 2020 Category: Opthalmology Authors: Wilson SE Tags: Exp Eye Res Source Type: research

Metabolic signature of eyelid basal cell carcinoma.
In conclusion, eyelid BCC has a signature change of cell metabolome. Metabolites in NAD metabolic pathways could potentially be biomarkers or therapeutic targets for eyelid BCC. PMID: 32649951 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 7, 2020 Category: Opthalmology Authors: Huang J, Schaefer J, Wang Y, Gioia L, Pei Y, Shi X, Waris S, Zhao C, Nguyen J, Du J Tags: Exp Eye Res Source Type: research

Retinal ischemia triggers early microglia activation in the optic nerve followed by neurofilament degeneration.
In this study, retinal ischemia was induced in one eye of Brown-Norway rats by raising the intraocular pressure 60 min to 140 mmHg followed by natural reperfusion. Optic nerves were analyzed at six different points in time: 2, 6, 12, and 24 h as well as 3 and 7 days after ischemic injury. Cell infiltration and moreover signs of tissue demyelination and dissolution were noticed in optic nerves 7 days after ischemia (hematoxylin & eosin: p 
Source: Experimental Eye Research - July 6, 2020 Category: Opthalmology Authors: Palmhof M, Wagner N, Nagel C, Biert N, Stute G, Dick HB, Joachim SC Tags: Exp Eye Res Source Type: research

Intravitreal enzyme replacement inhibits progression of retinal degeneration in canine CLN2 neuronal ceroid lipofuscinosis.
Abstract CLN2 neuronal ceroid lipofuscinosis is a rare recessive hereditary retinal and neurodegenerative disease resulting from deleterious sequence variants in TPP1 that encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Children with this disorder develop normally, but starting at 2-4 years of age begin to exhibit neurological signs and visual deficits. Vision loss that progresses to blindness is associated with progressive retinal degeneration and impairment of retinal function. Similar progressive loss of retinal function and retinal degeneration occur in a dog CLN2 disease model with a TPP1...
Source: Experimental Eye Research - July 4, 2020 Category: Opthalmology Authors: Whiting REH, Robinson GO, Ota-Kuroki J, Lim S, Castaner LJ, Jensen CA, Kowal J, Nguyen A, Corado C, O'Neill CA, Katz ML Tags: Exp Eye Res Source Type: research

Hypoxia regulates the degradation of non-nuclear organelles during lens differentiation through activation of HIF1a.
Abstract Formation of the eye lens depends on the continuous differentiation of lens epithelial cells into lens fiber cells. To attain their mature structure and transparent function, nascent lens fiber cells must complete a precise cellular remodeling program hallmarked by the complete elimination of organelles to form the core lens organelle-free zone (OFZ). Lacking a blood supply, the lens resides in a hypoxic environment that results in a decreasing oxygen concentration from the lens surface to the lens core. This oxygen gradient results in a hypoxic microenvironment in the region of the lens where immature le...
Source: Experimental Eye Research - July 3, 2020 Category: Opthalmology Authors: Brennan L, Disatham J, Kantorow M Tags: Exp Eye Res Source Type: research

mTORC1 and mTORC2 expression in inner retinal neurons and glial cells.
This study was undertaken to: 1) quantify expression of mTOR complex 1 (mTORC1)- and mTORC2-specific partner proteins in normal adult rat retina, brain and liver; and 2) to localize these components in normal human, rat, and mouse retinas. Immunoblotting and immunoprecipitation studies revealed greater expression of raptor (exclusive to mTORC1) and rictor (exclusive for mTORC2) in normal rat retina relative to liver or brain, as well as the activating mTORC components, pSIN1 and pPRAS40. By contrast, liver exhibits greater amounts of the mTORC inhibitor, DEPTOR. Immunolocalization studies for all three species showed that ...
Source: Experimental Eye Research - July 2, 2020 Category: Opthalmology Authors: Losiewicz MK, Elghazi L, Fingar DC, Rajala RVS, Lentz SI, Fort PE, Abcouwer SF, Gardner TW Tags: Exp Eye Res Source Type: research

