title: Retinal changes precede visual dysfunction in the complement factor H knockout mouse.
abstract: We previously reported that aged mice lacking complement factor H (CFH) exhibit visual defects and structural changes in the retina. However, it is not known whether this phenotype is age-related or is the consequence of disturbed development. To address this question we investigated the effect of Cfh gene deletion on the retinal phenotype of young and mid-age mice. Cfh(-/-) mouse eyes exhibited thickening of the retina and reduced nuclear density, but relatively normal scotopic and photopic electroretinograms. At 12 months there was evidence of subtle astroglial activation in the Cfh(-/-) eyes, and significant elevation of the complement regulator, decay-accelerating factor (DAF) in Müller cells. In the retinal pigment epithelium (RPE) of young control and Cfh(-/-) animals mitochondria and melanosomes were oriented basally and apically respectively, whereas the apical positioning of melanosomes was significantly perturbed in the mid-age Cfh(-/-) RPE. We conclude that deletion of Cfh in the mouse leads to defects in the retina that precede any marked loss of visual function, but which become progressively more marked as the animals age. These observations are consistent with a lifelong role for CFH in retinal homeostasis.
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom.
authors.forename: Jennifer A E
authors.initials: JA
authors.lastname: Williams
authors.forename: John
authors.initials: J
authors.lastname: Greenwood
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Moss
mesh_terms: D000375:Aging; D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism; D017242:Complement Factor H / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004596:Electroretinography; D005074:Evoked Potentials, Visual / Q000235:genetics / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020460:Melanosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D010775:Photic Stimulation; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000648:ultrastructure; D014792:Visual Acuity / Q000235:genetics / Q000502:physiology*; D014795:Visual Pathways / Q000503:physiopathology
chemical_list: D018958:CD55 Antigens; D005904:Glial Fibrillary Acidic Protein; D017242:Complement Factor H