老年视力障碍药物靶点的研究进展

doi:10.3969/j.issn.1003-9198.2026.03.004

摘要/Abstract

摘要： 老年视力障碍的全球疾病负担沉重,涵盖年龄相关性白内障、年龄相关性黄斑变性、青光眼、糖尿病视网膜病变、干眼症、屈光不正、视网膜静脉阻塞等多种类型。当前临床治疗方案存在逐渐耐药、逆转损伤困难、药物依从性差、治疗选项有限等局限性,不断进行的药物靶点研究成为突破治疗瓶颈的关键。本文系统梳理了上述常见老年视力障碍的核心病理机制,综述了近年相关药物靶点的研究进展,最后,本文提出未来需聚焦多靶点协同治疗策略,同时发展新型递药技术,结合基因编辑技术,开发老年视力障碍新疗法。

关键词: 视力障碍, 老年人, 药物靶点, 年龄相关性白内障, 视网膜病变

Abstract: The global disease burden of visual impairment in the elderly is substantial, encompassing various types such as age-related cataract, age-related macular degeneration, glaucoma, diabetic retinopathy, xerophthalmia, refractive errors, and retinal vein occlusion. Current clinical treatment options face limitations including gradual drug resistance, difficulty in reversing damage, poor medication adherence, and limited therapeutic choices. Ongoing research into drug targets has become key to breaking through these therapeutic bottlenecks. This article systematically reviews the core pathological mechanisms of the aforementioned common visual impairments, summarizes recent advances in related drug target research, and finally proposes that future efforts should focus on multi-target synergistic treatment strategies, develop novel drug delivery technologies, and combine gene editing techniques to develop new therapies for visual impairment in the elderly.

Key words: visual impairment, aged, drug targets, age-related cataract, retinopathy

中图分类号:

R 77

李铭麟, 李敏锋, 曾三龙, 梁庆静, 刘继业, 骆建文. 老年视力障碍药物靶点的研究进展[J]. 实用老年医学, 2026, 40(3): 234-240.

LI Minglin, LI Minfeng, ZENG Sanlong, LIANG Qingjing, LIU Jiye, LUO Jianwen. Research advances in drug targets for visual impairment in the elderly[J]. Practical Geriatrics, 2026, 40(3): 234-240.