Intravitreal enzyme replacement preserves retinal structure and function in canine CLN2 neuronal ceroid lipofuscinosis.
Abstract CLN2 neuronal ceroid lipofuscinosis is a hereditary neurodegenerative disorder characterized by progressive vision loss, neurological decline, and seizures. CLN2 disease results from mutations in TPP1 that encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Children with CLN2 neuronal ceroid lipofuscinosis experience ocular disease, characterized by progressive retinal degeneration associated with impaired retinal function and gradual vision loss culminating in total blindness. A similar progressive loss of retinal function is also observed in a dog CLN2 model with a TPP1 null mutation. A study w...
Source: Experimental Eye Research - July 1, 2020 Category: Opthalmology Authors: Whiting REH, Pearce JW, Vansteenkiste DP, Bibi K, Lim S, Robinson GO, Castaner LJ, Sinclair J, Chandra S, Nguyen A, O'Neill CA, Katz ML Tags: Exp Eye Res Source Type: research

Evaluation of reconstructed human corneal endothelium sheets made with porcine Descemet's membrane in vitro and in vivo.
CONCLUSIONS: Seeding non-infected monoclonal HCECs on porcine DM could reconstruct functional corneal endothelial sheets. These results may help uncover new applications for tissue-engineered endothelium in endothelial keratoplasty. PMID: 32622067 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 1, 2020 Category: Opthalmology Authors: Lu Q, Peng RM, Feng N, Wen MD, He LH, Hong J Tags: Exp Eye Res Source Type: research

Modeling the cornea in 3-dimensions: Current and future perspectives.
We describe current methods to model the human cornea with focus on organotypic approaches, compressed collagen, bioprinting, and self-assembled stromal models. We also expand on co-culture applications with the inclusion of relevant corneal cell types, such as epithelial, stromal keratocyte or fibroblast, endothelial, and neuronal cells. Further advancements in corneal tissue model development will markedly improve our current understanding of corneal wound healing and regeneration. PMID: 32619578 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - June 30, 2020 Category: Opthalmology Authors: McKay TB, Hutcheon AEK, Guo X, Zieske JD, Karamichos D Tags: Exp Eye Res Source Type: research

Determination of peripapillary vessel density in optic disc drusen using EDI-OCT and OCT angiography.
This study proposes a method to determine the vessel density in OCTA scans in general and especially the local peripapillary vessel density. The method produces vessel density heatmaps that contain information about the local vessel density. We apply the method in a small study to demonstrate its applicability and its potential to investigate the influence of local conditions on the vessel density. In the study, we combine information from enhanced depth imaging optical coherence tomography (EDI-OCT) about the location of optic disc drusen (ODD) with information from OCTA about the vessel density. We see a reduction in loc...
Source: Experimental Eye Research - June 30, 2020 Category: Opthalmology Authors: Lindberg AW, Dahl VA, Karlesand I, Rueløkke LL, Malmqvist L, Hamann S Tags: Exp Eye Res Source Type: research

Comment on 'A method to quantify regional axonal transport blockade at the optic nerve head after short term intraocular pressure elevation in mice by A. Korneva et al. '(Exp. Eye Res. doi: https://doi.org/10.1016/j.exer.2020.108035).
PMID: 32619580 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - June 30, 2020 Category: Opthalmology Authors: Casson RJ, Chidlow G, Wood J Tags: Exp Eye Res Source Type: research

Reorganization of the perifoveal microvasculature after macular hole closure assessed via optical coherence tomography angiography.
CONCLUSIONS: IMH closure after PPV and ILM peeling caused a significantly improved microvasculature in the deep capillary plexus, which may represent reorganized perifoveal microvasculature due to the regression of cystoid spaces. PMID: 32615122 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - June 29, 2020 Category: Opthalmology Authors: Lauermann P, Dülk J, van Oterendorp C, Hoerauf H, Feltgen N, Bemme S Tags: Exp Eye Res Source Type: research

Epigallocatechin-3-gallate (EGCG) inhibits myofibroblast transformation of human Tenon's fibroblasts.
This study was conducted to investigate the effect of EGCG on TGF-β1-induced myofibroblast transformation of human Tenon's fibroblasts. The human Tenon's fibroblasts were incubated in the medium containing 10 ng/mL TGF-β1, and subsequently treated with EGCG or mitomycin C (MMC). The cell proliferation and migration were analyzed. The expression of alpha-smooth muscle actin (α-SMA), type I collagen (Col-I), and p-Smad2/3 were also evaluated. It showed that EGCG and MMC strongly inhibited the elevation in cell number in tissue explants compared to the tissues treated with TGF-β1 alone. Scratch-Wound as...
Source: Experimental Eye Research - June 27, 2020 Category: Opthalmology Authors: Lin HL, Qin YJ, Zhang YL, Zhang YQ, Chen YL, Niu YY, Pang CP, Chu WK, Zhang HY Tags: Exp Eye Res Source Type: research

