{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:44:34Z","timestamp":1785300274098,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIHR"},{"name":"The Krembil Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Degenerative retinal diseases associated with photoreceptor loss are a leading cause of visual impairment worldwide, with limited treatment options. Phenotypic profiling coupled with medicinal chemistry were used to develop a small molecule with proliferative effects on retinal stem\/progenitor cells, as assessed in vitro in a neurosphere assay and in vivo by measuring Msx1-positive ciliary body cell proliferation. The compound was identified as having kinase inhibitory activity and was subjected to cellular pathway analysis in non-retinal human primary cell systems. When tested in a disease-relevant murine model of adult retinal degeneration (MNU-induced retinal degeneration), we observed that four repeat intravitreal injections of the compound improved the thickness of the outer nuclear layer along with the regeneration of the visual function, as measured with ERG, visual acuity, and contrast sensitivity tests. This serves as a proof of concept for the use of a small molecule to promote endogenous regeneration in the eye.<\/jats:p>","DOI":"10.3390\/ijms25031521","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T04:05:46Z","timestamp":1706241946000},"page":"1521","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Small-Molecule-Directed Endogenous Regeneration of Visual Function in a Mammalian Retinal Degeneration Model"],"prefix":"10.3390","volume":"25","author":[{"given":"Daphna","family":"Mokady","sequence":"first","affiliation":[{"name":"Endogena Therapeutics, Inc., 661 University Ave, Toronto, ON M5G 0B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Charish","sequence":"additional","affiliation":[{"name":"Endogena Therapeutics, Inc., 661 University Ave, Toronto, ON M5G 0B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Barretto-Burns","sequence":"additional","affiliation":[{"name":"Endogena Therapeutics, Inc., 661 University Ave, Toronto, ON M5G 0B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth N.","family":"Gris\u00e9","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Donnelly Centre Rm 1110, 160 College Street, Toronto, ON M5S 3E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1679-4605","authenticated-orcid":false,"given":"Brenda L. 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