University of Nebraska Medical Center

Molecular Targets for AMD

This figure shows laser-induced CNV lesions, their volume decreasing with the activation of Notch signaling.

Age-related macular degeneration (AMD) is the most common cause of progress vision loss in patients older than 60 in developed countries. The clinical hallmark of AMD is extracellular deposits called drusen, located between the retinal pigment epithelium (RPE) and the Bruch’s membrane. A subset of patients with drusen (dry AMD) progress to late AMD, also known as wet AMD, in which new vessels sprout from chorio-capillaries, which eventually invade the subretinal space, causing photoreceptor degeneration and rapid vision loss. This process is known as choroidal neovascularization (CNV). Wet AMD, in contrast to its dry counterpart, affects only 10% of AMD patients but accounts for most AMD-related vision loss. The underlying mechanism of wet AMD is not well understood, but evidence has emerged that pathologic recruitment of signaling pathways involved in normal angiogenesis, such as the VEGF pathway, play a critical role. Recent studies suggest that the VEGF pathway regulates angiogenesis in concert with Notch signaling. We are studying interactions of Notch signaling pathway with other angiogenic regulators in animal and retinal organoid models to identify therapeutic targets for AMD. Figure shows laser-induced CNV lesions, their volume decreasing with the activation of Notch signaling (Ahmad et al., 2011, IOVS).