Initiation of L-DOPA Treatment After Detection of Diabetes-Induced Retinal Dysfunction Reverses Retinopathy and Provides Neuroprotection in Rats

• Authors: Kyle Chesler, Emory University; Cara Motz, Emory University; Harrison Vo, Atlanta VA Healthcare System; Amber Douglass, Atlanta VA Healthcare System,; Rachael Allen, Emory University; Andrew Feola, Emory University; Machelle Pardue, Emory University
• Journal Title: TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
• Volume: Volume 10, Number 4
• Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC | 2021-04-01, Pages 8-8
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1167/tvst.10.4.8
• Subjects: Engineering, Biomedical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Ophthalmology; diabetes; retina; dopamine; retinopathy; neuroprotection; VASCULAR-PERMEABILITY; PARKINSONS-DISEASE; VISUAL DYSFUNCTION; MODEL; LEVODOPA; DEFICITS; ELECTRORETINOGRAM; THERAPY; DELAYS; STRIATUM

Abstract

Purpose: L-DOPA treatment initiated at the start of hyperglycemia preserves retinal and visual function in diabetic rats. Here, we investigated a more clinically relevant treatment strategy in which retinal and visual dysfunction designated the beginning of the therapeutic window for L-DOPA treatment. Methods: Spatial frequency thresholds using optomotor response and oscillatory potential (OP) delays using electroretinograms were compared at baseline, 3, 6, and 10 weeks after streptozotocin (STZ) between diabetic and control rats. L-DOPA/carbidopa treatment (DOPA) or vehicle was delivered orally 5 days per week beginning at 3 weeks after STZ, when significant retinal and visual deficits were measured. At 10 weeks after STZ, retinas were collected to measure L-DOPA, dopamine, and 3,4-dihydroxyphenylacetic acid (DOPAC) levels using high-performance liquid chromatography. Results: Spatial frequency thresholds decreased at 6 weeks in diabetic vehicle rats (28%), whereas diabetic DOPA rats had stable thresholds (<1%) that maintained to 10 weeks, creating significantly higher thresholds compared with diabetic vehicle rats (P < 0.0001). OP2 implicit times in response to dim, rod-driven stimuli were decreased in diabetic compared with control rats (3 weeks, P < 0.0001; 10 weeks, P < 0.01). With L-DOPA treatment, OP2 implicit times recovered in diabetic rats to be indistinguishable from control rats by 10 weeks after STZ. Rats treated with L-DOPA showed significantly increased retinal L-DOPA (P < 0.001) and dopamine levels (P < 0.05). Conclusions: L-DOPA treatment started after the detection of retinal and visual dysfunction showed protective effects in diabetic rats. Translational Relevance: Early retinal functional deficits induced by diabetes can be used to identify an earlier therapeutic window for L-DOPA treatment which protects from further vision loss and restores retinal function.