RETINAL DOPAMINERGIC DEPLETION IN MICE REVEALS VISUAL IMPAIRMENT AND A MELANOPSIN-DEPENDENT MODULATION OF RETINAL NEURODEGENERATION

Aims: Parkinson’s disease (PD) involves the progressive degeneration of dopaminergic neurons, a process that also affects the retina, where dopaminergic amacrine cells (DACs) play a key role in visual processing. Since PD patients often show visual disturbances, understanding retinal dopaminergic loss is crucial. In this work, we used intravitreal administration of 6-hydroxydopamine (6-OHDA), a selective dopaminergic neurotoxin, to model this degeneration and evaluate its consequences on retinal physiology and visual performance. Methods: 6-OHDA was injected intravitreally into wild-type (WT) and melanopsin-deficient (Opn4-/-) mice. Visual behavior and electrophysiological responses were recorded before treatment and days afterward. Dopamine content and related metabolites were quantified by high-performance liquid chromatography, while protein expression was assessed by western blotting and immunohistochemistry. A reproducible and modular statistical analysis workflow was applied, integrating group imputation, outlier control, normality and homoscedasticity assessment, adaptive inferential tests and effect size estimation. Results: Treated animals exhibited reduced visual acuity and diminished electrophysiological response at 20 days, persisting over time. Biochemical analyses revealed a decline in dopamine, together with reduced dopamine-related proteins expression and altered connections between DACs and Starburst Amacrine Cells (SACs). Although also altered, a difference in the results was found in melanopsin-lacking Opn4⁻/⁻mice. Conclusions: Intravitreal 6-OHDA reproduces key retinal alterations associated with dopaminergic degeneration, offering a reliable model to study visual impairments linked to Parkinson’s disease. The findings in Opn4⁻/⁻ mice highlight the interaction between melanopsin and dopaminergic pathways in maintaining retinal function.