{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T19:27:45Z","timestamp":1787254065887,"version":"build-2736575974"},"reference-count":39,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY035539"],"award-info":[{"award-number":["R01EY035539"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Diabetic retinopathy (DR) is a leading cause of vision loss and is associated with reduced nuclear retinoid X receptor (RXR) activity. Retinal explants exposed to high glucose showed downregulation of RXR, peroxisome proliferator\u2013activated receptor (PPAR), and liver X receptor-\u03b2 and their lipid metabolism targets (Abca1, Scd1, and Acox1). Supplementation with the RXR agonist UAB126 restored nuclear receptor signaling and preferentially activated RXR\/PPAR heterodimers. We evaluated UAB126 microparticles (UAB126-MP), a sustained-release RXR agonist formulation, for pharmacokinetic, molecular, and functional effects in db\/db mouse retinas. A single intravitreal injection of UAB126-MP provided extended drug exposure for up to 6 months and increased retinal RXR\u03b1 expression. Functionally, UAB126-MP preserved scotopic and photopic electroretinographic responses at 2 months and sustained cone photoreceptor function at 6 months. However, it did not reduce acellular capillaries. At 6 months, immunostaining and flow cytometry revealed decreased retinal macrophage\/microglial infiltration and reduced CD45-positive myeloid cells and monocytes. These findings indicate that RXR agonism supports neuronal protection and immune modulation but does not prevent vasodegeneration, suggesting primarily neuroprotective and anti-inflammatory actions. Collectively, UAB126-MP confers durable retinal protection through nuclear receptor\u2013mediated pathways, underscoring its potential as a long-acting therapeutic strategy for DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>High glucose exposure of retinal explants reduces expression of nuclear receptors retinoid X receptor (RXR), peroxisome proliferator\u2013activated receptor, and liver X receptor-\u03b2, and treatment with UAB126 increases the formation of RXR-peroxisome proliferator\u2013activated receptor heterodimers. Sustained release of UAB126-loaded microparticles enables intravitreal drug delivery for up to 6 months. Intravitreal UAB126 microparticles injection in diabetic mice confers long-term neuroprotection and anti-inflammatory benefits. RXR-targeted therapy represents a promising approach strategy for managing diabetic retinopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db26-0053","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:33:47Z","timestamp":1784223227000},"page":"1554-1567","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Long-Acting RXR Agonism Preserves Retinal Function and Modulates Inflammation in Diabetic Retinopathy"],"prefix":"10.2337","volume":"75","author":[{"given":"Emory","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, The University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Kaffash","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Virginia Commonwealth University School of Pharmacy 2 , Richmond, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadeela","family":"Sheini","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, The University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Rennhack","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, The University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheli Severo","family":"Sielski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, The University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assylbek","family":"Zhylkibayev","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Wake Forest University School of Medicine 3 , Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Li","family":"Calzi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, The University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagun","family":"Poudel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Virginia Commonwealth University School of Pharmacy 2 , Richmond, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatram","family":"Atigadda","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Alabama at Birmingham 4 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingguo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Virginia Commonwealth University School of Pharmacy 2 , Richmond, VA"},{"name":"Department of Ophthalmology, Virginia Commonwealth University School of Medicine 5 , Richmond, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6470-0255","authenticated-orcid":false,"given":"Maria B.","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, The University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9060-856X","authenticated-orcid":false,"given":"Marina S.","family":"Gorbatyuk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Wake Forest University School of Medicine 3 , Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"2026082014521098500_B1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4103\/ijem.ijem_480_21","article-title":"Diabetic retinopathy: an overview 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