Abstract

DO.09.04

Role of Müller cells in retinal neovascularization

Wolfram Eichler

Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Leipzig, Leipzig

Objective
Retinal neovascularization is a serious complication of sight-threatening diseases such as retinal vein occlusion, retinopathy of prematurity, and diabetic retinopathy. To aid understanding of whether Müller cells, the major retinal glial cells, play an essential role in regulating angiogenesis in the retina, various experiments were performed in vitro.
Methods
Standard methods of molecular and cell biology were applied, for example,  culture of primary and indefinitely growing cells, Real-Time PCR, ELISA, Western Blotting and immunohistochemistry.
Results
Under physiological conditions Müller cells determine an anti-proliferative milieu for vascular endothelial cells through the secretion of anti-angiogenic factors including TGF-b, thrombospondin-1, and PEDF. Although hypoxia and glucose deprivation in Müller cells may induce expression of VEGF the levels of this factor are inappropriate to overcome this anti-angiogenic barrier. However, stimulation of endothelial proliferation might be promoted by a surplus of VEGF or bFGF released from additional cellular sources. Müller cells are capable of adjusting secretion of angioregulatory factors according to the demands of changing oxygen tensions and, through secretion of PEDF, they presumably provide an important molecular switch allowing both the control of angiogenesis and neuronal survival. PEDF levels become adjusted according to the severity of hypoxia, either being downregulated and thus facilitating angiogenesis in mild hypoxic conditions (if VEGF levels are modestly elevated) or rise, to allow neuroprotection under strong hypoxia.
Conclusions
Müller cells secrete a variety of soluble mediators which are critically involved in controlling the `angiogenic balance` in the retina. The features described here disclose Müller cells as an important element of cellular homeostasis.

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