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Tracy Ho, Kirstan Vessey, Andrew Jobling, Erica Fletcher; The P2X4 Receptor and NTPDase1/CD39 Enzyme are Expressed in the Mouse Retina and are Up-regulated in Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):730. doi: https://doi.org/.
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ATP and other related purines have been found to act as transmitters at a wide range of purine receptors. Activation of purine receptors has been shown to be important for signaling between neurons and glial cells in the retina. Recently, the purinergic system has been implicated in the mechanisms underlying retinal degeneration (RD). The aim of this study was to characterise the expression of purinergic system components, the P2X4-receptor and NTPDase1, in the wild-type (WT) mouse retina and to determine if gene alterations are associated with RD.
Immunohistochemistry and qPCR were used to assess the cellular localisation and mRNA expression level of the ATP receptor, P2X4, and the enzyme responsible for ATP hydrolysis, NTPDase1, in retinae of adult WT (C57Bl6/J) and rd1 mouse at different ages (P14, P30 and P90) . Pre-embedding immunoelectron microscopy was used to determine the ultrastructural synaptic localisation of the P2X4-R in the WT retina.
P2X4-Rs immunoreactivity (IR) was present as discrete puncta within the synaptic layers of the WT retina and colocalised with neurons important for lateral inhibition in the outer retina, the horizontal cells. In accordance with immunohistochemical findings, P2X4-R immunogold labelling was expressed on horizontal processes at the ultrastructural level. Additionally, P2X4-R-IR was closely associated with axon terminals in both the OFF and ON sub-laminae of the IPL. Both P2X4-R-IR and NTPDase1-IR were apparent on microglia in the WT retina. In the rd1 retina, P2X4-R and NTPDase1 mRNA expressions were up-regulated at all ages examined. At the critical phase of rod death, microglia expressing P2X4-R and NTPDase1 were present in the ONL of the rd1 retina. In contrast, P2X4/NTPDase1-positive microglia were absent from the ONL of the WT retina.
The P2X4-R may be involved in modulating synaptic function and also microglial immuno-surveillance in the healthy retina. However, in RD, both P2X4-R and NTPDase1 expression is up-regulated and associated with activated microglia in the outer retina. These results suggest a role for the purinergic system in the mechanisms associated with photoreceptor death.
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