Photoreceptor cell death and rescue in retinal detachment and degenerations

Abstract

Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss.

Impact of Metamorphopsia on Quality of Life after Successful Retinal Detachment Surgery

“…Consequently, the cone loss secondary to RD may result not only in a visual acuity decrease [40], but also in distorted vision. Interestingly, the few patients with macula-on RD who developed metamorphopsia after surgery displayed a hyporeflective outer retina on SD-OCT imaging, suggesting a photoreceptor impairment by mechanisms other than the mechanical disruption of the outer segments such as the inflammation triggered by RD [32, 33, 41]. …”

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

“…Most defective, unwanted and potentially dangerous cells die by apoptosis, an exquisitely controlled genetic program for removing such cells without damaging the surrounding tissue (for a review, see (Murakami et al, 2013)). The life-or-death decision seems to be the result of a complex balance between pro-and anti-apoptotic signals ( Fig.…”

“…In this sense, nuclear translocation of AIF and EndoG in various retinal degenerations has already been shown to occur (Hisatomi et al, 2001;Leal et al, 2009;Mizukoshi et al, 2010;Munemasa et al, 2010;Sizova et al, 2014;Zanna et al, 2005). Alternative mechanisms of cell death such as autophagy are receiving increasing attention among the mechanisms involved in retinal degeneration (Chinskey et al, 2014;Kunchithapautham and Rohrer, 2007;Murakami et al, 2013). Complete disruption of lysosomes provokes uncontrolled cell death by necrosis, but partial and selective lysosomal membrane permeabilization induces the controlled dismantling of the cell by apoptosis.…”

Identification of functional networks associated with cell death in the retina of OXYS rats during the development of retinopathy

“…4 Functional studies in animal and cellular models have greatly expanded the understanding of the function of apoptosis in eye development and homeostasis, 5 but the molecular genetic background and the mode of death of photoreceptors in AMD are still unclear. 6 Cell death in the retina is controlled by complex mechanisms, which are poorly understood at present; this state of affairs hinders the development of effective treatments of AMD.…”