Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction.
Age-related macular degeneration is the most common form of legal blindness in westernized societies, and polymorphisms in the gene encoding complement factor H (CFH) are associated with susceptibility to age-related macular degeneration in more than half of affected individuals. To investigate the relationship between complement factor H (CFH) and retinal disease, we performed functional and anatomical analysis in 2-year-old CFH-deficient (cfh(-/-)) mice. cfh(-/-) animals exhibited significantly reduced visual acuity and rod response amplitudes on electroretinography compared with age-matched controls. Retinal imaging by confocal scanning laser ophthalmoscopy revealed an increase in autofluorescent subretinal deposits in the cfh(-/-) mice, whereas the fundus and vasculature appeared normal. Examination of tissue sections showed an accumulation of complement C3 in the neural retina of the cfh(-/-) mice, together with a decrease in electron-dense material, thinning of Bruch's membrane, changes in the cellular distribution of retinal pigment epithelial cell organelles, and disorganization of rod photoreceptor outer segments. Collectively, these data show that, in the absence of any specific exogenous challenge to the innate immune system, CFH is critically required for the long-term functional health of the retina.
Coffey
Peter J
PJ
Division of Cellular Therapy, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
Gias
Carlos
C
McDermott
Caroline J
CJ
Lundh
Peter
P
Pickering
Matthew C
MC
Sethi
Charanjit
C
Bird
Alan
A
Fitzke
Fred W
FW
Maass
Annelie
A
Chen
Li Li
LL
Holder
Graham E
GE
Luthert
Philip J
PJ
Salt
Thomas E
TE
Moss
Stephen E
SE
Greenwood
John
J
D000375:Aging; D000818:Animals; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism; D017242:Complement Factor H / Q000172:deficiency* / Q000235:genetics; D005453:Fluorescence; D007113:Immunity, Innate; D051379:Mice; D008817:Mice, Mutant Strains; D012160:Retina / Q000002:abnormalities* / Q000737:chemistry / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology; D014786:Vision Disorders / Q000235:genetics*
D003176:Complement C3; D017242:Complement Factor H