Age-related macular degeneration and the other double helix. The Cogan Lecture

Abstract

The study and therapy of age-related macular degeneration (AMD), a leading cause of blindness worldwide, have taken great strides over the past decade. During the same time, a central role for RNA in many human diseases has been discovered. We have identified anti-angiogenic functions for synthetic double stranded RNAs (dsRNAs) in neovascular AMD and cytotoxic functions for endogenous dsRNAs in atrophic AMD. These findings provide new insights into the pathogenesis and therapy of both forms of AMD.

Figure 1.

Calculating CNV using area measurements may lead to artifactual differences, as determined by precise focal plane during imaging. CNV lesion size is most accurately measured using volumetrics whereby areas derived from a z-stack of focal plane images are summed from the most anterior to posterior plane of the lesion, as seen in the orthogonal section of an FITC-lectin stained choroid 7 days after laser injury (a). When CNV lesion size is calculated by using area-based methodology, there may be large artifactual differences due to the observer choice of focal plane from which the image slice is taken. Thus, depending on whether the operator chosen image slice is selected from the anterior (yellow line), middle (blue line), or posterior (red line) aspect of the lesion (b), there will be large variation in the final area measurement (c–e).

Figure 2.

Intravitreous Luc siRNA administration leads to loss of GFP signal due to retinal degeneration[b]. Transgenic eGFP mice were treated with four intravitreous 21-nt Luc siRNA injections (1 μg). Dramatic retinal cell death and substantially decreased GFP signal were observed with Luc siRNA-treated eyes (b) compared with the PBS controls (a), as seen on RPE/choroid flat mount preparations. Scale bar, 100 μm.