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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054623 | PMC |
| http://dx.doi.org/10.1167/tvst.10.4.8 | DOI Listing |
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