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Inhibition of Sema-3A Promotes Cell Migration, Axonal Growth, and Retinal Ganglion Cell Survival.

Authors :
Nitzan A
Corredor-Sanchez M
Galron R
Nahary L
Safrin M
Bruzel M
Moure A
Bonet R
Pérez Y
Bujons J
Vallejo-Yague E
Sacks H
Burnet M
Alfonso I
Messeguer A
Benhar I
Barzilai A
Solomon AS
Source :
Translational vision science & technology [Transl Vis Sci Technol] 2021 Aug 12; Vol. 10 (10), pp. 16.
Publication Year :
2021

Abstract

Purpose: Semaphorin 3A (Sema-3A) is a secreted protein that deflects axons from inappropriate regions and induces neuronal cell death. Intravitreal application of polyclonal antibodies against Sema-3A prevents loss of retinal ganglion cells ensuing from axotomy of optic nerves. This suggested a therapeutic approach for neuroprotection via inhibition of the Sema-3A pathway.<br />Methods: To develop potent and specific Sema-3A antagonists, we isolated monoclonal anti-Sema-3A antibodies from a human antibody phage display library and optimized low-molecular weight Sema-3A signaling inhibitors. The best inhibitors were identified using in vitro scratch assays and semiquantitative repulsion assays.<br />Results: A therapeutic approach for neuroprotection must have a long duration of action. Therefore, antibodies and low-molecular weight inhibitors were formulated in extruded implants to allow controlled and prolonged release. Following release from the implants, Sema-3A inhibitors antagonized Sema-3A effects in scratch and repulsion assays and protected retinal ganglion cells in animal models of optic nerve injury, retinal ischemia, and glaucoma.<br />Conclusions and Translational Relevance: Collectively, our findings indicate that the identified Sema-3A inhibitors should be further evaluated as therapeutic candidates for the treatment of Sema-3A-driven central nervous system degenerative processes.

Details

Language :
English
ISSN :
2164-2591
Volume :
10
Issue :
10
Database :
MEDLINE
Journal :
Translational vision science & technology
Publication Type :
Academic Journal
Accession number :
34817617
Full Text :
https://doi.org/10.1167/tvst.10.10.16