参考文献

[1] XU S, CHEN J, WANG X, et al. Trends and projections of the burden of visual impairment in Asia: findings from the Global Burden of Disease Study 2021[J]. Asia Pac J Ophthalmol: Phila, 2025, 14(3): 100196.
[2] EKICI E, MOGHIMI S. Advances in understanding glaucoma pathogenesis: a multifaceted molecular approach for clinician scientists[J]. Mol Aspects Med, 2023, 94: 101223.
[3] LI C, LU Y, SONG Z, et al. A real-world data analysis of ocular adverse events linked to anti-VEGF drugs: a WHO-VigiAccess study[J]. Front Pharmacol, 2024, 15: 1398783.
[4] MULLIGAN K, SEABURY S A, DUGEL P U, et al. Economic value of anti-vascular endothelial growth factor treatment for patients with wet age-related macular degeneration in the United States[J]. JAMA Ophthalmol, 2020, 138(1): 40-47.
[5] YEE H, WONG C M J, GUPTA P, et al. Prevalence, risk determinants, and burden of undiagnosed age-related eye diseases among older Asian adults[J]. JAMA Ophthalmol, 2025: e254623.
[6] 卫佳奇, 张琇雯, 黄滔敏. 白内障的药物治疗及研究进展[J]. 眼科学报, 2025, 40(7): 565-573.
[7] ZHANG X, LIU B, LAL K, et al. Antioxidant system and endoplasmic reticulum stress in cataracts[J]. Cell Mol Neurobiol, 2023, 43(8): 4041-4058.
[8] SUN Y, HONG Y, NING L, et al. FOXO3 protects lens epithelial cells from UVB-induced oxidative stressvia the AMPK/FOXO3 signaling pathway[J]. FASEB J, 2025, 39(17): e71039.
[9] YANG W, ZHENG Y, CHEN S, et al. Aging of the human eye lens: epigenetic landscape and therapeutic targets in age-related cataracts (Review)[J]. Int J Mol Med, 2025, 56(6): 216.
[10] JOSEF J D, KAUR R P, BHATTACHARYA S K, et al. Lipids as pharmacological targets in age-related lens disease[J]. Trends Pharmacol Sci, 2025. DOI: 10.1016/j.tips.2025.11.008.
[11] LI J, SUN Q, QIU X, et al. Downregulation of AMPK dependent FOXO3 and TFEB involves in the inhibition of autophagy in diabetic cataract[J]. Curr Eye Res, 2022, 47(4): 555-564.
[12] KHAN M, VERMA L. Crosstalk between signaling pathways (Rho/ROCK, TGF-β and Wnt/β-Catenin Pathways/PI3K-AKT-mTOR) in cataract: a mechanistic exploration and therapeutic strategy[J]. Gene, 2025, 947: 149338.
[13] ZHANG L L, YU J M, FAN Z X, et al. Regulated cell death in age-related macular degeneration: regulatory mechanisms and therapeutic potential[J]. J Pharm Anal, 2025, 15(11): 101285.
[14] WAGH V, DAMODAREN N, MITTAL S K, et al. Cellular senescence: an emerging player in the pathogenesis of AMD[J]. Adv Exp Med Biol, 2025, 1468: 33-37.
[15] SIVAPRASAD S, WONG T Y, GARDNER T W, et al. Diabetic retinal disease [J]. Nat Rev Dis Primers, 2025, 11(1): 62.
[16] ROMANO F, LAMANNA F, GABRIELLE P H, et al. Update on retinal vein occlusion[J]. Asia Pac J Ophthalmol: Phila, 2023, 12(2): 196-210.
[17] 于丽灵. 多病因眼底病变的发病机制与治疗进展[J]. 河北北方学院学报(自然科学版), 2026, 42(2): 57-62.
[18] LI X, WANG J, WANG L, et al. Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging[J]. Signal Transduct Target Ther, 2022, 7(1): 162.
[19] GAO F, TOM E, RYDZ C, et al. Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice[J]. Sci Transl Med, 2025, 17(817): eads5769.
[20] JI R, ISHIKAWA K, TAN W, et al. Liposome encapsulation enhances ripasudil therapeutic efficacy against proliferative vitreoretinal diseases: implications in advanced ocular treatment[J]. Invest Ophthalmol Vis Sci, 2025, 66(6): 56.
[21] ZHANG Y, PAN T, YANG Y, et al. Oridonin attenuates diabetic retinopathy progression by suppressing NLRP3 inflammasome pathway[J]. Mol Cell Endocrinol, 2025, 596: 112419.
[22] REN K, LI X. MCC950 targets the ROS-NEK7-NLRP3 axis to improve type 2 diabetic retinopathy[J]. Sci Rep, 2025, 15(1): 32637.
[23] LU Y, YU X, CHEN Y, et al. Safety and efficacy of multiple escalating doses of RC28-E for neovascular age-related macular degeneration: a phase 1b trial[J]. Ophthalmol Ther, 2024, 13(9): 2405-2415.
[24] KHANANI A M, BAKRI S J, REGILLO C, et al. Novel targets beyond vascular endothelial growth factor - A inhibition: improving vision with neovascular age-related macular degeneration treatment[J]. Eye: Lond, 2025, 39(17): 3045-3057.
