Vascular Endothelial Cell Growth Inhibitor of Normal and Pathologic Human Vitreous

Jacobson, Bernard; Basu, P. K.; Hasany, S. M.

doi:10.1001/archopht.1984.01040031259031

Cited by 25 publications

(9 citation statements)

References 12 publications

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“…Multiple angiogenic stimulators and inhibitors are expressed in the retina and vascular cells (28,29). Insulin-like growth factor-1 has been shown to regulate the expression of VEGF in RPE cells (30), suggesting that regulatory interactions exist among angiogenic stimulators.…”

Section: Figsupporting

confidence: 40%

Down-regulation of Vascular Endothelial Growth Factor and Up-regulation of Pigment Epithelium-derived Factor

Gao

Gee

et al. 2002

Journal of Biological Chemistry

120

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We have previously shown that intravitreal injection of plasminogen kringle 5 (K5), a potent angiogenic inhibitor, inhibits ischemia-induced retinal neovascularization in a rat model. Here we report that K5 downregulates an endogenous angiogenic stimulator, vascular endothelial growth factor (VEGF) and up-regulates an angiogenic inhibitor, pigment epithelium-derived factor (PEDF) in a dose-dependent manner in vascular cells and in the retina. The regulation of VEGF and PEDF by K5 in the retina correlates with its anti-angiogenic effect in a rat model of ischemia-induced retinopathy. Retinal RNA levels of VEGF and PEDF are also changed by K5. K5 inhibits the p42/p44 MAP kinase activation and nuclear translocation of hypoxia-inducible factor-1␣, which may be responsible for the down-regulation of VEGF. Down-regulation of endogenous angiogenic stimulators and up-regulation of endogenous angiogenic inhibitors, thus leading toward restoration of the balance in angiogenic control, may represent a mechanism for the anti-angiogenic activity of K5.

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Section: Figsupporting

confidence: 40%

Down-regulation of Vascular Endothelial Growth Factor and Up-regulation of Pigment Epithelium-derived Factor

Gao

Gee

et al. 2002

Journal of Biological Chemistry

120

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“…The retina and vitreous fluid contain endogenous angiogenic inhibitors [7,8,9,10,11]. PEDF, a serine proteinase inhibitor (serpin), has been identified as a potent angiogenic inhibitor endogenously expressed in the retina [12].…”

supporting

confidence: 44%

Kallikrein-binding protein inhibits retinal neovascularization and decreases vascular leakage

et al. 2003

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Aims/hypothesis. Kallikrein-binding protein (KBP) is a serine proteinase inhibitor (serpin). It specifically binds to tissue kallikrein and inhibits kallikrein activity. Our study was designed to test its effects on retinal neovascularization and vascular permeability. Angiogenesis in the retina is controlled by a delicate balance between angiogenic stimulators (e.g., vascular endothelial growth factor, VEGF) and angiogenic inhibitors (e.g., pigment epithelium-derived factor, PEDF) [1,2,3]. Under certain pathological conditions such as diabetic retinopathy and retinopathy of prematurity (ROP), the retinal cells increase the production of angiogenic stimulators while decreasing angiogenic inhibitors in response to local hypoxia [4,5]. These changes break the balance in angiogenesis control and consequently, resulting in over-proliferation of capillary endothelial cells and retinal neovascularization which is a common cause of blindness [2,3,6]. The molecular mechanism leading to retinal neovascularization is presently not known. Methods. Endothelial cell proliferation was deter

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“…It has also been reported that the early events of cell proliferation are dependent on continuous protein synthesis and that a 50-70% inhibition of protein synthesis effectively inhibits cell growth (Pardee, 1989). The VH has been shown to contain growth inhibitors for endothelial cells (Jacobson et al, 1984;Lisnayk, 1988). Thus far the effects of VH factor(s) on lens epithelial cell division have not been examined.…”

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confidence: 42%

Growth regulation of the mammalian ocular lens by vitreous humor

Banerjee

Parafina

Bagchi

1992

J of Cellular Biochemistry

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Experiments were performed in our laboratory to study the effects of a mammalian 8 kD vitreous humor (VH) factor on the DNA synthesis and mitosis of the epithelial cells of organ cultured rabbit lens. The 8 kD polypeptide factor was purified from mature rabbit vitreous humor by liquid chromatography. Proliferative activities of the epithelial cells of organ cultured lenses were stimulated by 3% rabbit serum. The data from our experiments depicted that the 8 kD VH factor effectively inhibits DNA synthesis and mitosis by the epithelial cells of the organ cultured lens. Our experiments also showed that this 8 kD VH factor can maintain its growth inhibitory activity even when heated for 3 min at 95 degrees C. The growth inhibitory effect of the 8 kD VH factor was dose dependent. Using iodinated vitreal proteins it was demonstrated that the VH proteins are able to enter or bind to lens epithelial cells. The growth inhibitory effect of the 8 kD VH factor was also tested on tissue cultured lens epithelial cells. These experiments showed that the 8 kD VH factor has no growth inhibitory effect on the tissue cultured lens epithelial cells. This experiment has been repeated many times using different concentrations of the factor. These observations suggest that the 8 kD VH factor may have receptors in the lens capsular material (extracellular matrix) and the factor-receptor binding is essential for the growth inhibitory effect.

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Vascular Endothelial Cell Growth Inhibitor of Normal and Pathologic Human Vitreous

Cited by 25 publications

References 12 publications

Down-regulation of Vascular Endothelial Growth Factor and Up-regulation of Pigment Epithelium-derived Factor

Down-regulation of Vascular Endothelial Growth Factor and Up-regulation of Pigment Epithelium-derived Factor

Kallikrein-binding protein inhibits retinal neovascularization and decreases vascular leakage

Growth regulation of the mammalian ocular lens by vitreous humor

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