Proposed model of Fas-mediated death of photoreceptors under light stress

Proposed model of Fas-mediated death of photoreceptors under light stress. Intense and prolonged light causes damage of photoreceptors by photo-oxidative stress via generation of ROS. The toxic all-trans retinal (ATR) and retinal derivatives generated during photoisomerization of the chromophore 11-cis retinal also render photoreceptors vulnerable to death. Early damaged photoreceptors can have disorganized outer segments, followed by their reduction and loss. Eventual death of photoreceptors can be executed by apoptosis through the “intrinsic” pathway as shown. Necrosis as demonstrated in this study and activation of the scavenging pathway by autophagy also are involved. We also demonstrate that apoptosis in photoreceptors under light stress occurs through the “extrinsic” FasL/Fas pathway involving activation of downstream caspases. While inhibition of caspases or Fas can prevent apoptosis by light, it simultaneously induces secondary cell death by necroptosis.

Publication

Fas Ligand-Fas Signaling Participates in Light-Induced Apoptotic Death in Photoreceptor Cells. (2012) Qing Chang, et al. Invest Ophthalmol Vis Sci. 2012 Jun;53(7):3703-3716. Figure: F9. All organisms Mus musculus Homo sapiens

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