Recovery from apoptosis in photoreceptor cells: A role for mitophagy

Photoreceptors (PRs) are specialized light-sensitive cells responsible for vision, and their death is the primary cause of retinal degeneration and vision loss. Recent studies using cells such as HeLa and PC12 have demonstrated cellular recovery even from late stages of apoptosis. Here, we demonstrate for the first time that PR cells can recover from features of apoptosis following exposure to apoptotic stressors. Upon apoptotic stimuli (staurosporine or hypoxia), 661 W cells, a murine cone PR cell line, exhibited morphological and functional features of apoptosis, such as rounding and blebbing, caspase-3 activation, PARP cleavage, and phosphatidylserine externalization. These processes were reversed upon the alleviation of stress. We also observed that mitochondrial function is central to apoptotic recovery of photoreceptor cells, as evidenced by the restoration of intracellular ATP levels and reduction in mitochondrial reactive oxygen species (mROS). Mitophagy was demonstrated to play a crucial role in cell survival, with increased protein and mRNA expression of mitophagy markers during recovery from apoptosis. Furthermore, the modulation of mitophagy confirmed its protective role in the recovery phase, as its induction with MF-094 reduced apoptosis while its inhibition with Mdivi-1 exacerbated cell death. In vivo, we demonstrate the recovery of PRs from apoptosis using an experimental model of transient retinal detachment. Altogether, the findings of this study indicate that PR cells can recover from entry into the apoptotic cascade, and that mitophagy is essential for apoptotic recovery in these cells.