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

Autor:	Nitzan A; Department of Neurobiology, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Corredor-Sanchez M; Department of Biological Chemistry, Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain., Galron R; Department of Neurobiology, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Nahary L; The Shmunis School of Biomedicine and Cancer Research, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Safrin M; Goldschleger Eye Research Institute, Sheba Medical Center, Tel Aviv University Tel Aviv, Israel., Bruzel M; Goldschleger Eye Research Institute, Sheba Medical Center, Tel Aviv University Tel Aviv, Israel., Moure A; Department of Biological Chemistry, Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain., Bonet R; Department of Biological Chemistry, Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain., Pérez Y; Department of Biological Chemistry, Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain., Bujons J; Department of Biological Chemistry, Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain., Vallejo-Yague E; Synovo GmbH, Tübingen, Germany., Sacks H; Nicast Ltd., Global Park, Lod, Israel., Burnet M; Synovo GmbH, Tübingen, Germany., Alfonso I; Department of Biological Chemistry, Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain., Messeguer A; Department of Biological Chemistry, Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain., Benhar I; The Shmunis School of Biomedicine and Cancer Research, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Barzilai A; Department of Neurobiology, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Solomon AS; Goldschleger Eye Research Institute, Sheba Medical Center, Tel Aviv University Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Jazyk:	angličtina
Zdroj:	Translational vision science & technology [Transl Vis Sci Technol] 2021 Aug 12; Vol. 10 (10), pp. 16.
DOI:	10.1167/tvst.10.10.16
Abstrakt:	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. 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. 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. 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.
Databáze:	MEDLINE
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