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Retinal and choroidal angiogenesis: a review of new targets.

ABSTRACT: Retinal and choroidal neovascularization are a major cause of significant visual impairment, worldwide. Understanding the various factors involved in the accompanying physiopathology is vital for development of novel treatments, and most important, for preserving patient vision. The intraocular use of anti-vascular endothelial growth factor therapeutics has improved management of the retinal and choroidal neovascularization but some patients do not respond, suggesting other vascular mediators may also contribute to ocular angiogenesis. Several recent studies examined possible new targets for future anti-angiogenic therapies. Potential targets of retinal and choroidal neovascularization therapy include members of the platelet-derived growth factor family, vascular endothelial growth factor sub-family, epidermal growth factor family, fibroblast growth factor family, transforming growth factor-? superfamily (TGF-?1, activins, follistatin and bone morphogenetic proteins), angiopoietin-like family, galectins family, integrin superfamily, as well as pigment epithelium derived factor, hepatocyte growth factor, angiopoietins, endothelins, hypoxia-inducible factors, insulin-like growth factors, cytokines, matrix metalloproteinases and their inhibitors and glycosylation proteins. This review highlights current antiangiogenic therapies under development, and discusses future retinal and choroidal pro- and anti-angiogenic targets as wells as the importance of developing of new drugs.

SUBMITTER: Cabral T

PROVIDER: S-EPMC5563895 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Retinal and choroidal angiogenesis: a review of new targets.

Cabral Thiago T Mello Luiz Guilherme M LGM Lima Luiz H LH Polido Júlia J Regatieri Caio V CV Belfort Rubens R Mahajan Vinit B VB

International journal of retina and vitreous 20170821

Retinal and choroidal neovascularization are a major cause of significant visual impairment, worldwide. Understanding the various factors involved in the accompanying physiopathology is vital for development of novel treatments, and most important, for preserving patient vision. The intraocular use of anti-vascular endothelial growth factor therapeutics has improved management of the retinal and choroidal neovascularization but some patients do not respond, suggesting other vascular mediators ma ...[more]

PMID: 28835854

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Project description:Background: To identify and functionally annotate cell type-specific gene expression in the human retinal pigment epithelium (RPE), a key tissue involved in age-related macular degeneration and retinitis pigmentosa. Methodology: RPE, photoreceptor and choroidal cells were isolated from selected freshly frozen healthy human donor eyes using laser microdissection. RNA isolation, amplification and hybridization to 44k microarrays was carried out according to Agilent specifications. Bioinformatics was carried out using Rosetta Resolver, David and Ingenuity software. Principal Findings: Our previous 22k analysis of the RPE transcriptome showed that the RPE has high levels of protein synthesis, strong energy demands, is exposed to high levels of oxidative stress and a variable degree of inflammation. We currently use a complementary new strategy aimed at the identification and functional annotation of RPE-specific expressed transcripts. This strategy takes advantage of the multilayered cellular structure of the retina and overcomes a number of limitations of previous studies. In triplicate, we compared the transcriptomes of RPE, photoreceptor and choroidal cells and we deduced RPE specific expression. We identified at least 114 entries with RPE-specific gene expression. Thirty-nine of these 114 genes also show high expression in the RPE, comparison with the literature showed that 85% of these 39 were previously identified to be expressed in the RPE. In the group of 114 RPE specific genes there was an overrepresentation of genes involved in (membrane) transport, vision and ophthalmic disease. More fundamentally, we found RPE-specific involvement in the RAR-activation, retinol metabolism and GABA receptor signaling pathways. Conclusions: In this study we provide a further specification and understanding of the RPE transcriptome by identifying and analyzing genes that are specifically expressed in the RPE. Six RPE samples, three phot samples, three choroid samples

Project description:Purpose We performed a systematic review and meta-analysis to examine the microvascular alterations in non-ocular Behcet’s disease (BD) using optical coherence tomography angiography (OCTA). Methods A comprehensive search was performed in Pubmed, Embase and Cochrane databases for eligible studies from inception to February 2022. Detailed clinical demographics were extracted from each study by two independent reviewers. The weighted mean difference (WMD) and 95% confidence intervals (CI) were used to compare the OCTA parameters between non-ocular BD and healthy controls. Stata 12.0 was adopted to conduct statistical analyses. Results Ten cross-sectional studies involving 386 eyes in non-ocular BD and 418 eyes in healthy volunteers were ultimately included in the present analysis. When considering superficial capillary plexus (SCP) and deep capillary plexus (DCP), no significant differences of vessel densities in the whole enface image, fovea and perifovea were evaluated between two groups. Significantly reduced parafoveal vessel density of SCP was observed in non-ocular BD in comparison with healthy group (WMD = −1.33, 95%CI: −1.78, −0.89; I2 = 0.6%), while slightly decreased parafoveal vessel density was assessed in DCP (WMD = −1.47, 95%CI: −3.30, 0.35; I2 = 89.3%). Significantly increasing foveal avascular zone (FAZ) area was observed in non-ocular BD when compared to healthy controls (WMD = 0.11, 95%CI: 0.03, 0.19; I2 = 95.3%). There was no significant difference in flow area of choriocapillaris between non-ocular BD and control group (WMD = 0.06, 95%CI: −0.19, 0.32; I2 = 0%). Conclusion Based on current analysis, our results demonstrated significantly lower parafoveal vessel density of SCP and lager FAZ area in full vasculature in non-ocular BD. The retinal microvascular alterations appear before the emergence of ocular manifestations. Systematic Trial Registration [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021244856].

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Retinal and choroidal angiogenesis: a review of new targets.

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Retinal and choroidal angiogenesis: a review of new targets.

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