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Response of experimental retinal neovascularization to thiazolidinediones
T Murata1, Y Hata, T Ishibashi
1Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Objective:
To determine the effect of thiazolidinediones (TZDs) on experimental retinal neovascularization.
Methods:
The ability of the TZDs troglitazone and rosiglitazone maleate (1-20 micromol/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 microL of troglitazone (100 micromol/L) or rosiglitazone maleate (100 micromol/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 gamma, 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 micromol/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.