Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy  

作　　者：Samuel Abokyi Dennis Yan-yin Tse 

机构地区：[1]School of Optometry,The Hong Kong Polytechnic University,Kowloon,Hong Kong Special Administrative Region,China [2]Research Center for SHARP Vision,The Hong Kong Polytechnic University,Kowloon,Hong Kong Special Administrative Region,China [3]Center for Eye and Vision Research,Sha Tin,Hong Kong Special Administrative Region,China

出　　处：《Neural Regeneration Research》2025年第2期366-377,共12页中国神经再生研究（英文版）

基　　金：supported by the Start-up Fund for new faculty from the Hong Kong Polytechnic University(PolyU)(A0043215)(to SA);the General Research Fund and Research Impact Fund from the Hong Kong Research Grants Council(15106018,R5032-18)(to DYT);the Research Center for SHARP Vision in PolyU(P0045843)(to SA);the InnoHK scheme from the Hong Kong Special Administrative Region Government(to DYT).

摘　　要：Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The r

关 键 词：age-related macular degeneration anti-aging interventions autophagy calorie restriction diabetic retinopathy exercise glaucoma NEUROMODULATION PHAGOCYTOSIS photoreceptor outer segment degradation retinal aging transcription factor EB 

分 类 号：R774.1[医药卫生—眼科]