Open AccessInitiation of L-DOPA Treatment After Detection of Diabetes-Induced Retinal Dysfunction Reverses Retinopathy and Provides Neuroprotection in Rats
Author(s) -
Kyle Chesler,
Cara Motz,
Harrison Vo,
Amber Douglass,
Rachael S Allen,
Andrew Feola,
Machelle T. Pardue
Publication year - 2021
Publication title -
translational vision science and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 21
ISSN - 2164-2591
DOI - 10.1167/tvst.10.4.8
Subject(s) - neuroprotection , diabetic retinopathy , medicine , retinal , diabetes mellitus , retinopathy , ophthalmology , pharmacology , neuroscience , endocrinology , biology
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.