Complement activation in retinal degeneration

Matt Rutar, Riccardo Natoli, Jan Provis, Krisztina Valter

Research output: A Conference proceeding or a Chapter in BookOther chapter contributionpeer-review

4 Citations (Scopus)

Abstract

Our aim is to investigate a common role of the complement system in the pathogenesis of retinal disease, by assessing the expression profile of complement component 3 (C3) in three mechanistically distinct models of retinal degeneration: light-damage, hyperoxia and the degenerative P23H-3 rodent strain. In the light damage model, young adult albino Sprague Dawley (SD) rats were exposed to 1,000 lx for a period of up to 24 h, where at specific time points during and after exposure, animals were euthanized and retinas extracted for analysis. In the hyperoxia model, adult C57 mice were subjected to 75% oxygen for up to 14 days, then euthanized and retinas dissected for analysis. In the genetic model, SD and P23H-3 animals were born and reared until postnatal day 50-130, then euthanized and retinas extracted. For all three models, C3 mRNA expression levels were determined by quantitative PCR (qPCR), while photoreceptor death was quantified using the TUNEL technique. Up-regulation of C3 expression was evident in retinal tissue from all experimental models assessed. C3 expression in light damage showed a marked upregulation after 24 h of exposure, which continued into the post-exposure period. Modest increases in C3 were evident during early hyperoxia, which progressed to a substantial upregulation after 14 days. C3 expression in P23H retinas was consistently higher than those of non-degenerative SD retinas. Upregulation of C3 in all models was associated with substantial increases photoreceptor apoptosis. While the degenerative stimuli in these models differ, the increased expression of C3 in conjunction with increasing photoreceptor death provides evidence for a common pathway in retinal degeneration involving the activation of complement.

Original languageEnglish
Title of host publicationRetinal Degenerative Diseases
EditorsMatthew LaVail, Robert Anderson, Christian Grimm, John Ash, Joe Hollyfield
Place of PublicationUnited States
PublisherSpringer
Pages31-36
Number of pages6
ISBN (Electronic)9781461406310
ISBN (Print)9781461406303
DOIs
Publication statusPublished - 2012
Externally publishedYes
EventXIV International Symposium on Retinal Degeneration (RD2010) - Mont-Tremblant, Quebec, Canada
Duration: 13 Jul 201017 Jul 2010

Publication series

NameAdvances in Experimental Medicine and Biology
Volume723
ISSN (Print)0065-2598

Conference

ConferenceXIV International Symposium on Retinal Degeneration (RD2010)
Abbreviated titleRD2010
CountryCanada
CityQuebec
Period13/07/1017/07/10

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