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C. Liu, X. Gu, W.–H. Wang, D. Bingaman; Local Delivery of Anecortave Acetate Inhibits the Expression of Retinal IGF–1/IGF–1 Receptor in the Rat OIR Model . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4135.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Anecortave acetate is an angiostatic cortisene that reproducibly inhibits ocular angiogenesis elicited by numerous stimuli in a variety of species. IGF–1 and its receptor have been implicated in ocular angiogenesis. This study determined the mRNA expression of retinal IGF–1 and IGF–1 receptor following a single intravitreal injection of anecortave acetate in rat model of oxygen–induced retinopathy (OIR) model. Methods: Sprague–Dawley rat pups were placed into oxygen delivery chamber at postnatal day 0, and subjected to a 50/10 oxygen–exposure profile from Day 0 to Day 14 postpartum. Litters were then placed into room air from P14–P20. On P14 pups were randomly assigned into groups receiving bilateral intravitreal injection of 5 µ l 10% anecortave acetate or vehicle, or as nontreated controls. Retinal tissues were harvested at P14 from controls, and on P16 and P20 for both treatment groups. Retinas were isolated by using RNAqueous–4PCR kit.The RNA was then converted into cDNA using TaqMan reverse transcription reagents. The retinal mRNA expression for IGF–1 and IGF–1 receptor was determined by quantitative real–time RT–PCR. Each targeted gene mRNA was then normalized to GAPDH control. Results: mRNA expression of retinal IGF–1 and IGF–1 receptor in vehicle injected–eyes were dramatically increased from P16 to P20 vs. P14 control eyes (Student–Newman–Keuls Method, P<0.001, and P<0.001, respectively). The upregulation IGF–1/IGF–1 receptor expression correlates with the time of maximal preretinal neovascularization observed in the rat OIR model. Retinal IGF–1 and IGF–1 receptor mRNA expression were significantly decreased in eyes injected with 10% anecortave acetate at postnatal day 20 as compared to vehicle–injected eyes in age–matched controls (Student–Newman–Keuls Method; P<0.001 and P=0.001, respectively). The expression level of IGF–1 and IGF–1 receptor was reduced by 36.9% and 50.5%, respectively, in drug treated–eyes at postnatal Day 20. No significant difference was found in the mRNA expression of retinal IGF–1 and IGF–1 receptor between drug–treated eyes and vehicle–treated eyes at postnatal Day 16. Conclusions: Local delivery of anecortave acetate reproducibly inhibits preretinal NV in the rat OIR model, where anecortave has been shown previously to enhance the expression of plasminogen activator inhibitor–1 (PAI–1). Results from the current study indicate that a portion of the robust angiostatic activity of anecortave acetate may be exerted through the suppression of retinal IGF–1 and IGF–1 receptor mRNA in rat OIR model.
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