Paul Flechsig Institute of Brain Research, University of Leipzig, 04109 Leipzig, Germany.
Prog Retin Eye Res. 2011 Sep;30(5):324-42. doi: 10.1016/j.preteyeres.2011.06.001. Epub 2011 Jun 14.
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.
嘌呤（特别是 ATP 和腺苷）作为神经递质和神经胶质递质在感觉视网膜中发挥作用，参与双向神经元-神经胶质信号传递。本文综述了哺乳动物视网膜 Müller 胶质细胞中 P1（腺苷）和 P2（核苷酸）受体的表达和功能重要性的现有知识。哺乳动物 Müller 细胞表达各种亚型的腺苷受体和代谢型 P2Y 受体。人类 Müller 细胞还表达离子型 P2X(7)受体。Müller 细胞在代谢型谷氨酸受体激活和/或渗透压膜拉伸时释放 ATP。在与缺血缺氧和炎症相关的条件下，该渗透压机制被阻断，导致细胞外环境低渗时 Müller 细胞肿胀。然而，外源性谷氨酸诱导 ATP 和腺苷的释放，从而分别激活 P2Y(1)和 A(1)腺苷受体，在病理条件下可防止这种渗透压肿胀，表明受体诱导的 ATP 释放未受损。除了抑制肿胀（涉及调节细胞外空间的体积）外，嘌呤能信号还参与介导神经血管偶联。此外，嘌呤信号刺激视网膜前体细胞和 Müller 细胞的增殖。在正常视网膜信息处理中，Müller 细胞通过释放 ATP 和腺苷来调节突触活动。在视网膜病变中，ATP 渗透压释放的阻断和外切-apyrase（NTPDase1）的上调，可能通过防止神经元 P2X 受体的过度激活而具有神经保护作用，神经元 P2X 受体与凋亡性细胞死亡有关。Müller 细胞嘌呤能受体的药理学调节可能具有临床意义，例如，清除视网膜水肿和抑制增殖性视网膜病变中失调的细胞增殖。
