title: Role of ocular complement factor H in a murine model of choroidal neovascularization.
abstract: The objective of this study was to explore the relationship between local (ie, ocular) complement factor H (CFH) and choroidal neovascularization (CNV) associated with wet age-related macular degeneration (AMD), a leading cause of irreversible blindness, in laser-treated C57BL/6 mice. Immunohistochemical and RT-PCR analysis of retinal pigmented epithelium (RPE)-choroid sclera revealed that the expression of CFH was down-regulated on day 1 with a dramatic increase on days 5 and 7 postlaser injury. Flat mount and Western blot analysis further revealed that membrane attack complex (MAC) expression was up-regulated on days 1 and 3 postlaser injury; however, MAC was down-regulated on days 5 and 7 postinjury but was still higher than in non-injured mice. Similar patterns for CFH and MAC were observed for RPE cells when serial paraffin sections of the laser spots were analyzed. Subretinal injection of siRNA directed against CFH resulted in a threefold suppression of CFH in the RPE and choroid without affecting either CFH levels in the liver or the functional activity of the alternative pathway in the peripheral blood. Ocular knock-down of CFH resulted in increased MAC deposition, which leads to the early onset as well as exacerbation of laser-induced CNV. In conclusion, our findings provide evidence that CFH present on RPE and choroid regulates local MAC formation that is critical for the development of laser-induced CNV.
authors.affiliation: Department of Ophthalmology, Jones Eye Institute, Pat & Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: Valeriy V
authors.initials: VV
authors.lastname: Lyzogubov
authors.forename: Ruslana G
authors.initials: RG
authors.lastname: Tytarenko
authors.forename: Purushottam
authors.initials: P
authors.lastname: Jha
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Nalini S
authors.initials: NS
authors.lastname: Bora
authors.forename: Puran S
authors.initials: PS
authors.lastname: Bora
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020256:Choroidal Neovascularization / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D017242:Complement Factor H / Q000037:antagonists & inhibitors / Q000502:physiology*; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D007834:Lasers / Q000009:adverse effects*; D008268:Macular Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014785:Vision, Ocular / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017242:Complement Factor H
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