{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:27:04Z","timestamp":1783578424177,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NEI","award":["EY022678"],"award-info":[{"award-number":["EY022678"]}]},{"name":"NEI","award":["EY029809"],"award-info":[{"award-number":["EY029809"]}]},{"name":"NEI","award":["P30EY016665"],"award-info":[{"award-number":["P30EY016665"]}]},{"name":"the RRF-Rebecca Meyer Brown Professorship of McPherson Eye Research Institute","award":["EY022678"],"award-info":[{"award-number":["EY022678"]}]},{"name":"the RRF-Rebecca Meyer Brown Professorship of McPherson Eye Research Institute","award":["EY029809"],"award-info":[{"award-number":["EY029809"]}]},{"name":"the RRF-Rebecca Meyer Brown Professorship of McPherson Eye Research Institute","award":["P30EY016665"],"award-info":[{"award-number":["P30EY016665"]}]},{"name":"University of Wisconsin-Madison Vision Core","award":["EY022678"],"award-info":[{"award-number":["EY022678"]}]},{"name":"University of Wisconsin-Madison Vision Core","award":["EY029809"],"award-info":[{"award-number":["EY029809"]}]},{"name":"University of Wisconsin-Madison Vision Core","award":["P30EY016665"],"award-info":[{"award-number":["P30EY016665"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The structurally and genetically distinct sigma-1 receptor (S1R) and sigma-2 receptor (S2R) comprise a unique class of drug binding sites. Their alleles are associated with human diseases involving neuronal systems, such as age-related macular degeneration (AMD) characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. Previous studies have suggested neuroprotective benefits for the brain and retina from pharmacological modulation of S1R and\/or S2R. However, the effect of such modulation on AMD pathology remains underexplored. Here, we evaluated S1R- or S2R-selective modulation in an AMD-related model of Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice with a disrupted visual cycle that predisposes RPE and photoreceptors to illumination-induced damage. For S1R modulation, we used (+)-pentazocine, which is a high-affinity S1R-selective drug. For S2R modulation, we chose CM398, a high-affinity and highly S2R-selective ligand with drug-like properties. Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice received a single i.p. injection of (+)-pentazocine or CM398 or vehicle 30 min before illumination. Pretreatment with (+)-pentazocine improved electroretinogram a- and b-waves compared to that with vehicle. Consistently, in another AMD-related mouse model induced by tail-vein injected NaIO3, S1R genetic ablation aggravated photoreceptor loss. In Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice, pretreatment with CM398 appeared to partially avert illumination-induced photoreceptor loss and autofluorescent granule formation that signals RPE damage, as revealed by optical coherence tomography. Thus, this study using AMD-related models provides evidence of photoreceptor protection afforded by selective modulation of S1R or S2R.<\/jats:p>","DOI":"10.3390\/genes13122386","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T06:58:29Z","timestamp":1671433109000},"page":"2386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Retinal Photoreceptor Protection in an AMD-Related Mouse Model by Selective Sigma-1 or Sigma-2 Receptor Modulation"],"prefix":"10.3390","volume":"13","author":[{"given":"Timur A.","family":"Mavlyutov","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-4442","authenticated-orcid":false,"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-2915","authenticated-orcid":false,"given":"Christopher R.","family":"McCurdy","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-358X","authenticated-orcid":false,"given":"Bikash","family":"Pattnaik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin, Madison, WI 53705, USA"},{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6947-1578","authenticated-orcid":false,"given":"Lian-Wang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Wisconsin, Madison, WI 53705, USA"},{"name":"Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin, Madison, WI 53705, USA"},{"name":"Department of Ophthalmology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","first-page":"517","article-title":"The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog","volume":"197","author":"Martin","year":"1976","journal-title":"J. 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