Potential of Retinal Stem Cells in the Treatment of Diabetic Retinopathy

Abstract

Purpose:: Diabetic retinopathy is one of the leading causes of blindness. In diabetic patients, sustained high level of glucose leads to the breakdown of the blood-retinal barrier, leading to increased vascular permeability, macular edema and ischemia in the retina. This further induces neovascularization and bleeding in the eye and results in the loss of retinal neurons and blindness. Currently there is no effective treatment for preserving visual acuity in these patients. Recently, adult retinal stem cells (RSCs) have been discovered in the adult mammalian eye, reinvigorating the regenerative strategy in the treatment of retinal degeneration. We found that pigment epithelium derived factor (PEDF), a potent inhibitor of angiogenesis and vasopermeability, is expressed in RSC spheres. We hypothesize that transplantation of RSCs may prevent or slow down the vascular damage and neovascularization as well as provide new retinal cells to replenish the lost retinal neurons. The purpose of this study was to explore these potentials.

Methods:: We used the Ins2^Akita/wt mice, in which a dominant mutation in the insulin-2 gene induces diabetes and diabetic retinopathy. We isolated RSCs from adult Tg(ActbEYFP) mice, in which Enhanced Yellow Fluorescent Protein (EYFP) is expressed in all cells. We injected EYFP-labeled RSC sphere cells (10⁴/0.5 µl) intravitreally into the right eyes of Ins2^Akita/wt pups and their wild type littermates at postnatal day 1-6. For control, the left eyes were injected with saline solution. The transplanted eyes were collected 1 week, 1 month and 3 months after injection. The survival, integration and differentiation of the transplanted RSCs, as well as the morphology, vascular permeability and microglial activity of the host retinas are to be studied.

Results:: Our preliminary studies showed that RSC sphere cells were present in the transplanted eyes of both the Ins2^Akita/wt mice and their wild type littermates at all three time points and they mostly reside in the subretinal space. Further characterization of the integration and differentiation of the transplanted cells and study on the progression of diabetic retinopathy of the transplanted host retina are currently under way.

Conclusions:: Adult RSC sphere cells are able to survive in the host eyes for up to 3 months and are capable of migrating through the retina. Our ongoing characterization of the transplanted eyes will provide more insight on the potential of RSCs in the prevention or treatment of diabetic retinopathy.

Keywords: retina • diabetic retinopathy • transplantation