Photoreceptor Transplantation Rescues Cones by Reversing Cell Damage Morphology

Abstract

Purpose: : We have recently shown that the Rod-derived Cone Viability Factor (RdCVF) delays the loss of function of the cone by exerting a stabilizing effect on the morphology of the cone outer segment in P23H transgenic rats. The purpose of the present study is to extend this observation to the transplantation of normal photoreceptors into the eye of rd1 mouse, the animal model of recessive retinitis pigmentosa (RP).

Methods: : Transplantation was performed using 8-day-old photoreceptor layers isolated by vibratome sectioning from wild type mouse (C57BL/6) retina and grafted into the subretinal space of the rd1 mice (C3H/HeN) at 3 weeks of age. The cone density of the host retinas was measured after labeling with the lectin PNA and using a stereological method 3 weeks after transplantation. We also analyzed the morphology of the cone outer segments.

Results: : The transplantation of normal photoreceptors rescues the cones from the rd1 mouse as shown by an increase of 21% compared to the contralateral untreated retinas (P<0.001), which is consistent with our previous work. We also observed that the transplantation protects the morphology of the cone outer segments from damage linked to the Pde6b mutation. The cones of the treated rd1 eye present small tip areas and longer cone outer segments. In the contralateral untreated rd1 eye, the cone morphology is characterized by an increase in the area of the tip sheath and shortening of cone outer segment, implying that the rd1 cone morphology is altered prior to their death.

Conclusions: : Healthy wild-type photoreceptor transplants can protect cones in rd1 mice by increasing cone number and reversing the damage to the cone morphology. Our observation is consistent with results obtained by transplanting normal photoreceptors into the P23H rat model of autosomal dominant RP or by performing injections of the RdCVF protein in that latter model. Our results suggest that the mechanism underlying the protective effect of the transplantation directly involves the maintenance of a cellular structure essential for cone function.

Keywords: protective mechanisms • retinal degenerations: hereditary • transplantation