INTEGRATING COMPUTATIONAL AND EXPERIMENTAL APPROACHES TO REVEAL TAURINE’S MULTI-TARGET NEUROPROTECTION IN RETINAL ISCHEMIA/REPERFUSION INJURY

CNS ischemia/reperfusion injury (IRI) triggers a complex cascade of apoptosis, glial activation, and inflammation, limiting the efficacy of single-target interventions. Taurine, exerts neuroprotection in several diseases through multimodal, non-canonical mechanisms rather than a single defined target. Naturally occurring taurine derivatives likely further expand this mechanistic repertoire of taurine, yet their molecular targets, signalling pathways, and therapeutic relevance remain largely uncharacterized. To elucidate the molecular basis of taurine’s multi-target neuroprotective effects, we employed network pharmacology and molecular docking to predict taurine-associated targets in CNS IRI. We identified 418 candidate proteins enriched in apoptotic, inflammatory, and survival pathways. Docking suggested preferential interactions of taurine and its natural derivatives with key regulatory nodes, including APAF1, cytochrome c, caspase-3 and AKT1. To validate the computational findings, retinal IRI (RIRI) was induced in 2-month-old Wistar rats by raising intraocular pressure to 110mmHg for 60 minutes; the contralateral eye served as control. Rats received 0.2M taurine in drinking water or remained untreated for 2 weeks before injury and during 24 hours or 7 days of reperfusion. Taurine initiated an early protective response against RIRI-induced astrocyte remodeling and cleaved caspase-3 upregulation, which persisted throughout the post-injury period studied. Taurine attenuated microglial activation and pro-inflammatory cytokine expression while enhancing AKT phosphorylation as early as 24h after reperfusion. Taurine-induced NeuN⁺ ganglion cell survival was evident 7 days after reperfusion. Taurine possibly affords neuroprotection in RIRI by modulating inflammatory and apoptotic responses and engaging AKT-dependent survival signaling, suggesting a multi-target therapeutic potential in CNS ischemia/reperfusion injury.