L-DOPA Promotes Post-Treatment Neurovascular and Synaptic Homeostasis in Early Diabetic Retinopathy

Area of Science:

• Ophthalmology
• Neuroscience
• Genetics

Background:

• Diabetic retinopathy (DR) causes retinal dysfunction.
• Levodopa (L-DOPA) has shown a post-treatment protective effect on retinal function in early human DR.
• The biological mechanisms behind L-DOPA's protective effects remain unclear.

Purpose of the Study:

• To investigate the post-treatment functional protection of L-DOPA in a diabetic murine model.
• To identify transcriptional changes in the retina associated with L-DOPA's protective effects.

Main Methods:

• Diabetic mice (streptozotocin-induced) were treated with L-DOPA/carbidopa or vehicle.
• Retinal and visual function were assessed using electroretinography (ERG) and optomotor response (OMR).
• Bulk RNA sequencing and gene co-expression network analysis were performed on retinal tissue.

Main Results:

• L-DOPA treatment protected ERG oscillatory potential timing and OMR performance for at least two weeks post-treatment.
• Flicker-evoked retinal vasodilation improved post-treatment.
• Gene co-expression analysis revealed modules related to synaptic function and cytoskeletal organization correlated with functional protection.

Conclusions:

• L-DOPA restores neurovascular function in early diabetic retinopathy with sustained post-treatment effects.
• The protective effects are associated with transcriptional programs supporting retinal synapse activity and structural integrity.