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Shaomei Wang, Bin Lu, Sergey Girman, Muhammad U. Jawad, David M. Gamm, Catherine W. Morgans, Brandon Shelley, Clive Svendsen; Combined Local and Global Cellular Therapies for Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2584.
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Cell-based therapy has been shown to be effective in limiting retinal degeneration in multiple animal models. Prior to extensive photoreceptor loss, preservation of host retinal anatomy and function is the primary therapeutic goal. Our previous studies have shown that human neural progenitor cells derived from prenatal cortex (hNPCctx) can survive, migrate and integrate into the host retina and offer significant preservation of vision. We have also shown that bone marrow derived mesenchymal stem cells (MSCs) can exert extensive protection of photoreceptors when delivered systemically. Here, we study whether combined subretinal (hNPCctx) and systemic (MSCs) delivery enhance the efficacy on preserving vision in the Royal College Surgeon (RCS) rats, a well-studied model for retinal degeneration. We hypothesize that hNPCctx will offer great local preservation of vision, while MSCs will foster a global environment that is favorable for hNPCctx survival and integration.
hNPCctx, 30,000 cells/eye were injected into the subretinal space of the Royal College Surgeon (RCS) rats at P21, one million MSCs isolated from RCS rats with our published protocol, were injected intravenously into the RCS rats at P22. Control animals received PBS subretinal injection and untreated. All Animals were maintained under immunosuppression (cyclosporine A in drinking water) throughout the experimental period. Animals were examined at several time points afterward.
Combined treatments showed an extensive preservation of photoreceptors and visual function. There were 8-10 layers of photoreceptors in treated eyes compared with a single layer of photoreceptors in the control groups. Visual function, tested by optokinetic responses (OKR) and luminance threshold recordings from the superior colliculus, were also extensively preserved compared with controls
Combined hNPCctx and MSC cellular therapies offer extensive preservation of both photoreceptors and visual function. hNPCctx and MSCs have been widely used in research and clinical trials. This new approach may offer the realistic likelihood of translation into the clinic to treat retinal degeneration.
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