Correlation of Preserved Retinal Structure and Function in the RCS Rat

Abstract

Abstract: : Purpose: To determine the relationship between retinal structure and function in the Royal College of Surgeons (RCS) Rat with special reference to transplantation studies. Methods: Six 21 day old RCS rats received subretinal retinal pigment epithelial transplants (three received immortalized human RPE grafts and three received immortalized rat RPE grafts) and four animals received sham injection alone. At four months post transplantation animals underwent collicular visual field mapping and eyes were retrieved for histology. Sample sections were taken at regular intervals (700µm) through the retina (the central ¾ of the retina is taken). Each photoreceptor nucleus was counted across the section in 700µm bins. Thus a numerical gradient across the retina is obtained. This process is repeated for sections at 700µm intervals. A two dimensional histological map of the retina was derived. The logarithmic scales were converted to a decibel scale (ascending, thus greater sensitivity is shown as a peak). Using a bespoke mathematical program (MatLab, version 5.1) a three–dimensional map of both the retinal sensitivity and the histological data was derived. Results: In the dorso–temporal region of the retina there was greater photoreceptor cell preservation that correlated with the maximal area of retinal sensitivity in grafted and sham operated animals. The degree of retinal sensitivity and photoreceptor preservation correlated strongly. Sham–operated animals generated flatter maps. The area of rescue extended far beyond the injection site (up to 3000µm). This analysis demonstrated that the area of photoreceptor rescue varied between 2 and 6 cells thick (90–380 cells/700µm) and covered between 10% and 30% of the total retinal area. In regions distant from the area of graft injection, occasional photoreceptors were encountered in a density similar to that found in unoperated or sham–injected rats. Conclusions: Photoreceptor preservation and retinal sensitivity correlate in the RCS rat model of retinal degeneration and that correlation is predictable.

Keywords: retina • retinal pigment epithelium • transplantation