Mechanism of Stem Cells in Rescuing Vision in a Rodent Model of Retinal Degeneration

Abstract

Purpose: : Cell-based therapy has been shown to be effective in slowing down the progression of retinal degeneration in animal models. However, the molecular mechanisms underlying vision rescue are unclear. It is likely that both the injected cells and the host retina undergo molecular changes post-transplant. Here we study changes in expression of growth factor genes by human progenitor cells before and after injection into the eye in a rodent model of retinal degeneration, as well as changes in gene expression in host retinal neurons following the injection.

Methods: : Human forebrain derived progenitor cells (hNPC^ctx) were injected into the subretinal space of RCS rats at postnatal day (P) 21-23. The efficacy of injected cells was examined by measurements of visual acuity. Retinal tissues and injected hNPC^ctx were collected at P35, P60 and P90 using laser capture microdissection (LCM). RNA from hNPC^ctx and retinal tissues were isolated and examined for expression of trophic factors by polymerase chain reaction and immunohistochemistry.

Results: : Subretinal injection of hNPC^ctx produced substantial rescue morphologically and functionally. Trophic factors released by human donor cells, including IGF and BDNF, were detected both in vitro and in vivo. However, at P90, BDNF was no longer detected. The host retina expressed Apolipoprotein E in areas close to the donor cell distribution.

Conclusions: : This study demonstrates that vision rescue by injected hNPC^ctx is correlated with the expression of trophic factors released by both donor cells and the host retina. The cellular localization of these factors in the host retina is under investigation.

Keywords: retinal degenerations: cell biology • gene/expression • transplantation