title: Steady-state levels of retinal 24S-hydroxycholesterol are maintained by glial cells intervention after elevation of intraocular pressure in the rat.
abstract: OBJECTIVE
  Our previous studies suggested that CYP46A1 and 24S-hydroxycholesterol (24SOH) may be associated with glaucoma. Loss of CYP46A1-expressing retinal ganglion cells is involved in the activation of glia, and therefore possibly in the disbalance of cholesterol. In this context, the purpose of our present work was to emphasize the glial and longitudinal CYP46A1 expression after an interventional glaucoma-related stress triggered by elevated intraocular pressure (IOP).
  
  
  METHODS
  Sprague-Dawley rats were submitted to laser photocoagulation of the trabecular meshwork, limbus and episcleral veins in one eye to induce elevated IOP. Rats were euthanized at days 3, 14, 30 and 60 (n = 10 per time-point), and 24SOH was measured in plasma and retina by gas chromatography-mass spectrometry. CYP46A1 was quantified by Western blotting. Glial activation was assessed by glial fibrillary acidic protein immunoreactivity in Western blots and retinal cryosections.
  
  
  RESULTS
  Sustained high IOP was observed in experimental eyes from day 1 to day 21. Plasma MCP-1 and ICAM-1, quantified using multiplex assay kits, were increased at day 3. Glial activation was observed bilaterally at all time-points, at lower levels in contralateral eyes than in experimental eyes. In experimental retinas, CYP46A1 expression showed a transient increase at day 3 and then returned to baseline. Plasma and retinal 24SOH peaked at day 14 and 30, respectively.
  
  
  CONCLUSIONS
  These data show that CYP46A1 expression was induced early in response to retinal stress but remained constant at late time-points, reinforcing the constitutive role of CYP46A1 in maintaining cholesterol balance in neuronal tissues.
authors.affiliation: INRA, UMR1324 CSGA, Eye and Nutrition Research Group, Dijon, France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fourgeux
authors.forename: Lucy
authors.initials: L
authors.lastname: Martine
authors.forename: Bruno
authors.initials: B
authors.lastname: Pasquis
authors.forename: Marie-Annick
authors.initials: MA
authors.lastname: Maire
authors.forename: Niyazi
authors.initials: N
authors.lastname: Acar
authors.forename: Catherine
authors.initials: C
authors.lastname: Creuzot-Garcher
authors.forename: Alain
authors.initials: A
authors.lastname: Bron
authors.forename: Lionel
authors.initials: L
authors.lastname: Bretillon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000072556:Cholesterol 24-Hydroxylase; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000097:blood* / Q000201:enzymology; D006706:Homeostasis; D006888:Hydroxycholesterols / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007429:Intraocular Pressure; D009457:Neuroglia / Q000378:metabolism*; D009798:Ocular Hypertension / Q000097:blood* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D006888:Hydroxycholesterols; D036341:Intercellular Signaling Peptides and Proteins; C044563:24-hydroxycholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase