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J.J. Wang, S.X. Zhang, J.–X. Ma; Reciprocal regulation between PEDF and VEGF in retinal cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1898.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Angiogenesis is controlled by the balance between angiogenic stimulators such as vascular endothelial growth factor (VEGF) and angiogenic inhibitors such as pigment epithelial derived factor (PEDF). Here we hypothesize that there is a reciprocal regulation between PEDF and VEGF in gene expression in certain cell types in the retina, and this regulation contributes to maintaining their delicate balance. Methods: Bovine retinal endothelial cell (BRCEC) was isolated and cultured for experiment until passages 6. Cobalt chloride (CoCl2 100–1600 µM) or low O2 concentration (<1%) was applied for 24 h to induce hypoxia. PEDF (10–640 nM) and VEGF (10–80 ng/ml) were used in the experiment. Cell viability was analyzed by MTT assay. Intracellular VEGF and PEDF levels were determined by Western blot analysis and normalized by ß–actin levels. VEGF and PEDF secreted into the media were measured by ELISA. Results: Under normal conditions, PEDF of concentrations 10–640 nM inhibited the growth of BRCEC and down–regulated intracellular VEGF expression in a dose–dependent manner. Under hypoxia (induced by low O2 concentration or 100–1600 µM CoCl2), VEGF levels in BRCEC were significantly increased. A low dose of PEDF (10 nM) inhibited the overexpression of VEGF under hypoxia. VEGF at concentrations 10–80 ng/ml down–regulated PEDF expression and secretion in BRCEC. However, in retinal Müller cells this reciprocal regulation of PEDF and VEGF is not as significant as that in BRCEC, indicating that the balance between PEDF and VEGF may be cell–type specific. In vivo study showed that intravitreal injection of PEDF in a rat model of oxygen–induced retinopathy significantly decreased VEGF expression in the retina. Conclusions: There exists a reciprocal regulation of VEGF and PEDF in vascular endothelial cell. This reciprocal regulation may contribute to the maintenance of the balance between angiogenic stimulators and inhibitors, and to the regulation of angiogenesis.
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