Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Antioxidant and Cytoprotective Potential of Erythropoietin in Mitigating Oxidative Stress-Induced Changes in the Retinal Pigment Epithelium

Version 1 : Received: 9 April 2021 / Approved: 12 April 2021 / Online: 12 April 2021 (09:37:18 CEST)

A peer-reviewed article of this Preprint also exists.

Biswal, M.R.; Wang, Z.; Paulson, R.J.; Uddin, R.R.; Tong, Y.; Zhu, P.; Li, H.; Lewin, A.S. Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from Oxidative Stress in the Retinal Pigment Epithelium. Antioxidants 2021, 10, 842. Biswal, M.R.; Wang, Z.; Paulson, R.J.; Uddin, R.R.; Tong, Y.; Zhu, P.; Li, H.; Lewin, A.S. Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from Oxidative Stress in the Retinal Pigment Epithelium. Antioxidants 2021, 10, 842.

Journal reference: Antioxidants 2021, 10, 842
DOI: 10.3390/antiox10060842

Abstract

Erythropoietin (EPO) protects cells by inhibiting apoptosis, oxidative stress and inflammation in several models of retinal degeneration. In this study, we demonstrate the effects of recombinant Adeno Associated Virus (AAV) vector-mediated delivery of a modified form of erythropoietin (EPO-R76E) in an established mouse model of dry-AMD in which retinal degeneration is induced by RPE oxidative stress. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/Choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific exogenous protein expression. Retinal degeneration was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the progressive retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress as seen in this mouse model.

Keywords

Dry-AMD; oxidative stress; MnSOD; RPE; retinal degeneration; Erythropoietin; gene therapy; Animal model; AAV; ERG

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