S64 receptor (#APR-018) antibodies in immunofluorescence studies, it was found that noise-induced upregulation of P2Y6 receptors in the spiral ganglion neurons further supports the involvement of NTPDase5 in regulating P2Y receptor signaling. Noise stress also induced P2Y14 receptor expression in the root processes of the outer sulcus cells, but this was not associated with the localization of the E- NTPDases. P2Y receptors in the eye In the postnatal and mature retina, many processes are controlled by the action of nucleotides. Their effects are partly mediated via the activation of metabotropic P2Y receptors. However, little is known about the developmen- tal regulation and cellular localization of P2Y receptor subtypes in the retina. Immunohistochemical and neurophysiological methods [12] demonstrated that purinergic signaling via P2Y1 and P2Y4 receptors might contribute to differentiation processes in the postnatal retina. Immunostaining adult rat retina for P2Y2, P2Y4, and P2Y6 receptors showed that P2Y4 expression overlapped with the Müller cell marker, cellular retinaldehyde-binding protein (CRALBP; Fig. 1). P2Y4 was expressed predominantly in Müller cell end-feet (Fig. 1b). Punctuate structures, forming a small band in the inner plexiform layer (IPL), potentially representing synapses, showed an intense staining for P2Y4, too. P2Y2 (Fig. 1a) and P2Y6 (Fig. 1c) expression was largely restricted to retinal neurons such as ganglion cells and cells of the inner nuclear layer (INL). Immunohistochemical staining using anti-P2Y4 receptor antibody showed indisputable expres- sion of P2Y4, detectable only after the third postnatal week (P20). Intense neuronal activity in the sensory retina is associated with a volume increase of neuronal cells and a decrease in the osmolarity of the extracellular space fluid. Wurm et al. [13] further showed the existence of an endogenous purinergic mechanism that prevented hypo- osmotic swelling of retinal glial (Müller) cells in mice. They suggested that autocrine/paracrine activation of purinergic receptors via UTP and enzymes is crucially involved in the regulation of the glial cell volume. By using anti-P2Y4 receptor antibody in immunohistochem- istry experiments, they showed that P2Y4 immunolabeling was localized to the somata of retinal neurons, but not glial cells, while in other retinal layers, UTP may be more directly involved in the regulation of glial cell volume, as indicated by the co-localization of P2Y4 labeling and CRALBP (Fig. 1d). The expression of various P2Y receptor subtypes has been demonstrated in the retina, but the localization of P2Y Purinergic Signalling (2012) 8 (Suppl 1):S61–S79 receptors and their role in retinal signaling remain unclear. The major findings of the study conducted by Ward et al. [14] are that P2Y4 receptors are heavily expressed within the inner retina, particularly within the dendrites and axon terminals of rod bipolar cells and in cells postsynaptic to cone bipolar cells, as demonstrated in Western blot and immunocytochemistry methods using anti-P2Y4 receptor antibody. Moreover, altering neural activity with light altered P2Y4 expression within rod bipolar cell axon terminals, and injection of the agonist UTP caused a substantial reduction in the amplitude of the rod and cone post-receptoral response (PII), indicating further evidence for purines in retinal processing. Detachment of the neural retina from the pigment epithelium causes, in addition to photoreceptor deconstruc- tion and neuronal cell remodeling, an activation of glial cells. It has been suggested that gliosis contributes to the impaired recovery of vision after reattachment surgery that may involve both formerly detached and non-detached retinal areas. Müller and microglial cell reactivity was monitored in a porcine model of rhegmatogenous retinal detachment to determine whether gliosis is present in detached and non-detached retinal areas. The results demonstrated that distinct symptoms of Müller cell gliosis were not only restricted to the detached retinal areas but occurred also in non-detached retinal regions of the surgical eyes. Furthermore, among physiological changes, the immunoreactivities for P2Y1 (Fig. 2, left panel) and P2Y2 (Fig. 2, middle panel), but not P2Y4 (Fig. 2, right panel) receptor proteins, apparently increased only in detached areas [15]. Extracellular ATP has been shown to mobilize intracel- lular calcium in cultured ovine lens epithelial cells and in human lens epithelium, suggesting a role for purines in the modulation of lens transparency. The expression profiles of P2Y receptor isoforms were characterized throughout the rat lens at both the molecular and the functional levels [16]. The epithelium does not express P2Y1 and P2Y2, but the underlying fiber cells, which differentiate from the epithe- lial cells, exhibit strong membranous labeling. P2Y1 expression extended deeper into the lens compared with P2Y2, and its expression co-localized with Cx50 gap junction plaques, while P2Y2 did not. Immunohistochem- istry using isoform-specific anti-P2Y4 receptor and anti- P2Y6 receptor antibodies indicated that P2Y4 and P2Y6 receptors were observed in both epithelial cells and fiber cells, but the labeling was predominantly cytoplasmic in nature. The inability of UTP and UDP to mobilize intracellular calcium in the epithelium and the predominantly cytoplasmic location of P2Y4 and P2Y6 suggest that these receptors may represent an inactive pool of receptors that may be activated under non-physiological conditions. In contrast, their results indicated that P2Y1 and P2Y2 are functionally active in fiber