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M. Ni, K. Lalwani, G. Rodrigues, L. Wheeler; Animal Models of Dry Type Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):776.
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© ARVO (1962-2015); The Authors (2016-present)
Dry macular degeneration in humans is believed to arise as a consequence of retinal pigment epithelium (RPE) apoptosis and atrophy of retinal photoreceptors and choroid capillaries in the macula region of the eye, which results in irreversible vision loss. Polyinosine-polycytidylic acid (Poly I: C) is a synthetic double-stranded RNA (dsRNA) and toll-like receptor 3 (TLR3) agonist. TLR3 is a pattern-recognition receptor present in RPE cells that binds double-stranded viral RNA leading to activation of an innate immune response and apoptosis. Recent studies showed that a one-time intravenous (IV) injection of Poly I: C (2 µg) induced Geographic Atrophy in mouse eyes by acting through TLR3. Our goal is to develop an experimental model of Geographic Atrophy (GA) by systemic administration of Poly I: C to activate TLR3, leading to RPE apoptosis and the development of GA in rabbit, rat and mouse.
A dose range of Poly I: C was administrated intravenously in Dutch-Belted rabbits, Brown Norway rats or C57BL/6J mice. Ocular changes were evaluated on day 1, 3, 7, 14 and 28 post-Poly I: C administration by slit lamp, fundus photography and/or fluorescein angiography, optical coherence tomography (OCT), and electroretinogram (ERG). Ocular histopathology (H&E staining) was also carried out at designated time points.
Tested animal species included rabbits, rats, and mice receiving Poly I: C had fundal changes similar to that of humans with dry ARMD exhibiting soft and/or hard Drusen, geographic atrophy, and retinal detachment. The incidence of this dry ARMD-type retinal degeneration in rabbit, rat, and mouse eyes increased in a dose-dependent fashion.
TLR3 plays a vital role in the innate immune response by detecting viruses. RPE cells express TLR3 receptors and thus may serve as the first line of defense against invading organisms in the retina. Our results indicate that activation of TLR3 with Poly I: C causes RPE apoptosis in all three tested species, thus providing valuable models of macular degeneration and a tool for studies of the mechanisms of retinal degeneration and the discovery of new ophthalmic drugs.
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