{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:49:45Z","timestamp":1782478185035,"version":"3.54.5"},"reference-count":132,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Cell Communication and Signaling"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are hallmarks of many ophthalmic diseases; however, they have traditionally been examined as isolated pathological processes. Recent evidence indicates that these organelles are inextricably coupled through mitochondria\u2013endoplasmic reticulum contact sites, also known as mitochondria\u2010associated membranes (MAMs), which coordinate Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling, lipid transfer, mitochondrial dynamics, redox balance, and cell death decisions. Consequently, dysregulated ER\u2013mitochondria communication has emerged as a key vulnerability that links the cellular stress responses among diverse ocular tissues, including lens epithelial cells, retinal ganglion cells, the retinal pigment epithelium, and corneal endothelial cells. In this review, we summarize the recent advances involving the molecular architecture and regulatory function of ER\u2013mitochondria crosstalk. We focus on how the unfolded protein response signaling, pathological MAM remodeling, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dysregulation, and disrupted mitochondrial quality control collectively drive disease progression. By integrating evidence from cataract, glaucoma, diabetic retinopathy, age\u2010related macular degeneration, and Fuchs endothelial corneal dystrophy, we reveal that these disorders are not driven by a uniform mechanism of organelle failure, but rather by the dominance of pathological nodes along the ER\u2013mitochondria axis. We propose that ophthalmic diseases should be stratified based on these distinct failure nodes, which provides a mechanistic framework for developing therapeutics. Within this context, interventions targeting maladaptive ER stress, MAM destabilization, bioenergetic failure, or defective mitophagy should be considered complementary and context\u2010dependent strategies. By reframing ophthalmic disorders as diseases of inter\u2010organelle stress integration, this review positions the ER\u2013mitochondria axis as a modifiable upstream determinant of ocular cell fate, which provides a foundation for stage\u2010specific precision therapies.\n                  <\/jats:p>","DOI":"10.1002\/ccs3.70080","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T20:39:01Z","timestamp":1778963941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Crosstalk between endoplasmic reticulum stress and mitochondrial homeostasis: A new perspective on ophthalmic disease treatment"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4666-0663","authenticated-orcid":false,"given":"Luyang","family":"Jiang","sequence":"first","affiliation":[{"name":"Eyes Center Shangyu People's Hospital of Shaoxing Shaoxing University  Shaoxing Zhejiang 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9385-4851","authenticated-orcid":false,"given":"Jufen","family":"Liu","sequence":"additional","affiliation":[{"name":"Eyes Center Shangyu People's Hospital of Shaoxing Shaoxing University  Shaoxing Zhejiang China"},{"name":"School of Medicine Shaoxing University  Shaoxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2158-5894","authenticated-orcid":false,"given":"Yumin","family":"Tao","sequence":"additional","affiliation":[{"name":"The Affiliated Kangning Hospital of Ningbo University  Ningbo Zhejiang Province 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