Response of experimental retinal neovascularization to thiazolidinediones

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

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

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, pemxisome proliferator-activated receptor γ, 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.

Original languageEnglish
Pages (from-to)709-717
Number of pages9
JournalArchives of Ophthalmology
Volume119
Issue number5
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Ophthalmology

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