by Leigh MacMillan
Diabetic retinopathy, a leading cause of blindness in the United States, is associated with metabolic dysfunction and chronic elevation of retinal inflammation.
Megan Capozzi, PhD, John Penn, PhD, and colleagues previously showed that the transcription factor PPAR-beta/delta can regulate aspects of diabetic retinopathy, including inflammation and angiogenesis (blood vessel growth). They have now used a PPAR-beta/delta inhibitor, GSK0660, to further characterize the protein’s role in human retinal Müller cells, which support retinal neurons, microvascular endothelial cells and mouse retina.
They found that GSK0660 inhibits production of inflammatory mediators by Müller cells and blocks the effects of one of those mediators, TNF-alpha, on leukocyte adhesion in endothelial cells and mouse retina.
The results, reported in the January issue of Experimental Eye Research, show that inhibition of PPAR-beta/delta reduces both Müller cell and endothelial cell inflammatory signaling events. Because PPAR-beta/delta inhibition targets multiple pathogenic steps in diabetic retinopathy, it may be an ideal therapeutic strategy for the disease, the authors conclude.
This research was supported by the National Institutes of Health (grants EY007533, EY023639, EY008126, DK020593, EY007135, TR000445), Research to Prevent Blindness, Inc. and the Carl Marshall Reeves & Mildred Almen Reeves Foundation, Inc.
