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However, despite several lines of investigation, the complete mechanism of the response has evaded a comprehensive description. The standard model implicates the rod photoreceptors and a signaling molecule termed the \u2018light-rise substance\u2019 that binds to an apical membrane \u2018light-rise receptor\u2019 or is transported across the membrane to elevate intracellular calcium concentration. The identity of the calcium activated chloride channel in the basolateral membrane was thought to be bestrophin, given the association of mutations in the hbest1 gene with Best Vitelliform Macular Dystrophy. However, recent findings have implicated a member of the anoctamin family as the calcium activated chloride channel with bestrophin regulating intracellular calcium in conjunction with the L-type calcium channel. How the changes in intracellular calcium are manifested as well as how the interaction with light in the dark-adapted state gives rise to the slow-dark and -light damped oscillations are yet to be described fully. This review summarizes the cellular mechanisms of the RPE that have been implicated in the generation of the light-rise and describes the likely candidates for the light-rise substance. A companion paper provides a summary of the bestrophinopathies and possible clinical modifications to enhance the EOG\u2019s clinical utility.<\/jats:p>","DOI":"10.1007\/s10633-026-10103-z","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T18:34:08Z","timestamp":1776278048000},"page":"267-285","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Review of the clinical electrooculogram - Part 1: Mechanism of the Light-Rise"],"prefix":"10.1007","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3994-1700","authenticated-orcid":false,"given":"Paul A.","family":"Constable","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1357-9395","authenticated-orcid":false,"given":"Lynne","family":"Loh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6321-6931","authenticated-orcid":false,"given":"Maja \u0160u\u0161tar","family":"Habjan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6453-5851","authenticated-orcid":false,"given":"Srikanta Kumar","family":"Padhy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"10103_CR1","first-page":"3033","volume":"32","author":"JL Edelman","year":"1991","unstructured":"Edelman JL, Miller SS (1991) Epinephrine stimulates fluid absorption across bovine retinal pigment epithelium. 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