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Peroxisome
proliferator-activated receptor-gamma ligands inhibit choroidal
neovascularization
Murata
T, He S, Hangai M, Ishibashi T, Xi XP, Kim S, Hsueh WA, Ryan SJ, Law RE, Hinton
DR
Department
of Ophthalmology, Doheny Eye Institute, Los Angeles, CA, USA
Purpose.
To determine the antiangiogenic effects of peroxisome proliferator-activated
receptor (PPAR)-gamma agonists on ocular cells involved in the pathogenesis of
choroidal neovascularization (CNV) in vitro and on experimental laser
photocoagulation-induced CNV in vivo.
Methods.
PPAR-gamma expression in human retinal pigment epithelial (RPE) cells and bovine
choroidal endothelial cells (CECs) was determined using an RNase protection
assay and Western blot analysis. Two PPAR-gamma ligands, troglitazone (TRO) and
rosiglitazone (RSG; 0.1-20 microM), were used to assess effects on RPE and CEC
proliferation and migration and CEC tube formation in response to vascular
endothelial growth factor (VEGF).
The effects of intravitreal injection of TRO on laser photocoagulation-induced
CNV lesions in rat eyes (15 experimental, 15 control, nine burns per eye) and
cynomolgus monkey eyes (two experimental, two control, seven paramacular burns
per eye) was assessed by fluorescein angiography and histologic evaluation.
Results.
PPAR-gamma1 was expressed in both RPE and CEC. PPAR-gamma ligands significantly
inhibited VEGF-induced migration and proliferation in both cell types and tube
formation of CEC in a dose-response manner. CNV in rats was markedly inhibited
by intravitreous injection of TRO (P < 0.001).
Lesions showed significantly less fluorescein leakage and were histologically
thinner in the TRO-treated animals.
Similar findings were present in the TRO-treated lesions in two monkey eyes.
The drug showed no apparent adverse effects in the adjacent retina or in control
eyes.
Conclusions.
The inhibition of VEGF-induced choroidal angiogenesis in vitro, and CNV in vivo
by PPAR-gamma ligands suggests the potential application of these agents in the
large group of patients with age-related macular degeneration complicated by CNV.
PMID:
10892878 [PubMed - indexed for MEDLINE]
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