期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 63, 期 8, 页码 -出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.63.8.14
关键词
diabetic macular ischemia; diabetic macular edema; diabetic retinopathy; retinal vein occlusion; Sema3A
资金
- OPEN Health Communications (London, UK) - Boehringer Ingelheim
This study investigated the efficacy of Sema3A neutralizing antibody BI-X and/or anti-VEGF therapy in an RVO mouse model. The results showed that BI-X monotherapy and its combination with anti-VEGF therapy had beneficial effects on intraretinal edema and retinal blood flow. Furthermore, BI-X monotherapy normalized the changes in expression of TNF-alpha and semaphorin-related proteins in the RVO mouse model.
PURPOSE. Semaphorin 3A (Sema3A) is a promising therapeutic target for macular edema in age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion (RVO). Anti-vascular endothelial growth factors (anti-VEGFs) are the current standard of care for many retinal diseases. This study investigated the Sema3A neutralizing antibody BI-X and/or anti-VEGF therapy (aflibercept) in an RVO mouse model. Treatment efficacy was examined and grouped by timing subsequent to the RVO mouse model induction: efficacy against the onset of intraretinal edema 1 day postinduction and protective effects at 7 days postinduction. METHODS. We examined the changes in expression of Sema3A in the retina of an RVO mouse model. In addition, changes in expression of tumor necrosis factor (TNF)-alpha and semaphorin-related proteins (neuropilin-1 and plexin A1) in the retina upon treatment were analyzed by Western blotting. The effects of BI-X and/or aflibercept were evaluated using measures of retinal edema, blood flow, and thinning of the inner nuclear layer. RESULTS. Induction of vein occlusion in the RVO mouse model significantly increased Sema3A expression in the retina, particularly in the inner nuclear layer. BI-X was effective as a monotherapy and in combination with anti-VEGF therapy, demonstrating a beneficial effect on intraretinal edema and retinal blood flow. Moreover, in the RVO mouse model, BI-X monotherapy normalized the changes in expression of TNF-alpha and semaphorinrelated proteins. CONCLUSIONS. These findings support targeting Sema3A to treat intraretinal edema and retinal ischemia.
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