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RNA therapeutics in ophthalmology - translation to clinical trials.
Abstract The use of RNA interference technology has proven to inhibit the expression of many target genes involved in the underlying pathogenesis of several diseases affecting various systems. First established in in vitro and later in animal studies, small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapeutics are now entering clinical trials with the potential of clinical translation to patients. Gene-silencing therapies have demonstrated promising responses in ocular disorders, predominantly due to the structure of the eye being a closed and compartmentalised organ. However, although the effic...
Source: Experimental Eye Research - February 3, 2021 Category: Opthalmology Authors: Gupta A, Kafetzis KN, Tagalakis AD, Yu-Wai-Man C Tags: Exp Eye Res Source Type: research

Receptor potential channels TRPC1/TRPC6 regulate lamina cribrosa cell extracellular matrix gene transcription and proliferation.
In conclusion, TRPC1/C6 expression is enhanced in glaucoma LC cells. These channels may contribute to oxidative stress-induced ECM gene transcription and cell proliferation in normal and glaucoma LC cells through Ca2+-NFATc3 signaling pathway mechanism. TRPC1 and TRPC6 channels could be important therapeutic targets to prevent ECM remodeling and fibrosis development in glaucoma optic neuropathy. PMID: 32088241 [PubMed - as supplied by publisher]
Source: Experimental Eye Research - February 19, 2020 Category: Opthalmology Authors: Irnaten M, O'Malley G, Clark AF, O'Brien CJ Tags: Exp Eye Res Source Type: research

Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review.
Authors: Lanza M, Benincasa G, Costa D, Napoli C Abstract Network medicine is a molecular-bioinformatic approach analyzing gene-gene interactions that can perturb the human interactome. This review focuses on epigenetic changes involved in several ocular diseases, such as DNA methylation, histone and nonhistone post-translational modifications, and noncoding RNA regulators. Although changes in aberrant DNA methylation play a major role in the pathogenesis of most ocular diseases, histone modifications are seldom investigated. Hypermethylation in TGM-2 and hypomethylation in MMP-2/CD24 promoter genes may play a cruc...
Source: Journal of Ophthalmology - January 25, 2020 Category: Opthalmology Tags: J Ophthalmol Source Type: research

Expression of retinoic acid signaling components ADH7 and ALDH1A1 is reduced in aniridia limbal epithelial cells and a siRNA primary cell based aniridia model.
Abstract PAX6-related Aniridia is a sight-threatening disease involving progression of secondary glaucoma and aniridia related keratopathy (ARK). Change or loss of limbal epithelial progenitors causes epithelial surface defects. We analyzed the effect of PAX6 on mRNA expression changes with a two-step approach, as follows. First, we sequenced mRNA from limbal epithelial cells isolated from controls and aniridia patients. Second, we confirmed the bioinformatics and literature-based result list for a small interfering RNA (siRNA)-based primary aniridia cell model (PAX6 knockdown). With this approach, we expected tha...
Source: Experimental Eye Research - October 4, 2018 Category: Opthalmology Authors: Latta L, Nordström K, Stachon T, Langenbucher A, Fries FN, Szentmáry N, Seitz B, Käsmann-Kellner B Tags: Exp Eye Res Source Type: research

Contribution of the clock gene DEC2 to VEGF mRNA upregulation by modulation of HIF1 α protein levels in hypoxic MIO-M1 cells, a human cell line of retinal glial (Müller) cells
ConclusionDEC2 could upregulate retinalVEGF gene expression through modulation of HIF1 α levels under hypoxic conditions.
Source: Japanese Journal of Ophthalmology - September 24, 2018 Category: Opthalmology Source Type: research

Targeted therapy for the post-operative conjunctiva: SPARC silencing reduces collagen deposition.
CONCLUSIONS: SPARC targeted therapy effectively reduced both SPARC and collagen production in the operated mouse conjunctiva. This proof-of-concept study suggests that targeted treatment of fibrosis in glaucoma surgery is safe and feasible, with the potential to extend to a range of potential genes associated with fibrosis. PMID: 30021812 [PubMed - as supplied by publisher]
Source: The British Journal of Ophthalmology - July 18, 2018 Category: Opthalmology Authors: Seet LF, Tan YF, Toh LZ, Chu SW, Lee YS, Venkatraman SS, Wong TT Tags: Br J Ophthalmol Source Type: research