[25] CHENG Y, ZHANG M, LI C, et al. Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling[J]. Nat Commun, 2025, 16(1): 1332.
[26] CHEN K Y, CHAN H C, CHAN C M. Effectiveness and safety of anti-vascular endothelial growth factor therapies for macular edema in retinal vein occlusion: a systematic review and network meta-analysis of randomized controlled trials[J]. Surv Ophthalmol, 2025, 70(6): 1067-1089.
[27] QIAN H Y, WEI X H, HUANG J O. Inflammatory mechanisms in diabetic retinopathy: pathogenic roles and therapeutic perspectives[J]. Am J Transl Res, 2025, 17(8): 6262-6274.
[28] XU C, LI H, XU Q, et al. Dapagliflozin ameliorated retinal vascular permeability in diabetic retinopathy rats by suppressing inflammatory factors[J]. J Diabetes Complications, 2024, 38(3): 108631.
[29] YANG X, ZHANG Y, ZHOU Y, et al. CaMK2A/CREB pathway activation is associated with enhanced mitophagy and neuronal apoptosis in diabetic retinopathy[J]. Sci Rep, 2025, 15(1): 12516.
[30] LIU D, LIU Z, LIAO H, et al. Ferroptosis as a potential therapeutic target for age-related macular degeneration[J]. Drug Discov Today, 2024, 29(4): 103920.
[31] WANG X, SUN L, HAN X, et al. The molecular mechanisms underlying retinal ganglion cell apoptosis and optic nerve regeneration in glaucoma (Review)[J]. Int J Mol Med, 2025, 55(4): 63.
[32] LIU Y, WANG A, CHEN C, et al. Microglial cGAS-STING signaling underlies glaucoma pathogenesis[J]. Proc Natl Acad Sci U S A, 2024, 121(36): e2409493121.
[33] YE M, HU Y, ZHAO B, et al. TBK1 knockdown alleviates axonal transport deficits in retinal ganglion cellsvia mTORC1 activation in a retinal damage mouse model[J]. Invest Ophthalmol Vis Sci, 2023, 64(10): 1.
[34] GUPTA V, CHITRANSHI N, GUPTA V, et al. TrkB receptor agonist 7, 8 dihydroxyflavone is protective against the inner retinal deficits induced by experimental glaucoma[J]. Neuroscience, 2022, 490: 36-48.
[35] BRITTEN-JONES A C, WANG M T M, SAMUELS I, et al. Epidemiology and risk factors of dry eye disease: considerations for clinical management[J]. Medicina: Kaunas, 2024, 60(9): 1458.
[36] DIKMETAS O, KAPUCU Y, COŞAN S, et al. Systemic secukinumab treatment in patients with ankylosing spondylitis: the relationship between systemic and tear proinflammatory cytokines and ocular surface findings: a pilot study[J]. Clin Rheumatol, 2025, 44(7): 2775-2782.
[37] ZHANG D, CHEN T, LIANG Q, et al. A first-in-human, prospective pilot trial of umbilical cord-derived mesenchymal stem cell eye drops therapy for patients with refractory non-Sjögren’s and Sjögren’s syndrome dry eye disease[J]. Stem Cell Res Ther, 2025, 16(1): 202.
[38] GE H, DI G, LI B, et al. Reticulated retinoic acid synthesis is implicated in the pathogenesis of dry eye in Aqp5 deficiency mice[J]. Invest Ophthalmol Vis Sci, 2024, 65(8): 25.
[39] DIAZ D, SASSANI J P, ZAGON I S, et al. Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats[J]. Exp Biol Med: Maywood, 2024, 249: 10175.
[40] GBD 2019 Blindness and Vision Impairment Collaborators. Vision Loss Expert Group of the Global Burden of Disease Study. Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study[J]. Lancet Glob Health, 2021, 9(2): e130-e143.
[41] KUMARI S S, VARADARAJ K. Aquaporin 0 plays a pivotal role in refractive index gradient development in mammalian eye lens to prevent spherical aberration[J]. Biochem Biophys Res Commun, 2014, 452(4): 986-991.
[42] KU H, CHEN J J, CHEN W, et al. The role of transforming growth factor beta in myopia development[J]. Mol Immunol, 2024, 167: 34-42.
[43] ZENG B, ZHANG C, LIANG Y, et al. Single-cell RNA sequencing highlights a significant retinal Müller glial population in dry age-related macular degeneration[J]. iScience, 2025, 28(5): 112464.
[44] YU J, YIN Y, LENG Y, et al. Emerging strategies of engineering retinal organoids and organoid-on-a-chip in modeling intraocular drug delivery: current progress and future perspectives[J]. Adv Drug Deliv Rev, 2023, 197: 114842.
[45] FADAHUNSI A A, UZOETO H O, OKORO N O, et al. Revolutionizing drug discovery: an AI-powered transformation of molecular docking[J]. Med Chem Res, 2024, 33(12): 2187-2203.