Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor

EG Faktorovich, RH Steinberg, D Yasumura… - Nature, 1990 - nature.com
EG Faktorovich, RH Steinberg, D Yasumura, MT Matthes, MM LaVail
Nature, 1990nature.com
NUMEROUS inherited retinal degenerations exist in animals and humans, in which
photoreceptors inexplicably degenerate and disappear. In RCS rats with inherited retinal
dystrophy, the mutant gene is expressed in the retinal pigment epithelial (RPE) cell, and
leads to the loss of photoreceptor cells1. Photoreceptors can be rescued from degeneration
if they are juxtaposed to wild-type RPE cells in experimental chimaeras1 or by the
transplantation of RPE cells from normal rats2, 3. In both cases, the rescue effect extends …
Abstract
NUMEROUS inherited retinal degenerations exist in animals and humans, in which photoreceptors inexplicably degenerate and disappear. In RCS rats with inherited retinal dystrophy, the mutant gene is expressed in the retinal pigment epithelial (RPE) cell, and leads to the loss of photoreceptor cells1. Photoreceptors can be rescued from degeneration if they are juxtaposed to wild-type RPE cells in experimental chimaeras1 or by the transplantation of RPE cells from normal rats2, 3. In both cases, the rescue effect extends beyond the immediate boundaries of the normal RPE cells, suggesting trophic action of a diffusible factor(s) from the normal RPE cells. We considered that the fibroblast growth factors, aFGF and bFGF, might have such a trophic role as they are found in the retina4–8 and RPE cells9,10; bFGF acts as a neurotrophic agent after axonal injury in several regions of the central nervous system11–13, and bFGF induces retinal regeneration from developing RPE cells14. Here we report that subretinal injection of bFGF results in extensive rescue of photoreceptors in RCS rats for at least two months after the injection, and that intravitreal injection of bFGF results in even more widespread rescue, across almost the entire retina. The findings demonstrate for the first time that bFGF can act as a survival-promoting neurotrophic factor in a hereditary neuronal degeneration of the central nervous system.
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