L-DOPA treatment promotes sustained neurovascular and synaptic homeostasis in the diabetic retina.

While previous work has shown a sustained protective effect of levodopa (L-DOPA) on retinal function in early-stage diabetic retinopathy (DR) in humans, its underlying biology is unknown. Using noninvasive measures in diabetic mice, we found L-DOPA protects retinal neurovascular function as measured by oscillatory potential timing and flicker-evoked retinal vasodilation, as well as visual behavior, for at least two weeks past treatment end. Assessing changes in retinal gene expression, differentially expressed genes were broadly comparable between diabetic mice experiencing washout of L-DOPA versus continued L-DOPA treatment, with gene co-expression network analysis identifying distinct modules across L-DOPA-treated diabetic mice associated with synaptic function and cytoskeletal organization that correlated with functional protection. Together, these findings demonstrate that L-DOPA restores and sustains retinal neurovascular function in early DR and links this protection to transcriptional programs supporting synapse activity and structural integrity.