gms | German Medical Science

Background: Microglial cells are the intrinsic immune cells of the retina. Involvement of microglial cells in the pathology of CNV became of increasing interest. One critical point is to investigate the occurrence and the role of various receptors that may influence the behaviour of microglial cells. One family of such receptors are purinergic receptors that respond to ATP and initiate various processes in the microglial cells. We here report on four important purinergic receptors P2X4, P2X7, P2Y2 and P2Y12 and their inhibitor PPADS in the mouse model of laser-induced CNV.

Methods: Mice were treated with a laser to induce CNV and divided into four groups. One group received no subsequent treatment, and eyes were isolated at 1, 4, 7 and 14 days after laser treatment. Mice of the second, third and fourth group received intravitreal injection of 2 µl PPADS or PBS immediately after laser treatment or eye drops of PPADS once per day after laser treatment until the third day, respectively. Mice received fluorescence angiography examination at 4 days after laser treatment, and eyes were isolated to prepare cryosections for immunohistochemistry.

Results: In the normal mouse retina, microglial cells show almost no immunoreactivity for the investigated purinergic receptors. After laser treatment, immunoreactivity for the purinergic receptors increases clearly, with the maximum 4 days after laser treatment. After treatment with PPADS, immunoreactivity for P2X4, P2X7 and P2Y2 is clearly decreased, and there were less microglial cells positive for the purinergic receptors compared to PBS injection group.

Conclusion: We conclude that microglial cells express purinergic receptors P2X4, P2X7, P2Y2 and P2Y12 in laser-induced CNV, especially at 4 days after laser treatment. PPADS inhibits the expression of P2X4 and P2X7. Topical or intravitreal application of PPADS reduces the reactivity of microglial cells as well as the leakage of fluorescence from CNV.