Y1 receptor of neuropeptide Y as a glial marker in proliferative vitreoretinopathy and diseased human retina

Abstract

The Y1 receptor of neuropeptide Y (NPY) has been demonstrated in glial cells of astrocytic lineage in vitro. We have studied the immunohistochemical expression of Y1 receptors in the glia of the diseased human retina, in tissue samples obtained after surgery for proliferative vitreoretinopathy. In this condition, glia and other cell types migrate and form epi- or subretinal membranes. Both diseased retinas (n = 8) and PVR membranes (n = 43) contained numerous Y1-immunoreactive cells. In the diseased retina, the Y1 antiserum labeled cells with the morphological radial pattern characteristic of Müller cells, whereas in the membranes, label appeared in a large population of elongate cells, measuring up to 250 microm. In both retina and membranes, double labeling demonstrated that the vast majority of Y1-immunoreactive cells were also labeled by a glial fibrillary acidic protein (GFAP) antibody, indicating their glial origin. Retinal regions devoid of GFAP immunoreactivity also lacked the Y1 label. None of these markers was detected in Müller cells of normal retina. Y1 immunoreactivity did not co-localize with smooth muscle actin immunoreactivity, a marker of myofibroblasts. Expression of Y1 receptors would characterize reactive and proliferating glial cells of the diseased retina and could perhaps be involved in the proliferation of injured glial cells causing regrowth of PVR membranes and the consequent secondary retinal detachments.

NPY in rat retina is present in neurons, in endothelial cells and also in microglial and Müller cells

“…These results demonstrate, for the first time that NPY is present not only in retinal neurons, but also in glial cells in the retina. Some studies strongly suggest that retinal macroglia and microglia may be associated with retinal dysfunctions such as vitreoretinopathy, diabetic retinopathy, retinitis pigmentosa and age-related macular degeneration (Gupta et al, 2003;McGillem and Dacheux, 1998;RunggerBrandle et al, 2000;Soler et al, 2002). Therefore, the presence of NPY in retinal microglia may suggest a putative role of this peptide on inflammatory states observed in those retinal dysfunctions and should be further investigated (Leal et al, 2005;Meleth et al, 2005;Zhou et al, 2005).…”

Involvement of Müller glial cells in epiretinal membrane formation

“…Other receptor agonists Müller cells in the retina and glial cells in epiretinal membranes of patients with PVR express the Y 1 receptor of neuropeptide Y [227]. Neuropeptide Y has both antiproliferative (at low concentrations) and proliferative (at higher concentrations) effects in cultured Müller cells [228].…”

Blockade of Endothelinergic Receptors Prevents Development of Proliferative Vitreoretinopathy in Mice

“…27 Mice were deeply anesthetized (chloral hydrate, 800 mg/kg) and fixed by intracardiac perfusion with 4% paraformaldehyde in 0.1 mol/L phosphate buffer, pH 7.3. Specimens were cryoprotected 28 and frozen in N 2 -cooled acetone.…”