Epigallocatechin gallate in N-methyl-N-nitrosoureainduced retinitis pigmentosa mouse modelOA

AIM:To investigate the therapeutic efficacy and underlying mechanisms of epigallocatechin gallate(EGCG),a major green tea catechin with potent antioxidant properties,in an N-methyl-N-nitrosourea(MNU)-induced mouse model of retinitis pigmentosa(RP).METHODS:C57BL/6 mice were randomly divided into control(PBS),MNU-induced RP,and MNU+EGCG pretreatment groups.EGCG(50 mg/kg,intraperitoneal)was administered daily for 3 consecutive days prior to a single MNU injection(50 mg/kg).Retinal function was evaluated by scotopic electroretinography(ERG).Retinal structure was assessed using optical coherence tomography(OCT)and hematoxylin-eosin staining,with outer nuclear layer(ONL)thickness measurement.Mechanisms were explored via RNA sequencing,reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)validation of oxidative stress-and inflammation-related genes,and immunohistochemistry for microglial activation,astrocytic gliosis,and apoptosis markers.RESULTS:Compared with the MNU group,EGCG pretreatment significantly preserved scotopic ERG a-wave and b-wave amplitudes(P<0.001).OCT and histological analysis showed that EGCG markedly attenuated MNUinduced thinning of total retina and ONL(P<0.005,P<0.001,respectively).RNA sequencing identified 1147 differentially expressed genes modulated by EGCG,with significant upregulation of antioxidant genes(Nrf2,Sod1,Gpx4,Cat1,Ho-1)and downregulation of pro-inflammatory genes.Immunohistochemistry confirmed that EGCG significantly reduced microglial activation,glial fibrillary acidic protein(GFAP)expression,and cleaved caspase-3-positive cells(P<0.01 to P<0.001).CONCLUSION:EGCG exerts robust neuroprotective effects in MNU-induced RP through enhancement of antioxidant defenses,suppression of neuroinflammation,and preservation of retinal structure and function.These findings suggest EGCG as a promising candidate for adjuvant antioxidant therapy in RP.