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Numerous investigations have indicated that the onset and progression of these conditions are significantly linked to oxidative stress (OS) affecting the eye. The Keap1\u2010Nrf2\u2010ARE signaling pathway is a well\u2010established mechanism that defends the body against OS and inflammation. This pathway is also implicated in the advancement of AREDs. However, the contribution of Nrf2 is likely to be disease\u2010context dependent, and in multifactorial conditions such as glaucoma and dry eye disease, OS should be viewed as one interacting mechanism among several pathogenic processes rather than the sole or dominant driver. Nuclear factor (erythroid\u2010derived 2)\u2010like 2 (Nrf2) serves as a key modulator of numerous life processes, playing a critical role in antioxidant mechanisms, anti\u2010inflammatory activities, antifibrotic responses, and cancer development. This review emphasizes the possible role of Nrf2 in the onset and progression of AREDs. Additionally, it explores various Nrf2 activators, encompassing noncoding RNAs and external substances, that regulate Nrf2 expression via distinct pathways within ocular disease models and eye cells, thereby safeguarding them from harmful alterations. However, most evidence supporting Nrf2\u2010targeted interventions in age\u2010related eye diseases remains preclinical, and important issues including disease\u2010specific ocular delivery, target engagement in human tissues, long\u2010term safety, and the potential risks of chronic Nrf2 activation must be addressed before clinical translation can be considered feasible. Consequently, Nrf2 may represent a significant target for the safeguarding of ocular cells against assorted stressors and the prevention of ocular ailments.<\/jats:p>","DOI":"10.1002\/jbt.70968","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:33:53Z","timestamp":1785144833000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting of Nuclear Factor Erythroid 2\u2010Related Factor 2 (NRF2) Signaling Pathway in Age\u2010Related Eye Diseases: Molecular Mechanisms and Opportunities for therapy"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3994-6197","authenticated-orcid":false,"given":"Fu","family":"XinYu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Chengdu Medical College SiChuan ChengDu 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