Purpose:
The dry form of macular degeneration in humans is believed to arise as a consequence of retinal pigment epithelium (RPE) apoptosis and photoreceptor atrophy 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 acts as a viral sensor by binding dsRNA and initiating a biological cascade leading to apoptosis. A TLR3 polymorphism is reportedly associated with geographic atrophy (GA). Our goal is to develop an experimental model of GA in rats using Poly I: C to activate TLR3, leading to RPE apoptosis and retinal degeneration
Methods:
A dose range of Poly I: C was administrated either intravenously and/or intravitreally in Brown Norway rats. Ocular changes were evaluated once a week for total 5 weeks post-Poly I: C administration by slit lamp, fundus photography and/or fluorescein angiography, autoflurescein, optical coherence tomography (OCT), and electroretinogram (ERG). Ocular histopathology (H&E staining) was also carried out at designated time points.
Results:
A single intravenous or intravitreal administration of Poly i: C causes retinal degeneration involving retinal pigmental cell loss within 7 days and outer retinal atrophy by 2 weeks. The size of retinal degeneration expanded from optic disc toward periphery of the retina in a time-dependent fashion. The fundus changes are similar to that seen in humans with GA. The incidence of this retinal degeneration in rat eyes increased in a dose-dependent fashion.
Conclusions:
TLR3 plays a vital role in the cell degeneration by detecting dsRNA derived from viruses or the death of cells. RPE cells express TLR3 receptors and thus may serve as the first line of defense in the retina. Our results indicate that activation of TLR3 with Poly I: C causes RPE apoptosis in the rat thus providing a valuable model of retinal degeneration and a tool to evaluate effective means of pharmacological intervention.
Keywords: retinal degenerations: cell biology • apoptosis/cell death • retinal pigment epithelium