An ultrastructural study of the pathology of the retinal pigment epithelium, Bruch's membrane, and the choriocapillaris in the aged Fischer 344 rat

Abstract

Purpose: The neural retinal degeneration in the aging Fischer 344 (F344) rat has been previously characterized. Here we describe the ultrastructural changes that occur in the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in the periphery of the aged Fischer 344 rat.

Methods: F344 eyes from 24-month-old animals (n = 4 animals, 8 eyes) were fixed and embedded for ultrastructural study. Serial mid-sagittal sections were taken from the superior peripheral retinas within 300 microm of the ora serrata. Pathology within the RPE, Bruch's membrane, and choriocapillaris was described.

Results: Progressive changes were seen in the RPE/Bruch's/choriocapillaris complex, increasing anteriorly as the ora serrata was approached. Early pathology of the RPE included increased number of basal infoldings, increased number of phagolysosomes and lipofuscin deposits, attenuation, inclusion of vasculature, vesicle formation, and whirling extensions of the basement membrane into the cytoplasm. Bruch's membrane showed spots of considerable thinning, but most prominent was the nodular thickening. The choriocapillaris was found to have severe endothelial degeneration and transformation to fibrous tissue in the most severely affected regions. Lipofuscin was also found in areas of degenerated choriocapillaris.

Conclusions: Prior work focused on the neural retina, documented photoreceptor cell loss, and showed that Müller cell changes preceded that loss in the periphery of the F344 rat. It is now evident that the pathology in the RPE/Bruch's membrane/choriocapillaris complex may also be a critical component of the overall degenerative process. A possible mechanism for the extensive peripheral retinal degeneration in the F344 is presented.