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

Abstract

Purpose To explore whether retinal acidification independently regulates the production of vascular endothelial growth factor (VEGF) and pigment epitheliumderived 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 realtime 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.

Development of diabetes-induced acidosis in the rat retina

“…Because acidosis can increase VEGF in tumors and the retina (Fukumoto et al, 2012; Shi et al, 2001; Xu et al, 2002; Zhu et al, 2009), one of the interesting questions is whether the acidosis we have observed is partially responsible for VEGF upregulation in diabetes. Proving a connection is difficult, but we and others have found increased VEGF in rats mainly at around 1 month, that is, at just the point of maximum H + , with a decrease after this (Kirwin et al, 2009; Lau et al, 2013; Schrufer et al, 2010), again as we observe in H + .…”

“…First, VEGF, which is acknowledged to be an important player in diabetic retinopathy (Stitt et al, 2015), is known to be upregulated by acidosis independently of hypoxia in glioblastoma (Xu et al, 2002) and pancreatic adenocarcinoma (Fukumura et al, 2001; Shi et al, 2001). VEGF also increases when the isolated rat retina is subjected to acidosis (Zhu et al, 2009). Second, in neonatal retina acidosis can mimic the effect of oxygen-induced retinopathy in causing neovascularization (Holmes et al, 1998, 1999; Leske et al, 2004).…”

Chemical pleurodesis – a review of mechanisms involved in pleural space obliteration

“…There are data showing that pleural thickening, low pH and glucose levels correlate with VEGF secretion into the pleural cavity [109]. There are no data on the influence of pH on VEGF production by PMCs, however there is evidence that low pH increases VEGF production in rat’s retinal extracts [110]. It has been shown that VEGF secretion is largely dependent on TGF-β.…”

Nicotine Increases the VEGF/PEDF Ratio in Retinal Pigment Epithelium: A Possible Mechanism for CNV in Passive Smokers with AMD

“…57 Primer sequences for human PEDF, nAchR ␣3, ␣10 and ␤1 subunits are available in the qPrimerDepot database (http://primerdepot.nci.nih.gov/; NIH, Bethesda, MD). All primer sequences for rat GAPDH and VEGF 58 ; PEDF 59 ; and ␣4, ␣5, ␣7, and ␤2 nAchR 60 were previously published. Primers were purchased from Sigma-Aldrich.…”