Journal
PROGRESS IN RETINAL AND EYE RESEARCH
Volume 30, Issue 5, Pages 324-342Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.preteyeres.2011.06.001
Keywords
ATP; Adenosine; Ecto-nucleotidase; Edema; Proliferation; Muller Cell; Retina
Categories
Funding
- Deutsche Forschungsgemeinschaft [RE 849/12, GRK 1097/1, KO 1547/6]
- German Federal Ministry of Education and Research (BMBF) [DLR/01GZ0703, 0313909]
- Fundacion BBVA, Spain
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Purines (in particular, ATP and adenosine) act as neuro- and gliotransmitters in the sensory retina where they are involved in bidirectional neuron-glia signaling. This review summarizes the present knowledge about the expression and functional importance of 131 (adenosine) and P2 (nucleotide) receptors in Muller glial cells of the mammalian retina. Mammalian Muller cells express various subtypes of adenosine receptors and metabotropic P2Y receptors. Human Muller cells also express ionotropic P2X(7) receptors. Muller cells release ATP upon activation of metabotropic glutamate receptors and/or osmotic membrane stretching. The osmotic mechanism is abrogated under conditions associated with ischemia-hypoxia and inflammation, resulting in swelling of the Muller cells when the extracellular milieu is hypoosmotic. However, exogenous glutamate, which induces the release of ATP and adenosine, and thus activates P2Y(1) and A(1) adenosine receptors, respectively, prevents such osmotic swelling under pathological conditions, suggesting unimpaired receptor-induced release of ATP. In addition to the inhibition of swelling, which is implicated in regulating the volume of the extracellular space, purinergic signaling is involved in mediating neurovascular coupling. Furthermore, purinergic signals stimulate the proliferation of retinal precursor cells and Muller cells. In normal retinal information processing, Muller cells regulate the synaptic activity by the release of ATP and adenosine. In retinopathies, abrogation of the osmotic release of ATP, and the upregulation of ecto-apyrase (NTPDase1), may have neuroprotective effects by preventing the overactivation of neuronal P2X receptors that are implicated in apoptotic cell death. Pharmacological modulation of purinergic receptors of Muller cells may have clinical importance, e.g., for the clearance of retinal edema and for the inhibition of dysregulated cell proliferation in proliferative retinopathies. (C) 2011 Elsevier Ltd. All rights reserved.
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