Abstract
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 MNU-induced 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.