PPARγ Agonists: Potential as Therapeutics for Neovascular Retinopathies

The angiogenic, neovascular proliferative retinopathies, proliferative diabetic retinopathy (PDR), and age-dependent macular degeneration (AMD) complicated by choroidal neovascularization (CNV), also termed exudative or "wet" AMD, are common causes of blindness. The antidiabetic thiazolidinediones (TZDs), rosiglitazone, and troglitazone are PPARgamma agonists with demonstrable antiproliferative, and anti-inflammatory effects, in vivo, were shown to ameliorate PDR and CNV in rodent models, implying the potential efficacy of TZDs for treating proliferative retinopathies in humans. Activation of the angiotensin II type 1 receptor (AT1-R) propagates proinflammatory and proliferative pathogenic determinants underlying PDR and CNV. The antihypertensive dual AT1-R blocker (ARB), telmisartan, recently was shown to activate PPARgamma and improve glucose and lipid metabolism and to clinically improve PDR and CNV in rodent models. Therefore, the TZDs and telmisartan, clinically approved antidiabetic and antihypertensive drugs, respectively, may be efficacious for treating and attenuating PDR and CNV humans. Clinical trials are needed to test these possibilities.