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Updated: Jul 6, 2026
Retinal Pathophysiological Evaluation in a Rat Model
Published on: May 6, 2022
Retinoid X Receptor Activation Prevents Diabetic Retinopathy in Murine Models
Iuliia Dorofeeva1, Assylbek Zhylkibayev1, Irina V Saltykova1
1Department of Optometry and Vision Science, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Abstract:
Previously, the RXR agonist UAB126 demonstrated therapeutic potential to treat obese mice by controlling blood glucose levels (BGL) and altering the expression of genes associated with lipid metabolism and inflammatory response. The purpose of the study was to assess the effects of UAB126 on the progression of diabetic retinopathy (DR) in rodent models of type 1 diabetes (T1D), streptozotocin-induced, and type 2 diabetes (T2D), in db/db mice. UAB126 treatment was delivered either by oral gavage for 6 weeks or by topical application of eye drops for 2 weeks. At the end of the treatment, the retinal function of diabetic mice was assessed by electroretinography (ERG), and their retinal tissue was harvested for protein and gene expression analyses. Bone-marrow cells were isolated and differentiated into bone marrow-derived macrophages (BMDMs). The glycolysis stress test and the 2-DG glucose uptake analysis were performed. Our results demonstrated that in the UAB126-treated diabetic BMDMs, the ECAR rate and the 2-DG uptake were improved as compared to untreated diabetic BMDMs. In UAB126-treated diabetic mice, hyperglycemia was reduced and associated with the preservation of ERG amplitudes and enhanced AMPK activity. Retinas from diabetic mice treated with topical UAB126 demonstrated an increase in Rxr and Ppar and the expression of genes associated with lipid metabolism. Altogether, our data indicate that RXR activation is beneficial to preclinical models of DR.
Insights
The RXR agonist UAB126 improved glucose control and retinal function in diabetic mice. This suggests RXR activation may be a promising therapeutic strategy for diabetic retinopathy (DR).
Area of Science:
- Ophthalmology
- Endocrinology
- Metabolic Research
Background:
- Obesity and diabetes are linked to metabolic dysfunction and inflammation.
- The RXR agonist UAB126 previously showed potential in managing blood glucose and lipid metabolism in obese mice.
- Diabetic retinopathy (DR) is a serious complication of diabetes affecting vision.
Purpose of the Study:
- To evaluate the efficacy of UAB126 in mitigating diabetic retinopathy progression in rodent models.
- To investigate the impact of UAB126 on retinal function and metabolic pathways in diabetes.
Main Methods:
- UAB126 was administered orally or topically to rodent models of type 1 and type 2 diabetes.
- Retinal function was assessed using electroretinography (ERG).
- Gene and protein expression, macrophage glycolysis, and glucose uptake were analyzed.
Main Results:
- UAB126 treatment reduced hyperglycemia and preserved retinal function (ERG amplitudes) in diabetic mice.
- UAB126 improved glycolysis and glucose uptake in diabetic bone marrow-derived macrophages (BMDMs).
- Topical UAB126 increased Rxr and Ppar expression and modulated lipid metabolism genes in retinas.
Conclusions:
- RXR activation with UAB126 demonstrates therapeutic benefits in preclinical models of diabetic retinopathy.
- UAB126 positively impacts glucose metabolism and retinal health in diabetic conditions.
- Targeting RXR pathways offers a potential strategy for managing DR complications.
