Expression of complement component 3 (C3) from an adenovirus leads to pathology in the murine retina.

Abstract:

PURPOSE:Activation of complement has been implicated as one of the major causes of age-related macular degeneration (AMD). Evidence is accumulating for a role of complement in other retinal diseases, such as diabetic retinopathy and proliferative vitreoretinopathy. Because of the paucity of animal models that directly investigate the role of complement in retinal pathology, the authors sought to develop a model of increased complement expression and activation, specifically in the murine retina. METHODS:The authors constructed a recombinant adenovirus-expressing murine complement component 3 (C3, AdcmvC3). Adult mice were injected in the subretinal space with either AdcmvC3 or a control virus, AdcmvGFP. After 1 to 2 weeks of exogenous C3 expression, mice were analyzed by scotopic electroretinography and fluorescein angiography. Eyes were harvested for histologic, immunohistochemical, and quantitative RT-PCR analyses. RESULTS:Mice injected with C3-expressing adenovirus exhibited significantly increased vascular permeability, endothelial cell proliferation and migration, RPE atrophy, loss of photoreceptor outer segments, reactive gliosis, retinal detachment, and reduced retinal function relative to those injected with a control adenovirus. Deposition of the membrane attack complex was observed on endothelial cells and photoreceptor outer segments. CONCLUSIONS:Adenovirus-mediated delivery of C3 to murine RPE induces significant functional and anatomic changes that reproduce many of the features of AMD as well as those of other retinal diseases. This novel model may be useful in assessing the role of complement in retinal pathology and in developing anti-complement therapies for retinal diseases associated with complement activation.

authors

Cashman SM,Desai A,Ramo K,Kumar-Singh R

doi

10.1167/iovs.10-6002

subject

Has Abstract

pub_date

2011-05-18 00:00:00

pages

3436-45

issue

6

eissn

0146-0404

issn

1552-5783

pii

iovs.10-6002

journal_volume

52

pub_type

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