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Toshinori Murata, MD; Yasuaki Hata, MD; Tatsuro Ishibashi, MD; Sarah Kim, BS; Willa A. Hsueh, MD; Ronald E. Law, PhD; David R. Hinton, MD

Arch Ophthalmol. 2001;119:709-717.

Objective  To determine the effect of thiazolidinediones (TZDs) on experimental retinal neovascularization.

Methods  The ability of the TZDs troglitazone and rosiglitazone maleate (1-20 µmol/L) to inhibit retinal endothelial cell (REC) proliferation, migration, tube formation, and signaling was determined in response to vascular endothelial growth factor (VEGF). In vivo studies were performed using the oxygen-induced ischemia model of retinal neovascularization. Neonatal mice were treated with intravitreous injection of 0.5 µL of troglitazone (100 µmol/L) or rosiglitazone maleate (100 µmol/L), or vehicle, and retinal neovascularization was assayed qualitatively and quantitatively by means of angiography and histological examination.

Results  Expression of the TZD receptor, peroxisome proliferator-activated receptor , was confirmed in RECs by means of Western immunoblotting. Rosiglitazone and troglitazone inhibited VEGF-induced migration (P<.05), proliferation (P<.05), and tube formation (P<.01) by RECs in vitro beginning at 10 µmol/L. Rosiglitazone and troglitazone inhibited phosphorylation of extracellular signal-regulated mitogen-activated protein kinase 1 in RECs. Intravitreous injection of rosiglitazone or troglitazone inhibited development of retinal neovascularization (P<.01) but did not significantly inhibit VEGF overexpression in the ganglion cell layer of the ischemic retina.

Conclusion  The TZDs inhibit experimental retinal neovascularization with an effect that is primarily downstream of VEGF expression.

Clinical Relevance  The TZDs are widely prescribed and should be evaluated for their potential to inhibit the progression of diabetic retinopathy.

From the Departments of Ophthalmology (Dr Murata) and Pathology (Dr Hinton), Keck School of Medicine of the University of Southern California, Doheny Eye Institute (Dr Hinton), and the Division of Endocrinology, Diabetes and Hypertension, University of California–Los Angeles (Ms Kim and Drs Hsueh and Law), Los Angeles, Calif; and the Department of Ophthalmology, Kyushu University, Fukuoka, Japan (Drs Murata, Hata, and Ishibashi). Dr Hsueh has received honoraria from SmithKline Beecham and Dr Law, from Warner-Lambert/Parke-Davis.

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