Abstract
Photoreceptor cell death is the terminal event in a variety of retinal disorders including age-related macular degeneration, retinitis pigmentosa, and retinal detachment. Apoptosis has been thought to be the major form of cell death in these diseases, however accumulating evidence suggests that another pathway, programmed necrosis is also important. Recent studies have shown that, when caspase pathways are blocked, receptor interacting protein (RIP) kinases promote necrosis and overcome apoptosis inhibition. Therefore, targeting of both caspase and RIP kinase pathways are required for effective photoreceptor protection. Here, we summarize the current knowledge of RIP kinase-mediated necrotic signaling and its contribution to photoreceptor death.
Highlights
Photoreceptor death is the ultimate cause of vision loss in many retinal disorders
Using experimental models of retinal detachment, we recently demonstrated via electron microscopy and molecular biology analysis that programmed necrosis is a significant mode of photoreceptor cell death after RD and that the receptor interacting protein (RIP) kinase pathway plays an important role in the induction of photoreceptor necrosis, especially when caspase pathways are inhibited [64]
We investigated the role of RIP kinase-mediated necrosis in experimental models of retinal detachment, and observed that RIP3 expression increases over 10-fold in the detached retina, especially in the outer nuclear layer
Summary
Photoreceptor death is the ultimate cause of vision loss in many retinal disorders. Photoreceptors die when they are physically separated from the underlying retinal pigment epithelium (RPE) and choroidal vessels, which provide metabolic support to the outer layers of the retina. The retina in patients with rhegmatogenous retinal detachment exhibits a similar pattern and time course of photoreceptor death observed in experimental retinal detachment [6] These studies suggest that photoreceptor death may be one of the causes of vision loss after retinal detachment. In dry AMD, geographic atrophy is a serious cause of vision loss It results from a slowly progressive atrophy of RPE and photoreceptors. This programmed form of necrosis is termed programmed necrosis or necroptosis [24,25]
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