Regulation of vascular endothelial growth factor and pigment epithelium-derived factor in rat retinal explants under retinal acidification

Purpose To explore whether retinal acidification independently regulates the production of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) and whether the regulation is related to oxidative stress. Methods After culture of rat retinas in the medium with normal pH (7.2) or acidic pH (6.8 or 6.5), or followed by pH reversion back to the normal, or meanwhile with the presence of antioxidants, VEGF and PEDF mRNA and protein were determined by quantitative real-time reverse transcription-ploymerase chain reaction and western blot. Results Retinal acidification significantly increased the expression of VEGF and PEDF mRNA and protein. pH reversion recovered VEGF and PEDF mRNA and reduced VEGF and PEDF protein induced by acidification. Acidification-increased VEGF was completely inhibited in the retinas of pH 6.8, and largely reduced in the retinas of pH 6.5 by antioxidants. Antioxidants further increased PEDF mRNA and protein induced by retinal acidification. Conclusions VEGF can be induced by retinal acidification alone, which may be regulated through oxidative stress, among other factors. The fact that increased PEDF under retinal acidification is promoted by antioxidants suggests that oxidative stress inhibits the production of PEDF. Eye (2009) 23, 2105-2111; doi:10.1038/eye.2009.161; published online 3 July 2009