Abstract
Abstract: :
Purpose: Signal transducer and activator of transcription protein 3 (STAT3) is a transcription factor that is activated by vascular endothelial growth factor. It participates in many biological processes, including tumor angiogenesis. To evaluate the possible role of STAT3 in retinal vascular diseases, we investigated the expression and activation of STAT3 in a mouse model of ischemia–induced retinal neovascularization. Methods:To produce retinal neovascularization mice were subjected to hyperoxia from post natal day 7 (p7) to p12 and then returned to room air for up to 10 days. RNA was isolated from oxygen–exposed and normal control retinae at p12, p15 and p18. The relative levels of STAT3 mRNA were determined by semi–quantitative RT–PCR. Retinal protein was isolated at p12, p15, p18 and p22. STAT3 protein levels and the levels of the activated form of STAT3 (pSTAT3) were determined by immunoblotting. STAT3 and pSTAT3 were demonstrated by immunofluorescence in sections of neovascularized and normal retinae at p12, p15 and p18. Results:STAT3 mRNA and protein levels were elevated in the neovascularized retina on p18, when neovascularization is maximal. Activated STAT3 was demonstrated in protein isolates from the neovascularized retina on p18, but not in other retinal samples. STAT3 partially colocalized with blood vessels and the specific STAT3 staining increased between p12 and p18. pSTAT3 colocalized completely with retinal blood vessels, and was more strongly associated with the pathological epiretinal vessels than with inner retinal vessels. Conclusions:The level of STAT3 expression increased, and activation of STAT3 was observed in association with oxygen–induced neovascularization. In addition, activated pSTAT3 was preferentially localized to neovascular retinal vessels. These data suggest that STAT3 may have a role in proliferative retinopathy.
Keywords: retinal neovascularization • retinopathy of prematurity • transcription factors