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

Abstract

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 (r² = 0.78) and function (r² = 0.67) and retinal thickness correlated with photoreceptor function (r² = 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.

Keywords:

• Electroretinography
• optical coherence tomography
• optokinetic tracking
• oxidative stress
• retinal degeneration

Acknowledgments

Assistance with OCT analysis techniques was provided by Dr Marco Ruggeri and the Ophthalmic Biophysics Center of University of Miami. We are grateful to William J. Feuer and Joyce Schiffman, Biostatistics Core Facility, Bascom Palmer Eye Institute, for guidance with statistical analysis.

Declaration of interest

The authors declare they have no competing interests.

Funding

This study was supported by a Research to Prevent Blindness Ernest & Elizabeth Althouse Special Scholar Award, the Karl Kirchgessner Foundation, NIH grant RO1 EY017837 and a Fight for Sight Student Fellowship. Institutional support to BPEI was from a Research to Prevent Blindness Unrestricted Grant and an NEI Center Core Grant P30 EY014801. The optokinetic device was designed and built at BPEI’s Ophthalmic Biophysics Center by Victor E. Hernandez MSBME and Jean-Marie Parel PhD with support from the Florida Lions Eye Bank, Karl R. Olsen, MD and Martha E. Hildebrandt, PhD and the Henri and Flore Lesieur Foundation (JMP).

Supplemental material

Supplemental data for this article can be accessed at www.tandfonline.com/icey.