Parkinson’s disease (PD) affects motor and non-motor systems, but retinal changes and their molecular basis are not well understood. Using a transgenic mouse model overexpressing A53T-mutant human α-synuclein, we examined retinal function, structure, and proteomics at 6 and 16 months. Early retinal dysfunction was detected by reduced ERG b-wave amplitudes and oscillatory potentials, preceding photoreceptor loss. OCT showed thinning of ganglion cell and photoreceptor layers with thickening of the inner plexiform layer. Phosphorylated α-synuclein and increased GFAP indicated early neuroinflammation. Proteomic profiling revealed stage-dependent alterations involving α-synuclein, oxidative stress markers, and crystallins. Network analysis showed a progression from α-synuclein-related changes to immune-metabolic remodeling. These results highlight retinal alterations as early indicators of PD neurodegeneration, offering new insights into disease mechanisms.