Role of pigment epithelium-derived factor (PEDF) on arsenic-induced neuronal apoptosis

The detection of pigment-epithelium-derived factor (PEDF) in corneal tissue has allowed greater understanding of the avascularity of corneal tissue. The ability of the cornea to maintain the avascular nature of this tissue, also referred to as the angiogenic privilege of the cornea, could be partly attributed to the presence of this factor. This privilege is severely impaired by various diseases of the ocular surface associated with inflammation and infection that are often followed by neovascularisation, which compromises the transparency of the cornea and results in visual impairment. The rapidly increasing insights into the basic mechanisms controlling neovascularisation, i.e. balance of growth factor activation and enzymatic activity, has most recently led to the development of large-scale use of specific antiangiogenic agents in the treatment of neovascular age-related macular degeneration (AMD). Focusing on the effects of vascular endothelial growth factor (VEGF), the use of such agents, including bevacizumab (Avastin®), a humanised anti-VEGF monoclonal antibody originally used in the treatment of metastatic colorectal cancer, has been investigated in corneal angiogenesis. PEDF is only one of the many factors involved in ocular angiogenesis. However, although it is only a small protein, it has strong antiangiogenic actions that are expressed in the retinal pigment epithelial (RPE) layer, as well as in other parts of the eye. There are specific characteristics that could designate a special role for PEDF in the regulation of avascularity in the eye. In this article, we focus on corneal angiogenesis and highlight the special features of this somewhat unexplored cytokine, outlining the current knowledge and possible role of PEDF in corneal neovascularisation.

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Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00046.2014 ◽

2014 ◽

Vol 306 (12) ◽

pp. E1367-E1377 ◽

Cited By ~ 10

Author(s):

Thomas V. Lakeland ◽

Melissa L. Borg ◽

Maria Matzaris ◽

Amany Abdelkader ◽

Roger G. Evans ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Expenditure ◽

Body Mass ◽

Pigment Epithelium ◽

In Vivo Studies ◽

Whole Body ◽

Pigment Epithelium Derived Factor ◽

Metabolic Role

Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo.

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