title: Involvement of P2X7receptors in retinal ganglion cell apoptosis induced by activated Müller cells.
abstract: Müller cell reactivation (gliosis) is an early response in glaucomatous retina. Previous studies have demonstrated that activation of P2X7receptors results in retinal ganglion cell (RGC) apoptosis. Here, the issues of whether and how activated Müller cells may contribute to RGC apoptosis through P2X7receptors were investigated. Either intravitreal injection of (S)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR I) agonist, in normal rat retinas, or DHPG treatment of purified cultured rat retinal Müller cells induced an increase in glial fibrillary acidic protein (GFAP) expression, indicative of Müller cell gliosis. In addition, an increase in adenosine triphosphate (ATP) release from purified cultured Müller cells was detected during DHPG treatment (for 10 min to 48 h), which was mediated by the intracellular mGluR5/Gq/PI-PLC/PKC signaling pathway. Intravitreal injection of DHPG mimicked the reduction in the number of fluorogold retrogradely labeled RGCs in chronic ocular hypertension (COH) rats. Treatment with the conditioned culture medium (CM) obtained from the DHPG-activated Müller cell medium induced an increase in the number of TUNEL-positive cells in cultured RGCs, which was mimicked by benzoylbenzoyl adenosine triphosphate (BzATP), a P2X7receptor agonist, but was partially blocked by brilliant blue G (BBG), a P2X7receptor antagonist. Moreover, the CM treatment of cultured RGCs significantly increased Bax protein level and decreased Bcl-2 protein level, which was also mimicked by BzATP and partially blocked by BBG, respectively. These results suggest that reactivated Müller cells may release excessive ATP, in turn leading to RGC apoptosis through activating P2X7receptors in these cells.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China. Electronic address: guanhjeye@126.com.
authors.forename: Huaijin
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China. Electronic address: amyji1234@hotmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005901:Glaucoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000235:genetics* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D058486:Receptors, Purinergic P2X7; D004247:DNA
keywords: Apoptosis; Glaucoma; Müller cell gliosis; P2X(7) receptor; Retinal ganglion cell