Targeted delivery of mitomycin C-loaded and LDL-conjugated mesoporous silica nanoparticles for inhibiting the proliferation of pterygium subconjunctival fibroblasts.
In this study, we designed and synthesized MMC-loaded mesoporous silica nanoparticles conjugated with LDL (MMC@MSNs-LDL) to deliver MMC into activated pterygium fibroblasts in a targeted manner. The MMC loading efficiency was approximately 6%. The cell viability test (CCK-8 assay) revealed no cytotoxicity for the empty carrier MSNs at a concentration of ≤1 mg/ml after administration for 48 h in subconjunctival fibroblasts. Primary pterygium and normal human subconjunctival fibroblasts with or without stimulation by vascular endothelial growth factor (VEGF) were treated as follows: 1) 10 μg/ml MMC@MSNs-LDL for 2...
Source: Experimental Eye Research - June 26, 2020 Category: Opthalmology Authors: Wu M, Wang S, Wang Y, Zhang F, Shao T Tags: Exp Eye Res Source Type: research

In vivo evaluation of retinal ganglion cells and optic nerve's integrity in large animals by multi-modality analysis.
Abstract Large animal models of optic nerve injury are essential for translating novel findings into effective therapies due to their similarity to humans in many respects. However, most current tests evaluating the integrity of retinal ganglion cells (RGCs) and optic nerve (ON) are based on rodent animal models. We aimed to evaluate and optimize the in vivo methods to assess RGCs and ON's function and structure in large animals in terms of reproducibility, simplicity and sensitivity. Bothe goats and rhesus macaques were employed in this study. By using goats, we found anesthesia with isoflurane or xylazine result...
Source: Experimental Eye Research - June 26, 2020 Category: Opthalmology Authors: Zhang Y, Zhang S, Xia Y, Ji Y, Jiang W, Li M, Huang H, Xu M, Sun J, Ye Q, Hu Y, Wu W Tags: Exp Eye Res Source Type: research

Deconstructing aqueous humor outflow - The last 50 years.
Abstract Herein partially summarizes one scientist-clinician's wanderings through the jungles of primate aqueous humor outflow over the past ∼45 years. Totally removing the iris has no effect on outflow facility or its response to pilocarpine, whereas disinserting the ciliary muscle (CM) from the scleral spur/trabecular meshwork (TM) completely abolishes pilocarpine's effect. Epinephrine increases facility in CM disinserted eyes. Cytochalasins and latrunculins increase outflow facility, subthreshold doses of cytochalasins and epinephrine given together increase facility, and phalloidin, which has no effect on ...
Source: Experimental Eye Research - June 23, 2020 Category: Opthalmology Authors: Kaufman PL Tags: Exp Eye Res Source Type: research

The retinal tyrosine kinome of diabetic Akimba mice highlights potential for specific SRC family kinase inhibition in retinal vascular disease.
Abstract Although anti-VEGF therapies have radically changed clinical practice, there is still an urgent demand for novel, integrative approaches for sight-threatening retinal vascular diseases. As we hypothesize that protein tyrosine kinases are key signaling mediators in retinal vascular disease, we performed a comprehensive activity-based tyrosine kinome profiling on retinal tissue of 12-week old Akimba mice, a translational model displaying hallmarks of early and advanced diabetic retinopathy. Western blotting was used to confirm retinal tyrosine kinase activity in Akimba mice. HUVEC tube formation and murine ...
Source: Experimental Eye Research - June 23, 2020 Category: Opthalmology Authors: Sergeys J, Van Hove I, Hu TT, Temps C, Carragher NO, Unciti-Broceta A, Feyen JHM, Moons L, Porcu M Tags: Exp Eye Res Source Type: research

