title: Activated Müller Cells Involved in ATP-Induced Upregulation of P2X7Receptor Expression and Retinal Ganglion Cell Death.
abstract: P2X7receptor (P2X7R), an ATP-gated ion channel, plays an important role in glaucomatous retinal ganglion cell (RGC) apoptotic death, in which activated retinal Müller glial cells may be involved by releasing ATP. In the present study, we investigated whether and how activated Müller cells may induce changes in P2X7R expression in RGCs by using immunohistochemistry and Western blot techniques. Intravitreal injection of DHPG, a group I metabotropic glutamate receptor (mGluR I) agonist, induced upregulation of GFAP expression, suggestive of Müller cell activation (gliosis), as we previously reported. Accompanying Müller cell activation, P2X7R protein expression was upregulated, especially in the cells of ganglion cell layer (GCL), which was reversed by coinjection of brilliant blue G (BBG), a P2X7R blocker. In addition, intravitreal injection of ATP also induced upregulation of P2X7R protein expression. Similar results were observed in cultured retinal neurons by ATP treatment. Moreover, both DHPG and ATP intravitreal injection induced a reduction in the number of fluorogold retrogradely labeled RGCs, and the DHPG effect was partially rescued by coinjection of BBG. All these results suggest that activated Müller cells may release ATP and, in turn, induce upregulation of P2X7R expression in the cells of GCL, thus contributing to RGC death.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Nan
authors.identifier: 0000-0003-4866-4263
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Guowei
authors.identifier: 0000-0001-6059-1947
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Huaijin
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Min
authors.identifier: 0000-0002-7135-7256
authors.initials: M
authors.lastname: Ji
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D063928:Ependymoglial Cells / Q000378:metabolism*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D058486:Receptors, Purinergic P2X7; D008734:Methoxyhydroxyphenylglycol; D000255:Adenosine Triphosphate; C010117:3,4-dihydroxyphenylglycol