Efficacy of an Anti-Semaphorin 3A Neutralizing Antibody in a Male Experimental Retinal Vein Occlusion Mouse Model.

Abstract

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)-α 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-α and semaphorin-related proteins.

Conclusions:

These findings support targeting Sema3A to treat intraretinal edema and retinal ischemia.

• Authors: Shinsuke Nakamura, Anri Nishinaka, Yae Hidaka, Masamitsu Shimazawa, Leo Thomas, Remko A Bakker, Hideaki Hara
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 63 Issue 8 Pg. 14 (07 08 2022) ISSN: 1552-5783 [Electronic] United States
• PMID: 35822950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Neutralizing
• Semaphorin-3A

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Antibodies, Neutralizing (pharmacology, therapeutic use)
• Disease Models, Animal
• Intravitreal Injections
• Macular Edema (drug therapy)
• Male
• Mice
• Retina (pathology)
• Retinal Diseases (pathology)
• Retinal Vein Occlusion (metabolism)
• Semaphorin-3A (metabolism)