The effect of S‐allyl L‐cysteine on retinal ischaemia: The role of MCP ‐1 and PKM2

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Aims/Purpose: Retinal ischaemia plays an important role in vision threatening retinal ischaemic disorders, such as central/branch RAO, nvAMD and normal tension glaucoma. The aim of this study was to determine the effects of S‐allyl L‐cysteine (SAC) and its underlying mechanism. Methods: Porcine RPE (pRPE) cells were extracted from adult pig eyes and maintained in DMEM containing 10% FBS, 100 U/mL penicillin and 100 mg/mL streptomycin in a humidified atmosphere of 95% air and 5% CO2 at 37°C. Cell viability was evaluated by via a haemocytometre under an optical microscope. H2O2 (500 μM) was added for 24 h to stimulate an oxidative stress and SAC or vehicle was added to some groups of the cultured pRPE cells 15 min before adding H2O2. Besides, high intraocular pressure (HIOP)‐induced retinal ischaemia was established by raising IOP to 120 mmHg for 60 min in a Wistar rat eye. This ischaemic insult is followed by 7 days of reperfusion. Whether and how ‘SAC’ is able to prevent retinal ischaemic injury were assessed by electrophysiology, fluorogold‐labeling and ELISA/western blot. Results: H2O2 (500 μM) stimulated free radical formation in cultured pRPE cells and significantly reduced the cell viability. This harmful effect was dose‐dependently (25/50 μM) and significantly (100 μM) ameliorated by pretreatment with SAC. Moreover, post‐administration of mega‐dose SAC (I/R + SAC 9 μg/kg/day ≈ 0.18 mg/0.2 Kg rat) counteracted the ischaemia‐induced decrease in the ERG b‐wave and reduction in the RGC cell number in the rat retina. This study supports an antioxidative role for SAC. Through the ELISA/western blot, SAC (100 μM) appears to protect against H2O2‐induced oxidative stress via the downregulation of ischaemia‐related factor PKM2 and inflammatory biomarker MCP‐1. Conclusions: SAC might protect against retinal ischaemia by antioxidation, anti‐ischaemia and anti‐inflammation (downregulating PKM2 and MCP‐1). References 1. Chao, et al. S‐Allyl L‐Cysteine Protects the Retina against Kainate Excitotoxicity in the Rat. The Am J Chin Med, 42:693–708, 2014. 2. Chao, et al. Fortified S‐Allyl L‐Cysteine: Animal Safety, Effect on Retinal Ischemia, and Role of Wnt in the Underlying Therapeutic Mechanism. Evid Based Complement Alternat Med, 2020:1–12, 2020.

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