Loss of Rod Photoreceptors Reduces the Light Evoked Responses of the Mouse Retinal Pigment Epithelium

Abstract

Purpose: : The retinal pigment epithelium (RPE) supports photoreceptor integrity and function in many ways, and mutations in genes expressed in the RPE underlie a number of human inherited retinal disorders. Because the light evoked responses of the RPE are generated secondary to rod photoreceptor activity, response reduction may reflect a specific change in the response properties of the RPE or simply decreased photoreceptor input. The purpose of this study was to define how the response characteristics of the RPE change in a mouse model of photoreceptor degeneration.

Methods: : To measure RPE function, we used an electroretinogram-based technique (dc-ERG). We studied a slowly progressive mouse model of photoreceptor degeneration (Prph^Rd2/+) at two stages of the degenerative process. We compared changes in the response properties of the dc-ERG to those of the a-wave and slow P3, isolated using the Nyx^nob genetic background. Anatomical structure of the retina and RPE was measured by histological evaluation and immunohistochemistry.

Results: : Nyx^nobPrph^Rd2/+

Conclusions: : Light evoked responses of the RPE in Nyx^nobPrph^Rd2/+ mice were retained at or above the level predicted by a-wave measurements of rod photoreceptor activity. Overall function of the RPE was surprisingly conserved despite loss of photoreceptors and structural damage to the RPE itself. Defining the relationship between photoreceptor degeneration and the response properties of the RPE enables RPE function to be meaningfully evaluated in a broader range of mouse models of human retinal disease.

Keywords: retinal pigment epithelium • degenerations/dystrophies