NeuralCipher Research overview
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Abstract Pathological changes in the retina of Parkinson's disease (PD) patients precede diagnostic motor and cognitive symptoms; however, the temporal and sex-specific features of this prodromal pathology remains unclear. To begin to resolve this, we investigated retinal ganglion cell (RGC) structure and optic nerve metabolism in male and female LRRK2 G2019S knock-in mice and wild-type littermates at 4, 8, and 72 weeks, using a combination of Sholl analysis and liquid chromatography–mass spectrometry. Male LRRK2 G2019S mice exhibited RGC structural abnormalities at 4 weeks, whereas comparable changes emerged in females at 8 weeks. Metabolomic profiling revealed distinct age- and sex-dependent alterations, including reduced purine and riboflavin metabolism in young males and increased nicotinate, nicotinamide, and butanoate metabolism in age-matched females. Differing sex-specific metabolic start points and trajectories converged with age, suggesting distinct prodromal mechanisms leading to a shared pathological endpoint. These retinal signatures may facilitate early PD staging and precision medicine.
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