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DRN is characterized by apoptosis of retinal ganglion cells (involves alterations in retinal ganglion cells [RGCs], photoreceptors, amacrine cells and bipolar cells and so on), reactive gliosis, and reduced retinal neuronal function. Tau, a microtubule\u2010associated protein, is a key mediator of neurotoxicity in neurodegenerative diseases, with functions in phosphorylation\u2010dependent microtubule assembly and stabilization, axonal transport, and neurite outgrowth. The hyperphosphorylated tau (p\u2010tau) loses its ability to bind to microtubules and aggregates to form paired helical filaments (PHFs), which further form neurofibrillary tangles (NFTs), leading to abnormal cell scaffolding and cell death. Studies have shown that p\u2010tau can cause degeneration of RGCs in DR, making tau pathology a new pathophysiological model for DR. Here, we review the mechanisms by which p\u2010tau contribute to DRN, including insulin resistance or lack of insulin, mitochondrial damage such as mitophagy impairment, mitochondrial axonal transport defects, mitochondrial bioenergetics dysfunction, and impaired mitochondrial dynamics, Abeta toxicity, and inflammation. Therefore, this article proposes that tau protein hyperphosphorylation plays a crucial role in the pathogenesis of DRN and may serve as a novel therapeutic target for combating DRN.<\/jats:p>","DOI":"10.1155\/joph\/3278794","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T01:10:51Z","timestamp":1741828251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Role of Tau Protein Hyperphosphorylation in Diabetic Retinal 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