{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:03:26Z","timestamp":1785438206083,"version":"3.56.0"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>High myopia is characterized not only by a progressive increase in refractive error but also, more critically, by its significant association with retinal degenerative diseases, posing a considerable public health concern. An increasing amount of research illustrates the role of several epigenetic regulatory mechanisms\u2014including DNA methylation, modifications of histones, non-coding RNAs, and additional epigenetic elements\u2014in the onset and advancement of high myopia. This condition primarily results from the pathological elongation of the eye axis, which alters the mechanical stress on the fundus and accelerates degenerative changes in the retina. The degenerative alterations include modifications in the structure and morphology of retinal pigment epithelial (RPE) cells, along with the restructuring of the outer layers of the retina. Notably, the mechanical stimuli induced by these biomechanical changes can create a form of cellular memory that continues to influence RPE cell behavior even after the initial force is removed. Cells may sense mechanical signals directly through cytoskeleton-associated membrane receptors or indirectly via intracellular biochemical cascades that modulate gene expression in response to environmental cues. This review proposes a conceptual framework to examine the central role of epigenetic modifications in retinal degeneration associated with high myopia. It highlights that RPE cells function as key responders to mechanical stress, capable of forming cellular memory and adaptive responses that drive outer retinal remodeling and exacerbate degenerative processes. This research aims to enhance the comprehension of the pathogenesis related to retinal degenerative alterations linked to high myopia by clarifying the processes involved in mechanical signal transduction and the epigenetic regulation of cellular functions.<\/jats:p>","DOI":"10.3389\/fmed.2026.1780606","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:32:37Z","timestamp":1774935157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Associations between mechanical stress and epigenetic modifications in outer retinal layer remodeling in high myopia"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiayu","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shenzhen Traditional Chinese Medicine Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine","place":["Harbin, China"]},{"name":"Department of Ophthalmology, First Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shenzhen Traditional Chinese Medicine Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1111\/aos.70021","article-title":"Myopia 2025: epidemiology, pathophysiology, treatment and complications","volume":"103","author":"P\u00e4rssinen","year":"2025","journal-title":"Acta 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