Sustained Protective Effects of L-DOPA Treatment in Mice with Diabetes-Induced Retinal Dysfunction
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Savant, Nikita Uday
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Abstract
Diabetic retinopathy (DR), a highly prevalent complication of diabetes mellitus (DM), is the leading cause of blindness in working-age adults in the U.S. Although a clinical diagnosis of DR relies on the presence of vascular abnormalities within the eye, our lab has previously found that visual deficits stemming from DM may appear prior to any vascular changes. We have seen that starting levodopa (L-DOPA) treatment upon the detection of visual dysfunction improves visual and retinal function and that retinal improvements in particular are maintained even after a washout period post-treatment in humans. However, the temporal relationship between diabetes onset, early DR, and L-DOPA treatment has not yet been clearly established, and the washout period in the human study only spanned 2 weeks. Thus, we aim to confirm the maintenance of visual protection after a longer period of washout in rodents so that future studies may examine the mechanisms behind this observation.
Similar to previous studies, we expect to see protection against visual decline in the levodopa-treated diabetic mice which will be maintained even after a washout period. In this study, we induced DM in mice and randomized them to L-DOPA and vehicle treatment subgroups to assess changes in their visual acuity and visually evoked responses over the course of the study.
During the washout period, we saw lasting protective effects in visual acuity during the early phases of DR. There was no statistically significant difference in contrast sensitivity between vehicle and L-DOPA-treated diabetic animals, though we did see protective trends in contrast sensitivity. Additionally, we saw some protective trends from L-DOPA treatment in visually evoked responses during the washout at dim light levels within the early phases of DR. These trends should be further evaluated in future studies to assess the strength of the effect. We conclude that L-DOPA/carbidopa treatment may provide some protection against visual dysfunction in early-stage DR, implying that L-DOPA treatment mediates some longer-lasting changes which allow its effects to last beyond its short half-life in the body.
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