Synergistic protection from retinal degeneration by Combined stem cell therapies

Abstract

Purpose : Neural progenitor cells (NPCs) have been shown effective in preserving both photoreceptors and visual function after subretinal injection into rodent models for retinal degeneration. Our recent studies revealed that a subretinal injection of MSC (MSC^SRI) combined with intravenous injection of MSC (MSC^IV) into the Royal College of Surgeons (RCS) rats with inherited retinal degeneration offers synergistic protection from retinal degeneration and vision loss. The purpose of this study was to investigate clinical relevant NPCs combined with MSC^IV as adjuvant therapy for preserving vision in the RCS rat model for retinal degeneration.

Methods : NPC^SRI were performed into the RCS rats at postnatal day (P) 21-23, followed by MSC^IV on the next day. Blood samples were collected at the several time points after the treatments. Visual function was examined at P60 and P90. Retinas were collected for histology and proteomic analysis.

Results : Combined NPC^SRI and MSC^IV enhanced visual function as tested by optokinetic response (OKR) and electroretinography (ERG) compared with NPC^SRI alone. Further examination on NPC^SRI indicated the combined treatments promoted survival of NPC^SRI. Proteomic analysis revealed that quality of photoreceptors, function of retina and engraftment of cells related pathway were up-regulated with MSC^IV supplementary; apoptosis of neurons, generation of reactive oxygen species related pathway were down regulated.

Conclusions : Combined stem/progenitor treatments offer enhanced protection from retinal degeneration and vision loss. MSC^IV as supporting therapy to modulate host immune response and improve overall host microenvironment may have broader application to the regenerative medicine.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.