Gene expression profiling of tumor stroma interactions in retinoblastoma.
Abstract We aimed to identify the critical molecular pathways altered upon tumor stroma interactions in retinoblastoma (RB). In vitro 2 D cocultures of RB tumor cells (Weri-Rb-1 and NCC-RbC-51) with primary bone marrow stromal cells (BMSC) was established. Global gene expression patterns in coculture samples were assessed using Affymetrix Prime view human gene chip microarray and followed with bioinformatics analyses. Key upregulated genes from Weri-Rb-1 + BMSC and NCC-RbC-51 + BMSC coculture were validated using qRT-PCR to ascertain their role in RB progression. Whole genome microarray experim...
Source: Experimental Eye Research - June 22, 2020 Category: Opthalmology Authors: Raguraman R, Parameswaran S, Kanwar JR, Vasudevan M, Chitipothu S, Kanwar RK, Krishnakumar S Tags: Exp Eye Res Source Type: research

Viral delivery of multiple miRNA promotes retinal ganglion cell survival and functional preservation after optic nerve crush injury.
Abstract Bone marrow mesenchymal stem cell (BMSC)-derived small extracellular vesicles (sEV) but not fibroblast sEV provide retinal ganglion cell (RGC) neuroprotection both in vitro and in vivo, with miRNAs playing an essential role. More than 40 miRNAs were more abundant in BMSC-sEV than in fibroblast-sEV. The purpose of this study was to test the in vitro and in vivo neuroprotective and axogenic properties of six candidate miRNAs (miR-26a, miR-17, miR-30c-2, miR-92a, miR-292, and miR-182) that were more abundant in BMSC-sEV than in fibroblast-sEV. Adeno-associated virus (AAV)-2 expressing a combination of three ...
Source: Experimental Eye Research - June 20, 2020 Category: Opthalmology Authors: Mead B, Cullather E, Nakaya N, Niu Y, Kole C, Ahmed Z, Tomarev S Tags: Exp Eye Res Source Type: research

Biomechanical effect of ultraviolet-A-riboflavin cross-linking on simulated human corneal stroma model and its correlation with changes in corneal stromal microstructure.
In this study, we established an experimental human corneal stroma model of simulated cornea tissue composed of thin anterior cornea strips layers obtained from small incision lenticular extraction (SMILE) surgery. We investigated the biomechanical effect of ultraviolet-A- riboflavin cross-linking at different depths of corneal stroma model and correlated it with stromal microstructural changes examined by transmission electron microscopy (TEM). Corneal strips were harvested from fresh human corneal lenticules obtained after SMILE surgery. Experimental models (n = 31) were established by superimposing the corneal lenti...
Source: Experimental Eye Research - June 18, 2020 Category: Opthalmology Authors: Li H, Liu T, Mu B, Zhao X, Xue C, Shen M, Jhanji V, Wang Y Tags: Exp Eye Res Source Type: research

Galectins and their involvement in ocular disease and development.
Abstract Galectins are carbohydrate binding proteins with high affinity to ß-galactoside containing glycoconjugates. Understanding of the functions of galectins has grown steadily over the past decade, as a result of substantial advancements in the field of glycobiology. Galectins have been shown to be versatile molecules that participate in a range of important biological systems, including inflammation, neovascularisation and fibrosis. These processes are of particular importance in ocular tissues, where a major theme of recent research has been to divert diseases away from pathways which result in loss of...
Source: Experimental Eye Research - June 18, 2020 Category: Opthalmology Authors: Luis J, Eastlake K, Khaw PT, Limb GA Tags: Exp Eye Res Source Type: research

Evaluation of the genetic association between early-onset primary angle-closure glaucoma and retinitis pigmentosa.
Abstract Primary angle-closure glaucoma (PACG) and retinitis pigmentosa (RP) can co-occur, but the mechanism of their association is not yet established. The purpose of this study was to investigate the differences in ocular biometry parameters and molecular genetics in patients with PACG with or without RP, and to determine the association between PACG and RP. Patients with early-onset PACG (age of onset
Source: Experimental Eye Research - June 17, 2020 Category: Opthalmology Authors: Liu X, Li J, Lin S, Xiao X, Luo J, Wei W, Ling Y, Fang L, Xiao H, Chen L, Huang J, Zhong Y, Zhang Q Tags: Exp Eye Res Source Type: research