Defining the Relationships Among Retinal Function, Layer Thickness and Visual Behavior During Oxidative Stress-Induced Retinal Degeneration

PURPOSE: The purpose of this study was to identify how changes in retinal structure and function correlate with visual deficits during increasing amounts of retinal degeneration. MATERIALS AND METHODS: Retinal degeneration was induced in adult mice by subretinal injections of paraquat (PQ) (0.2-1 mM). Retinal anatomy and photoreceptor layer thickness were quantified by histology and optical coherence tomography (OCT), retinal function was measured using electroretinography (ERG), and visual behavior were measured by optokinetic tracking, at 1 to 3 week post-injury. RESULTS: Photoreceptor layer structure, function and visual behavior declined at a linear rate over time following PQ-induced degeneration, with the correlations between outcome measures being lowest at mild injury levels and increasing with injury severity. Overall reductions in visual acuity were highly correlated with declines in retinal thickness (r(2) = 0.78) and function (r(2) = 0.67) and retinal thickness correlated with photoreceptor function (r(2) = 0.72). ERG a-wave scotopic amplitudes showed a stronger correspondence to retinal structure and visual behavior than b-waves. CONCLUSIONS: Measurements of photoreceptor loss at the structural and functional levels showed good correspondence with degeneration-associated changes in visual behavior after oxidative stress injury. The results provide new insight about the relative kinetics of measurements of retinal degeneration induced by oxidative stress, which could guide the choice of optimal outcome measurements for other retinal diseases.