title: P2X₇ receptor activation may be involved in neuronal loss in the retinal ganglion cell layer after acute elevation of intraocular pressure in rats.
abstract: OBJECTIVE
  To investigate whether the P2X₇ receptor is involved in retinal ganglion cell (RGC) death after the intraocular pressure (IOP) is elevated in rats.
  
  
  METHODS
  After the IOP was elevated to 90 mmHg for 1 h, the rats were subsequently administered oxidized adenosine triphosphate (OxATP) and brilliant blue G (BBG) as P2X₇ antagonists. The rats were euthanized 7 days after IOP elevation for histologic evaluation and at 1, 3, and 7 days after IOP elevation to immunostain for the P2X₇ receptor and neuron-specific class III β-tubulin in the retina. Changes in P2X₇ receptor expression were measured in total retina extracts using western blot analysis. Quantitative real-time PCR was also performed using the entire retina to determine whether the P2X₇ receptor is involved in upregulating tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 at 1, 2, and 3 days after the IOP was elevated.
  
  
  RESULTS
  RGC density and the inner plexiform layer thickness significantly decreased 7 days after IOP elevation, but were dose-dependently preserved when treated with OxATP or BBG. P2X₇ immunoreactivity in the RGCs increased after IOP elevation, with the peak occurring from day 1 through day 3. Protein levels of P2X₇ receptor were significantly increased 1, 2, and 3 days after IOP elevation. The messenger ribonucleic acid expression of the P2X₇ receptor, TNF-α, IL-1β, and IL-6 was significantly upregulated in the retina after IOP elevation, and was suppressed by treatment with OxATP.
  
  
  CONCLUSIONS
  These results suggest the expression of the P2X₇ receptor is upregulated in the retina after IOP elevation, leading to RGC death. Upregulation of TNF-α, IL-1β, and IL-6 might be involved in this mechanism of RGC death. Furthermore, P2X₇ antagonists may prevent RGC death after IOP elevation.
authors.affiliation: Department of Ophthalmology, Osaka Medical College, Takatsuki, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sugiyama
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Taeko
authors.initials: T
authors.lastname: Horie
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Oku
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tanioka
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kuriki
authors.forename: Shota
authors.initials: S
authors.lastname: Kojima
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects / Q000235:genetics; D008297:Male; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D007378:Interleukins; D058920:Purinergic P2X Receptor Antagonists; D012333:RNA, Messenger; D058486:Receptors, Purinergic P2X7; D014409:Tumor Necrosis Factor-alpha