Syngeneic Mesenchymal Stem Cells Rescue Vision and Vascular Pathology in a Rodent Model of Retinal Degeneration

Abstract

Purpose: : Cell-based therapy has been shown to be effective in slowing down the progression of neurodegenerative diseases in animal models. Bone marrow-derived mesenchymal stem cells (MSCs) present particular advantages for interventional therapy to the eye because they are non-immunogenic, effective at low doses, maintain a stable phenotype and secrete factors known to promote tissue regeneration. Here we assess the potential of MSCs to sustain vision and limit vascular pathology in a rodent model of human retinal disease-the Royal College Surgeon (RCS) rat.

Methods: : MSCs were harvested from the tibiae and femurs of RCS rats at postnatal day (P) 40-50. Adherent cells were collected and cultured, Passages 2-4 were used for the following experiments: MSCs were injected into the subretinal space; MSCs were injected via tail vein; MSCs were delivered into both the subretinal space and tail vein of RCS rats. All recipient animals were syngeneic to donor cells. Animals were tested at several time points by optomotor response and luminance threshold . Photoreceptor rescue and vascular integrity were examined after functional tests.

Results: : Subretinal injection produced substantial rescue morphologically and functionally; single tail vein injection gave photoreceptor rescue across whole retina; combined subretinal and tail injections rescued photoreceptors and vision. There is no obvious vascular pathology in tail vein injected animals up to P120.

Conclusions: : This study demonstrated that MSCs can rescue vision and limit vascular pathology in a rodent model for retinal degeneration. These results suggest that this hypoimmunogenic cells may offer an auto-cell therapeutic approach for retinal diseases.

Keywords: age-related macular degeneration • transplantation • photoreceptors: visual performance