{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:52:36Z","timestamp":1777909956523,"version":"3.51.4"},"reference-count":61,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Metabolic stress and associated mitochondrial dysfunction are implicated in retinal degeneration irrespective of the underlying cause. We identified seven unique chemicals from a Chembridge DiverSET screen and tested their protection against photoreceptor cell death in cell- and animal-based approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Calcium overload (A23187) was triggered in 661W murine photoreceptor-derived cells, and changes in redox potential and real-time changes in cellular metabolism were assessed using the MTT and Seahorse Biosciences XF assay, respectively. Cheminformatics to compare structures, and biodistribution in the living pig eye aided in selection of the lead compound.\n                      <jats:italic toggle=\"yes\">In-situ<\/jats:italic>\n                      , retinal organ cultures of rd1 mouse and S334ter-line-3 rat were tested,\n                      <jats:italic toggle=\"yes\">in-vivo<\/jats:italic>\n                      the light-induced retinal degeneration in albino Balb\/c mice was used, assessing photoreceptor cell numbers histologically.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Of the seven chemicals, six were protective against A23187- and IBMX-induced loss of mitochondrial capacity, as measured by viability and respirometry in 661W cells. Cheminformatic analyses identified a unique pharmacophore with 6 physico-chemical features based on two compounds (CB11 and CB12). The protective efficacy of CB11 was further shown by reducing photoreceptor cell loss in retinal explants from two retinitis pigmentosa rodent models. Using eye drops, CB11 targeting to the pig retina was confirmed. The same eye drops decreased photoreceptor cell loss in light-stressed Balb\/c mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      New chemicals were identified that protect from mitochondrial damage and lead to improved mitochondrial function. Using\n                      <jats:italic toggle=\"yes\">ex-vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in-vivo<\/jats:italic>\n                      models, CB11 decreased the loss of photoreceptor cells in murine models of retinal degeneration and may be effective as treatment for different retinal dystrophies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2020.0140","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T16:17:41Z","timestamp":1620145061000},"page":"367-378","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Newly Identified Chemicals Preserve Mitochondrial Capacity and Decelerate Loss of Photoreceptor Cells in Murine Retinal Degeneration Models"],"prefix":"10.1177","volume":"37","author":[{"given":"Craig","family":"Beeson","sequence":"first","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri K.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Perron","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mausumi","family":"Bandyopadhyay","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecile","family":"Nasarre","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyda","family":"Beeson","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard F.","family":"Comer","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher C.","family":"Lindsey","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick G.","family":"Schnellmann","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USA."},{"name":"Research Service, Southern Arizona VA Healthcare System, Tucson, Arizona, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e4rbel","family":"Rohrer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, USA."},{"name":"Research Service, Ralph H Johnson VA Medical Center, Charleston, South Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12203"},{"key":"e_1_3_5_3_2","first-page":"263","article-title":"From mice to men: the cyclic GMP phosphodiesterase gene in vision and disease","volume":"36","author":"Farber D.B.","year":"1995","unstructured":"Farber D.B. 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