# Early retinal synaptic dysfunction and proteomic remodeling precede neurodegeneration in a Parkinson’s disease model

## TL;DR

This study shows that retinal changes happen early in a Parkinson’s disease model, before neurodegeneration, and reveals molecular changes that could help detect the disease earlier.

## Contribution

The study identifies early retinal synaptic dysfunction and proteomic changes in a Parkinson’s disease model preceding neurodegeneration.

## Key findings

- Early retinal dysfunction was detected via reduced scotopic oscillatory potential amplitudes in mice.
- Proteomic profiling revealed stage-dependent alterations involving α-synuclein and oxidative stress markers.
- Network analysis showed progression from α-synuclein disruption to inflammation and metabolic changes.

## Abstract

Parkinson’s disease (PD) affects motor and non-motor systems; however, 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 a reduction in scotopic oscillatory potential amplitudes on electroretinography. Optical coherence tomography showed early thinning of the retinal nerve fiber layer/ganglion cell layer, and photoreceptor layer, accompanied by thickening of the inner plexiform layer. Phosphorylated α-synuclein accumulation, increased glial fibrillary acidic protein, and loss of the ribbon synapse protein CtBP2 were observed. Proteomic profiling revealed stage-dependent alterations involving α-synuclein, oxidative stress markers, and crystallins. Network analysis showed progression from α-synuclein-associated disruption to inflammation and metabolic remodeling. These results highlight retinal alterations as early indicators of PD neurodegeneration and provide mechanistic insights into the molecular events that precede neuronal loss.