TY - JOUR
T1 - Response of experimental retinal neovascularization to thiazolidinediones
AU - Murata, Toshinori
AU - Hata, Yasuaki
AU - Ishibashi, Tatsuro
AU - Kim, Sarah
AU - Hsueh, Willa A.
AU - Law, Ronald E.
AU - Hinton, David R.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035013061&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035013061&partnerID=8YFLogxK
U2 - 10.1001/archopht.119.5.709
DO - 10.1001/archopht.119.5.709
M3 - Article
C2 - 11346398
AN - SCOPUS:0035013061
SN - 2168-6165
VL - 119
SP - 709
EP - 717
JO - JAMA Ophthalmology
JF - JAMA Ophthalmology
IS - 5
ER -
