Figure 12.

Systems pharmacological strategies prevent the development of light-induced photoreceptor degeneration. In appropriate mouse models of human retinopathies, antagonists of multiple Gs-coupled GPCRs prevented photoreceptor cell death (red bar, top left). Moreover, pharmacological activation of Gi-coupled GPCRs (black arrow, top middle) that suppress adenylate cyclase activity (red bar, middle) preserved retinal structure and function against an environmental insult (prolonged exposure to intense illumination). Direct inhibition of AC was also beneficial (red line). Additionally, Gq-coupled GPCRs can participate in photoreceptor degeneration, and inhibition of these GPCRs also proved effective in protecting photoreceptors from light-induced degeneration (red bar, top right). Reproduced with permission from Chen Y, Palczewska G, Mustafi D, et al. Systems pharmacology identifies drug targets for Stargardt disease-associated retinal degeneration. J Clin Invest. 2013;123:5119–5134. Copyright © 2013 American Society for Clinical Investigation.