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M. Stefanidakis, C. Bigelow, S. Hanks, S. Poor, B. Jaffee, S.-M. Liao; Poly I:C-Induced Ocular Inflammation in vivo. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6146.
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Age-related macular degeneration (AMD) is the most common cause of blindness in developed countries. Presently, there is no effective treatment for the most prevalent atrophic (dry) form of AMD. Toll-like receptors (TLRs) have been shown to play an essential role in innate and adaptive immune responses in the eye, and are involved in the recognition of specific microbial pathogens. TLR3 which is expressed in retinal pigment epithelial cells in the retina binds viral ds RNA, leading to the activation of an innate immune response and subsequent apoptosis. There is growing evidence in the literature showing that inflammation strongly contributes to the development of AMD. The purpose of this study is to develop a murine model of ocular inflammation.
To develop a murine model of ocular inflammation, we injected increasing i.v. doses of a synthetic dsRNA analog, poly I:C systemically into C57BL/6 mice. Plasma and ocular tissues were collected 24 h-post injection for cytokine/chemokine profile analysis. To measure inflammation, retina and RPE/choroid/sclera were fixed, and stained for infiltrating neutrophils and macrophages. Using optical coherence tomography (OCT), images of retinas were obtained and analysed from mice treated with poly I:C.
Systemic administration of poly I:C to activate TLR3 in C57BL/6 mice led to increased expression of several inflammatory and adhesion molecules, such as ICAM-1 both systemically and in ocular tissues 3 hours post-stimulation compared to controls. Upregulation of inflammatory molecules in C57BL/6 mice subjected to poly I:C treatment correlated nicely with increased number of infiltrating macrophages to the retina in vivo. Interestingly, mice subjected to a single intravenous dose of poly I:C showed several retinal morphological abnormalities detected by OCT.
These findings indicate that poly I:C induces efficient leukocyte recruitment to the retina and can be used as a valuable model to study retinal inflammation and degeneration in mice.
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