Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential

Barnstable, Colin J.; Tombran-Tink, Joyce

doi:10.1016/j.preteyeres.2004.05.002

Cited by 216 publications

(166 citation statements)

References 67 publications

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“…Alterations in the balance between antiangiogenic and angiogenic growth factors such as VEGF and PEDF may increase or decrease susceptibility to retinal angiogenesis. 17,38 In patients with retinal neovascularization, decreased levels of PEDF protein in vitreous were found compared to that of controls. 39 Among diabetic patients with no or mild retinopathy, those with decreased levels of PEDF in aqueous humor collected at cataract surgery developed progressive retinopathy at increased rates by the time of follow-up compared to nonprogressors and control patients.…”

Section: Discussionmentioning

confidence: 98%

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Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization

Chan

Pham

Zhou

et al. 2005

Laboratory Investigation

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Clinical observations suggest that genetic factors may influence heterogeneity of angiogenic responses in cardiovascular disease, proliferative diabetic retinopathy, and neoplasia. Experiments among mouse strains using a corneal micropocket assay indicate that extent of angiogenesis may be genetically determined. Here, we established the strain-dependence of hypoxia-induced retinal angiogenesis in multiple mouse strains which paralleled the rank order found for bFGF-induced corneal angiogenesis. Using quantitative real-time RT-PCR, strain-related gene expression differences in retina/choroid between C57BL/6J and 129S3/SvIM, inbred strains with relatively low and high levels of angiogenesis, respectively, after 0, 6, 12, 24, 48, and 96 h hypoxia were determined for vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), angiogenic ligands potently induced by hypoxia, and for pigment epithelium-derived factor (PEDF) and thrombospondin-1 (TSP-1), endogenous broad-spectrum antiangiogenic factors. Indirect ELISA was used to correlate VEGF and PEDF protein levels with mRNA expression. At the onset of hypoxia, both PEDF and TSP-1 levels were increased over 15-fold and VEGF was increased over 10-fold compared to Ang-2 in both strains. At the onset of neovascularization (48 h), both VEGF and Ang-2 mRNA levels were increased in the more angiogenic 129S3/ SvIM strain (Po0.02), which was not observed among developmental control animals. PEDF expression was higher in the less angiogenic C57BL/6J strain at 6, 12, 24, and 96 h hypoxia (Po0.03), while TSP-1 expression was higher in C57BL/6J throughout the entire time course of hypoxia (4 days) compared to 129S3/SvIM (Po0.02). Among developmental control animals, PEDF and TSP-1 expression was also increased at P14 and P16 in C57BL/6J strain compared to 129S3/SvIM (Po0.02). Strain-dependent expression of both pro-and antiangiogenic growth factors may determine heterogeneity in the angiogenic response and potentially, susceptibility to angiogenesis-dependent diseases.

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Section: Discussionmentioning

confidence: 98%

“…12,13 Natural inhibitors of angiogenesis include endostatin, angiostatin, pigment epithelium-derived factor (PEDF), and thrombospondin-1 (TSP-1). [14][15][16][17] Genetic influences on the regulation of pro-and antiangiogenic factors may provide a potential mechanism for strain-related heterogeneity in the angiogenic response.…”

mentioning

confidence: 99%

Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization

Chan

Pham

Zhou

et al. 2005

Laboratory Investigation

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“…PEDF is mainly secreted by retinal pigment epithelial cells in the eye, as well as by other body tissues [32]. Apart from its neurotrophic and neuroprotective properties, there is growing evidence to suggest that PEDF is among the most important natural inhibitors of angiogenesis, and that it is the main factor accounting for the anti-angiogenic activity of the vitreous fluid, where it is found in abundant quantities [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…Apart from its neurotrophic and neuroprotective properties, there is growing evidence to suggest that PEDF is among the most important natural inhibitors of angiogenesis, and that it is the main factor accounting for the anti-angiogenic activity of the vitreous fluid, where it is found in abundant quantities [32,33]. The relevance of PEDF to human neovascular disease is supported by studies showing that decreased levels of PEDF in the vitreous are associated with PDR [15,16].…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

Garcia-Ramírez

Canals

Hernández³

et al. 2007

Diabetologia

151

135

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Aims/hypothesis The aim of this study was to compare the protein profile of vitreous fluid from diabetic patients with proliferative diabetic retinopathy (PDR) with that from nondiabetic patients with idiopathic macular holes (MH). The mRNA of proteins differentially produced was also assessed in the retinas from diabetic and non-diabetic donors. Materials and methods Vitreous humour from type 1 diabetic patients with PDR (n=8) and from non-diabetic patients with MH (n=10) closely matched in terms of age were studied. The comparative proteomic analysis was performed using fluorescence-based difference gel electrophoresis (DIGE). Differentially produced proteins (abundance ratio >1.4, p<0.05) were identified by mass spectrometry. Expressions of mRNA were measured by real-time RT-PCR in retinas from ten human eyes obtained at post-mortem (five eyes from diabetic subjects and five eyes from non-diabetic subjects). Results Eight proteins were highly produced in PDR patients in comparison with non-diabetic subjects: zinc-α 2 -glycoprotein (ZAG), apolipoprotein (apo) A1, apoH, fibrinogen A, and the complement factors C3, C4b, C9 and factor B). We found three proteins that were underproduced in PDR subjects: pigment epithelial derived factor (PEDF), interstitial retinol-binding protein (IRBP) and inter-α-trypsin inhibitor heavy chain (ITIH2). There was no overlap in the vitreous levels of the above-mentioned proteins between PDR patients and non-diabetic control subjects. The differential production of ZAG, C3, factor B, PEDF and IRBP was further confirmed by western blot, and was in agreement with mRNA levels detected in the retina. Conclusions/interpretation Proteomic analysis by DIGE, which permits an accurate quantitative comparison, was useful in identifying new potential candidates involved in the pathogenesis of PDR.

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“…Pigment epithelium-derived factor (PEDF) 3 is an important protein for the survival and function of the retina (1)(2)(3). This factor is secreted apicolaterally from the retinal pigment epithelium to act on photoreceptor morphogenesis, retinal neuroprotection, and neurite outgrowth (4 -8).…”

mentioning

confidence: 99%

Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

Subramanian

Locatelli-Hoops

Kenealey

et al. 2013

Journal of Biological Chemistry

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Background: PEDF has neurotrophic activity and interacts with PEDF-R, a membrane-linked lipase. Results: A PEDF-binding region of PEDF-R is required for PEDF-R enzymatic stimulation, and peptides derived from this region block PEDF⅐PEDF-R-mediated retinal survival activities. Conclusion: A ligand binding domain is identified in PEDF-R, a critical receptor for the survival activity of PEDF. Significance: The findings provide mechanistic insight into the survival activity of PEDF.

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Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential

Cited by 216 publications

References 67 publications

Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization

Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

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