Retinal ischemia: Therapeutic effects and mechanisms of paeoniflorin

Aims/Purpose: Retinal ischemia‐associated ocular disorders are vision threatening. The aim of the present study is to assess the potential of paeoniflorin in alleviating retinal ischemic injury and to uncover the mechanisms involved.Methods: Cultured retinal cells were subjected to oxygen glucose deprivation (OGD; N2/CO2/O2: 95 %/5 %/1 %) with pre‐OGD (1h) administration of paeoniflorin (0.25/0.5 mM). The cell viability were evaluated by MTT assay.High intraocular pressure‐induced retinal ischemia (I) was established by raising IOP to 120 mmHg for 60 minutes followed by reperfusion (R) for 7 days in an ischemic eye in a Wistar rat. The physiological effects of the retina were evaluated by electrophysiology and fluorogold retrograde labelling RGCs. The protein levels of angiopoietin, pyruvate kinase M2 (PKM2), Wnt3a and β‐catenin were assessed by Western blotting.Results: Pre‐ischemic administration of paeoniflorin dose‐dependently (less effect at 0.25 mM) and significantly (p < 0.05; 0.5 mM) alleviated OGD induced significant (p < 0.001) decrease in RGC‐5 cell viability. Furthermore, pre‐ischemic administration of paeoniflorin dose‐dependently (less effect at 0.25 mM) and significantly (p < 0.05/p < 0.001; 0.5 mM) attenuated ischemia‐induced significant (p < 0.001/ p < 0.05) reduction in ERG b‐wave amplitude/RGC cell number.Compared to eyes treated with vehicle, paeoniflorin (p < 0.05/p < 0.01/p < 0.05; 0.5 mM) seemed to protect against retinal ischemia by regulating angiopoietin, β‐catenin, WNT and PKM2 expression.Conclusions: The treatment with paeoniflorin is able to effectively reduce retinal ischemia by affecting angiopoietin, β‐catenin, WNT and PKM2 biomarkers.References Windsor Wen‐Jin Chao, Howard Wen‐Haur Chao, Hung‐Fu Lee, Hsiao‐Ming Chao. The Effect of S‐Allyl L‐Cysteine on Retinal Ischemia: The Contributions of MCP‐1 and PKM2 in the Underlying Medicinal Properties. Int J Mol Sci. 2024 Jan 22;25(2):1349. Chao HM, Osborne NN. Topically applied clonidine protects the rat retina from ischaemia/reperfusion by stimulating alpha(2)‐adrenoceptors and not by an action on imidazoline receptors. Brain Res. 2001 Jun 15;904(1):126‐36.