A LIGHT-INDUCED PATHWAY THROUGH THE GUT-BRAIN AXIS FOR NEUROPROTECTION IN PARKINSON’S DISEASE

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Recent studies indicate the gut-brain axis as a fundamental element in PD. According to our previous research, dim light at night (dLAN) alleviates motor deficits and reduces 𝛼-synuclein aggregation in SNCA p.A53T mice. This study investigates the systemic circuitry mediating these effects. We hypothesized a multi-stage pathway involving retinal input and autonomic relays. To test this, intrinsically photosensitive retinal ganglion cells (ipRGCs) were selectively ablated using saporin-conjugated melanopsin (Melanopsin-SAP). And the sympathetic nervous system was modulated via pharmacological interventions (6-hydroxydopamine) to examine its role in gut-microbiota regulation.
Furthermore, a dual-antibiotic treatment was administered to deplete the gut microbiota, aiming to determine whether microbial integrity is essential for dLAN-induced neuroprotection. Motor performance was assessed through motor behaviour tests to evaluate how sympathetic signaling and microbial integrity contribute to these outcomes. This research establishes a novel "Retinal-Sympathetic-Gut" connection, providing a mechanistic framework for how systemic light signaling across the gut-brain axis may exert neuroprotective effects in PD.