Role of Peroxisome Proliferator-Activated Receptorγin Ocular Diseases

Abstract

Peroxisome proliferator-activated receptor γ (PPAR γ), a member of the nuclear receptor superfamily, is a ligand-activated transcription factor that plays an important role in the control of a variety of physiological processes. The last decade has witnessed an increasing interest for the role played by the agonists of PPAR γ in antiangiogenesis, antifibrosis, anti-inflammation effects and in controlling oxidative stress response in various organs. As the pathologic mechanisms of major blinding diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), keratitis, and optic neuropathy, often involve neoangiogenesis and inflammation- and oxidative stress-mediated cell death, evidences are accumulating on the potential benefits of PPAR γ to improve or prevent these vision threatening eye diseases. In this paper we describe what is known about the role of PPAR γ in the ocular pathophysiological processes and PPAR γ agonists as novel adjuvants in the treatment of eye diseases.

Meibomian Gland Disease

“…34 Moreover, as down regulation of the PPAR pathway is seen in MGD as described above, therapeutically targeting this pathway through agonists such as pharmaceuticals (thiazolidinediones: pioglitazone, troglitazone, and rosiglitazone) or dietary supplements (conjugated linoleic acid [vegetables, fruits, nuts, grains and seeds; linseed oil] or docosahexaenoic acid (DHA) may prove to be beneficial. 37,38 …”

A2E induces the transactivation of RARs, PPARs and RXRs and its effects are counteracted by norbixin in retinal pigment epithelium cells in vitro

“…Altogether, here we report that A2E effects on RPE cell death, cytokine regulation, and angiogenesis, which are all important during AMD pathophysiology, may be controlled at least partly through RARs, RXRs and PPARs modulation. We are not the firsts to point out the potential importance of NRs and particularly, PPARs in controlling several AMD-pathogenic pathways (46)(47)(48)(49)(50)(51). Indeed, it has been shown that PPAR-a agonists protect RPE cells from an oxidative stress insult in vitro (52) and reduce angiogenesis in mouse models of neovascular AMD (53).…”

The C161T Polymorphism in Peroxisome Proliferator-Activated Receptor <i>ɣ</i>2, but Not Pro12Ala, Is Associated with Diabetic Retinopathy in Type 2 Diabetes Mellitus in an Egyptian Population

“…In fact, the PPARγ agonists (thiazolidinediones, TZDs) currently used for the treatment of insulin resistance are now perceived as novel adjuvant in treatment of ocular diseases. Owing to their anti-inflammatory, anti-atherogenic, neuroprotective, and antioxidative effects, TZDS may have therapeutic potential in diabetic microvascular complications such as DR [45]. But still the undesirable side effects of TZDs should be weighed against their protective role.…”