Discrepant Anatomical, Electrophysiolgical, and Behavioral Profiles of Retinal Degeneration in Rat Models of Retinal Degenerative Disease

Abstract

Purpose:: Behavioral measures of vision, electroretinogram (ERG) recordings, and photoreceptor number based on outer nuclear layer (ONL) quantification do not always correlate well in retinal degeneration (RD) models. The purpose of this study was to directly evaluate the degree of correspondence between behavioral, physiological, and anatomical measures of visual system function in rat models of human RD diseases.

Methods:: Spatial frequency thresholds of the optokinetic response (OKR), ERGs and ONL thickness were measured longitudinally from eye opening in dystrophic Royal College of Surgeons (RCS) and mutant rhodopsin transgenic (P23H lines 1 and 3, and S334ter lines 3, 4 and 9) rats.

Results:: OKR thresholds were measurable in all groups and the rate of visual degeneration varied dramatically with genotype. ERG scotopic b-waves were measurable in all but one group (S334ter-3), and in most cases their amplitudes followed a similar degenerative progression as ONL thickness within a given line of rats. The profile of degeneration in vision, however, frequently did not correspond with the degenerative profiles of ERG and ONL measurements: Measurable vision persisted in some groups after the ERG was lost, and vision degenerated rapidly in some with little evidence of ONL disruption.

Conclusions:: Visual performance is not predicted by ERG amplitudes or ONL quantification in all forms or rates of RD in rats. These findings suggest that clinically relevant behavioral measures of vision must be included in studies directed at evaluating potential therapies for retinal degenerative disease.

Keywords: visual acuity • retinal degenerations: cell biology • electroretinography: non-clinical