title: Involvement of the CD200 receptor complex in microglia activation in experimental glaucoma.
abstract: The interaction of the myeloid restricted molecule CD200R with its widely expressed ligand CD200 is involved in the down-regulation of microglia activation. In the present study, we examined the involvement of CD200R in microglia activation in experimental ocular hypertension to determine the role of microglia activation in retinal ganglion cell (RGC) death, the key pathological event in glaucoma. Experimental glaucoma was induced in adult Brown Norway rats by sclerosis of the episcleral veins with the injection of hypertonic saline. Immunohistochemical methods were used to determine the involvement of microglia using GFAP, CD45, OX42 and OX41 and the involvement of CD200 and CD200R in the optic nerve head. Our data demonstrate the increased presence of microglia within the optic nerve head during ocular hypertension, identified by positive staining with OX42 and OX41. The peak of microglia correlates with peak in RGC death at days 20-27 (T3) post OHT induction. In addition, CD200 and CD200R positive cells were increased in ocular hypertensive eyes. Increased expression of CD200 was detected in the early phase (days 1-7; T1) of OHT and decreased over time, whilst the expression of CD200R was detected in the middle phase (days 20-27; T3) of OHT, correlating with the increase in microglia markers. Changes in the expression of CD200R/CD200 occur early in experimental glaucoma and precede the peak in microglia infiltration and RGC death, suggesting that CD200R-positive microglia play an important role in the initiation of RGC death during OHT, indicating a potential area for therapeutic intervention in treating glaucoma.
authors.affiliation: School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cathays Park, Cardiff CF24 4LU, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Taylor
authors.forename: Claudia J
authors.initials: CJ
authors.lastname: Calder
authors.forename: Julie
authors.initials: J
authors.lastname: Albon
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Erichsen
authors.forename: Micheal E
authors.initials: ME
authors.lastname: Boulton
authors.forename: James E
authors.initials: JE
authors.lastname: Morgan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D016923:Cell Death; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D005901:Glaucoma / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism*; D009898:Optic Disk / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011971:Receptors, Immunologic / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C495490:Cd200 protein, rat; D005904:Glial Fibrillary Acidic Protein; D011971:Receptors, Immunologic; D017493:Leukocyte Common Antigens