P3.03. INTEGRATING COMPUTATIONAL AND EXPERIMENTAL APPROACHES TO REVEAL TAURINE’S NEUROPROTECTIVE ROLE IN RETINAL ISCHEMIA
Grigoris Agrafiotis1, Dimitris Gkinis1, Maria Avramouli2, Ilias Savvas2, Rodopi Stamatiou3, Stamatia Papoutsopoulou4, Anna Vasilaki1
1 University of Thessaly, Faculty of Medicine, Laboratory of Pharmacology, BIOPOLIS, 41500 Larissa, Greece
2 University of Thessaly, Department of Digital Systems, GAIOPOLIS, 41500 Larissa, Greece
3 University of Thessaly, Faculty of Medicine, Laboratory of Physiology, BIOPOLIS, 41500 Larissa, Greece
4 University of Thessaly, Department of Biochemistry & Biotechnology, BIOPOLIS, 41500 Larissa, Greece
INTRODUCTION: Taurine and its natural derivatives show therapeutic potential in various diseases, but their role in CNS ischemia/reperfusion injury (IRI), including retinal IRI (RIRI), is not fully understood.
AIM(S): This study aimed to integrate computational and in vivo evidence to evaluate the neuroprotective effects of taurine and its derivatives in CNS IRI, using RIRI as a model.
METHOD(S): Network pharmacology and molecular docking were used to identify taurine-related targets and assess binding affinities of taurine and its derivatives (N-acetyltaurine, N-chlorotaurine, N-bromotaurine, glutaurine, taurocholic acid, and tauroursodeoxycholic acid) to key proteins involved in brain IRI. To validate these findings, RIRI was induced in adult male 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. Retinal gliosis, inflammation, and apoptosis were assessed via immunohistochemistry and Western blotting.
RESULTS: Network pharmacology identified 418 taurine-related targets in brain IRI, enriched in apoptosis, immune response, metabolism, and PI3K-Akt pathways. Docking simulations showed strong binding of taurine and its derivatives to key apoptotic proteins (APAF1, cytochrome c, AKT1, SHP2). In vivo, taurine reduced RIRI-induced astrocyte branching and upregulation of GFAP, IL-1β, TNF-α, and cleaved caspase-3, with no effects in sham eyes, indicating injury-specific action.
CONCLUSIONS: Taurine shows neuroprotective potential in RIRI by dampening reactive gliosis, inflammatory cytokine expression, and neuronal apoptosis. Although further validation of the molecular targets of taurine and its derivatives is needed, this study highlights the strength of combining in silico and in vivo approaches to link molecular interactions with neuroprotective effects, underscoring the value of integrated strategies to advance CNS therapeutics.
FINANCIAL SUPPORT: This research was supported by internal funding. No external financial support was received.