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Meta\u202fII initiates the phototransduction cascade, culminating in membrane hyperpolarization. To investigate how meta\u202fII lifetime shapes the rod photoresponse, we studied a knock-in mouse expressing\n                    <jats:italic>E122Q<\/jats:italic>\n                    rhodopsin, a mutant pigment with a shortened meta\u202fII lifetime. Microspectrophotometry confirmed that\n                    <jats:italic>E122Q<\/jats:italic>\n                    rhodopsin is blue-shifted in its absorbance spectrum and exhibits significantly faster meta\u202fII decay than wild-type (WT). Patch-clamp recordings revealed that this shortened lifetime had little effect on response kinetics or on the dominant time constant of recovery after bright flashes. However, following pigment bleaching, rods expressing\n                    <jats:italic>E122Q<\/jats:italic>\n                    showed markedly greater desensitization than WT, indicating that free\n                    <jats:italic>E122Q<\/jats:italic>\n                    opsin activates the phototransduction cascade more efficiently in darkness. To our knowledge, this is the first report of a rhodopsin mutation that alters free opsin-driven activation of phototransduction. Given that many disease-causing mutations affect dark adaptation, such opsin-based mechanisms may be more common than previously appreciated.\n                  <\/jats:p>","DOI":"10.1007\/s00359-026-01822-4","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:13:32Z","timestamp":1782450812000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["E122Q rhodopsin: pigment microspectrophotometry, photoreceptor light responses, and bleaching adaptation"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5248-5977","authenticated-orcid":false,"given":"Christopher J.","family":"Meredith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9978-0356","authenticated-orcid":false,"given":"Annabelle N.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-9577","authenticated-orcid":false,"given":"Alapakkam P.","family":"Sampath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9813-0342","authenticated-orcid":false,"given":"Gordon L.","family":"Fain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7999-8480","authenticated-orcid":false,"given":"Rikard","family":"Frederiksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"1822_CR1","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1111\/j.1471-4159.1981.tb04473.x","volume":"37","author":"A Ames III","year":"1981","unstructured":"Ames A III, Nesbett FB (1981) In vitro retina as an experimental model of the central nervous system. 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