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 P1 (
adenosine) and P2 (
nucleotide) receptors in Müller glial cells of the mammalian retina. Mammalian Müller cells express various subtypes of
adenosine receptors and metabotropic P2Y receptors. Human Müller cells also express ionotropic P2X(7) receptors. Müller 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 Müller 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 Müller cells. In normal
retinal information processing, Müller 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 Müller cells may have clinical importance, e.g., for the clearance of
retinal edema and for the inhibition of dysregulated cell proliferation in proliferative retinopathies.