Long-Acting RXR Agonism Preserves Retinal Function and Modulates Inflammation in Diabetic Retinopathy
Year: 2026
Type: other
Abstract: 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, PPAR, and LXRβ and their lipid metabolism targets (Abca1, Scd1, 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 retina. A single intravitreal injection of UAB126-MP provided extended drug exposure for up to six months and increased retinal RXRα expression. Functionally, UAB126-MP preserved scotopic and photopic electroretinographic responses at two months and sustained cone photoreceptor function at six months. However, it did not reduce acellular capillaries. At six 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–mediated pathways, underscoring its potential as a long-acting therapeutic strategy for DR.
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7168952103