中山大学学报（医学科学版）2025，Vol.46Issue(6)：945-954,10.
正常眼压青光眼相关基因的研究进展
Research Progress on Genes Related to Normal Tension Glaucoma
摘要
Abstract
Normal tension glaucoma(NTG)is recognized as a distinct subtype of primary open-angle glaucoma,characterized by normal intraocular pressure(IOP<21 mmHg)in conjunction with progressive optic neuropathy,retinal ganglion cell(RGC)apoptosis,and visual field defects.The pathogenesis of NTG is predominantly independent of IOP,with fundamental processes involving genetic and mitochondrial factors,including RGC degeneration,neuroinflammation,mitochondrial dysfunction,and genetic predisposition.This article systematically reviews the IOP-independent and gene-driven mechanisms underlying NTG,with a particular focus on the roles of OPTN,TBK1,FOXC1,and OPA1 in inducing RGC damage through pathways such as mitochondrial dysfunction,glial cell activation,inflammatory signaling,apoptosis,and axonal degeneration.Among these genes,OPTN and TBK1 collectively contribute to the development of NTG by disrupting autophagy-mitochondrial homeostasis,causing defects in axonal transport,and activating neuroinflammatory pathways.FOXC1 is implicated in the progression of RGC degeneration through transcriptional regulation,while mutations in OPA1 lead to mitochondria-dependent RGC apoptosis.Additionally,this article provides a comprehensive review of the epigenetic regulation of METTL23,mitochondrial DNA mutations,the role of Alcadein α in axonal transport,the correlation between genes associated with primary open-angle glaucoma(POAG)and normal-tension glaucoma(NTG),as well as susceptibility loci identified through genome-wide association studies(GWAS).In the realm of translational research,recent advancements in therapeutic studies encompass strategies such as targeting OPTN E50K,inhibiting CRMP2 phosphorylation,and employing gene augmentation,gene silencing,and gene editing techniques.The etiology of NTG is complex,predominantly independent of intraocular pressure(IOP),and arises from the interplay between genetic and environmental factors.This article seeks to promote mechanism-based technological innovation,optimize neuroprotective strategies for NTG,and enhance clinical translation,ultimately aiming to achieve precise treatment and improve visual function outcomes for patients.关键词
正常眼压性青光眼/视网膜神经节细胞/神经保护治疗/视神经蛋白基因/TANK结合激酶1基因Key words
normal tension glaucoma/retinal ganglion cell/neuroprotective therapy/OPTN/TBK1分类
医药卫生引用本文复制引用
胡昊,梁亮..正常眼压青光眼相关基因的研究进展[J].中山大学学报（医学科学版）,2025,46(6):945-954,10.基金项目
国家自然科学基金(81770920) （81770920）
眼科学国家重点实验室开放课题(303060202400383) （303060202400383）
