{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:04:41Z","timestamp":1785420281277,"version":"3.56.0"},"reference-count":142,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571232"],"award-info":[{"award-number":["82571232"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82571232"],"award-info":[{"award-number":["82571232"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20240122"],"award-info":[{"award-number":["BK20240122"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Retinal neurovascular unit (RNVU) dysfunction underlies major blinding and neurodegenerative conditions including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal ischemia\u2013reperfusion (RIR) injury, and Alzheimer\u2019s disease (AD)-associated retinopathy. Within the RNVU, calcium ions coordinate neurotransmission, glial activation, vascular tone, and blood\u2013retinal barrier maintenance, and calcium dysregulation is emerging as a unifying pathogenic hub across these conditions. Although upstream triggers differ, including mechanical stress in glaucoma, hyperglycemia in DR, oxidative damage in AMD, ischemic energy failure in RIR, and amyloid-\u03b2\u2013driven endoplasmic reticulum stress in AD, all converge on disruption of intracellular calcium homeostasis, producing shared downstream consequences including excitotoxic injury of retinal ganglion cells (RGCs), M\u00fcller cell reactive gliosis, and pericyte hypercontraction. Broad-spectrum calcium channel blockade has shown limited clinical success, underscoring the need for cell-type-specific and pathway-selective approaches. This review therefore catalogs key interventional nodes, including transient receptor potential (TRP) channel antagonists, T-type calcium channel inhibitors, calcium\/calmodulin-dependent protein kinase II (CaMKII) suppressors, and mitochondrial permeability transition pore (mPTP) inhibitors, and discusses how precision targeting of these pathways may restore RNVU homeostasis and open a therapeutic window into central nervous system (CNS) degenerative disorders.<\/jats:p>","DOI":"10.3390\/biom16060763","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Calcium at the Helm: Mechanisms and Therapeutic Targets in the Retinal Neurovascular Unit"],"prefix":"10.3390","volume":"16","author":[{"given":"Siyuan","family":"Ding","sequence":"first","affiliation":[{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Ophthalmology, The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Li","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Ophthalmology, The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4201-7208","authenticated-orcid":false,"given":"Ziyi","family":"Chen","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Ophthalmology, The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Bai","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Ophthalmology, The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keran","family":"Li","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Ophthalmology, The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1001\/archopht.121.4.547","article-title":"Retinal oxygen: Fundamental and clinical aspects","volume":"121","author":"Linsenmeier","year":"2003","journal-title":"Arch. 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