Retinal Transplantation Improves Host Cone Survival in the P23H Rat Model of Retinitis Pigmentosa.

Abstract

Purpose: : We previously demonstrated that transplantation of rods could limit loss of cones which is responsible for main visual handicap in the retinal degeneration mouse model (rd1). Our purpose is to extend this experimental paradigm to another model of retinal degeneration, the P23H transgenic rat.

Methods: : Heterozygote P23H (line 1) rats (78 and 92 days old) were transplanted subretinally in one eye with retinal sheets (2mm x 4mm) obtained from postnatal 8 day Sprague Drawley rats. After various survival times (240–330 days), transplanted retinas were analysed by immunocytochemistry and histology. We quantified the numbers of retinal cones, using a stereological approach to obtain unbiased samples after immunolabeling with peanut agglutinin (PNA) lectin to label cones and anti–opsin Rho–4D2 antibody to label rods.

Results: : In histological sections and on flat mounted retinas demonstrated the persistence of rods within the grafts in the host retinas. In the grafted retinas, cone numbers were higher 2%–85% than that in mocked treated controls. The rescue of cones was an average of 28% for 24 rats examined. Variance analysis and T test showed statistically significance. Meanwhile, the results showed progressive decrease in cone numbers, both in the controls and the grafted retinas over time.

Conclusions: : The present study suggests that the transplantation of retinal sheets, as photoreceptor sheets, can delay the death of cones in a dominant model of rod–cone degeneration. This observation extends the domain of application of transplantation for the treatment in the human Retinitis Pigmentosa.

Keywords: transplantation • photoreceptors • cell survival