Beta2 adrenergic receptor silencing change intraocular pressure in New Zealand rabbits
ConclusionThe use of siRNA against the beta2 adrenergic receptors could provide an interesting therapeutic strategy for glaucoma treatment.ResumenObjetivoEl glaucoma consiste en un grupo de neuropatías ópticas progresivas caracterizadas por degeneración del nervio óptico y pérdida irreversible del campo visual. La elevación de la presión intraocular es el único factor de riesgo tratable probado, centrándose los productos comerciales para el tratamiento del glaucoma en la reducción de la presión intraocular. Estos fármacos pueden tener diversos efectos secundarios indeseados, lo cual invita a buscar nuevas estra...
Source: Journal of Optometry - July 10, 2018 Category: Opthalmology Source Type: research

Gene transfer to the outflow tract.
Abstract Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm's canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15-20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affec...
Source: Experimental Eye Research - April 26, 2016 Category: Opthalmology Authors: Dang Y, Loewen R, Parikh HA, Roy P, Loewen NA Tags: Exp Eye Res Source Type: research

Crosstalk between TGFβ and Wnt signaling pathways in the human trabecular meshwork.
In this study, we determined whether there is a crosstalk between the TGFβ/Smad pathway and the canonical Wnt pathway using luciferase reporter assays. Lentiviral luciferase reporter vectors for studying the TGFβ/Smad pathway or the canonical Wnt pathway were transduced into primary human non-glaucomatous TM (NTM) cells. Cells were treated with or without a combination of 5 μg/ml TGFβ2 and/or 100 ng/ml Wnt3a recombinant proteins, and luciferase levels were measured using a plate reader. We found that TGFβ2 inhibited Wnt3a-induced canonical Wnt pathway activation, while Wnt3a inhibited TGFβ2-induced TGFβ/Smad pathw...
Source: Experimental Eye Research - April 13, 2016 Category: Opthalmology Authors: Webber HC, Bermudez JY, Sethi A, Clark AF, Mao W Tags: Exp Eye Res Source Type: research

Evaluation of Adenovirus-Mediated Down-Regulation of Connective Tissue Growth Factor on Postoperative Wound Healing After Experimental Glaucoma Surgery.
CONCLUSIONS: Down-regulation of CTGF is effective in inhibiting postoperative scarring in vivo. This suggests that RNAi with CTGF siRNA may potentially pave the road for a novel therapeutic strategy to improve glaucoma surgery results. PMID: 26554857 [PubMed - as supplied by publisher]
Source: Current Eye Research - November 10, 2015 Category: Opthalmology Authors: Lim DH, Kim TE, Kee C Tags: Curr Eye Res Source Type: research

Dexamethasone Increases Cdc42 Expression in Human TM-1 Cells.
Conclusions: DEX increases Cdc42 expression in TM-1. This may represent a potential mechanism of DEX-induced HTM cytoskeletal rearrangement. PMID: 24871483 [PubMed - as supplied by publisher]
Source: Current Eye Research - May 28, 2014 Category: Opthalmology Authors: Qiu X, Wu K, Lin X, Liu Q, Ye Y, Yu M Tags: Curr Eye Res Source Type: research

Activated {alpha}v{beta}3 Integrin Regulates {alpha}v{beta}5 Integrin-Mediated Phagocytosis in Trabecular Meshwork Cells Glaucoma
Conclusions. The αvβ5 integrin-FAK–mediated pathway regulates phagocytosis in TM cells and this pathway is inhibited by activation of αvβ3 integrins. This suggests that changes in integrin expression and activity may be responsible for alterations in phagocytosis observed in steroid induced glaucoma.
Source: Investigative Ophthalmology - July 24, 2013 Category: Opthalmology Authors: Gagen, D., Filla, M. S., Clark, R., Liton, P., Peters, D. M. Tags: Glaucoma Source Type: research