Apoptosis has been shown to be a significant form of cell loss in many diseases. Detachment of photoreceptors from the retinal pigment epithelium, as seen in various retinal disorders, causes photoreceptor loss and subsequent vision decline. Although caspasedependent apoptotic pathways are activated after retinal detachment, caspase inhibition by the pan-caspase inhibitor Z-VAD fails to prevent photoreceptor death; thus, we investigated other pathways leading to cell loss. Here, we show that receptor interacting protein (RIP) kinase-mediated necrosis is a significant mode of photoreceptor cell loss in an experimental model of retinal detachment and when caspases are inhibited, RIP-mediated necrosis becomes the predominant form of death. RIP3 expression, a key activator of RIP1 kinase, increased more than 10-fold after retinal detachment. Morphological assessment of detached retinas treated with Z-VAD showed decreased apoptosis but significantly increased necrotic photoreceptor death. RIP1 kinase inhibitor necrostatin-1 or Rip3 deficiency substantially prevented those necrotic changes and reduced oxidative stress and mitochondrial release of apoptosis-inducing factor. Thus, RIP kinase-mediated programmed necrosis is a redundant mechanism of photoreceptor death in addition to apoptosis, and simultaneous inhibition of RIP kinases and caspases is essential for effective neuroprotection and may be a novel therapeutic strategy for treatment of retinal disorders.degenerations | necroptosis P hotoreceptor death and subsequent visual decline occurs when the photoreceptors are separated from the underlying retinal pigment epithelium. Physical separation of photoreceptors is seen in various retinal disorders, including age-related macular degeneration (1), diabetic retinopathy (2), as well as rhegmatogenous (i.e., caused by a break in the retina) retinal detachment (3, 4). Although surgery is carried out to reattach the retina, only two fifths of patients with rhegmatogenous retinal detachment involving the macula, a region essential for central vision, recover 20/40 or better vision because of photoreceptor death (4, 5). Thus, identification of the mechanisms that underlie photoreceptor death is critical to developing new treatment strategies for these diseases.Apoptosis and necrosis are two major cell death modalities (6). Apoptosis is a highly regulated process involving the caspase family of cysteine proteases. In contrast, necrosis has been considered a passive, unregulated form of cell death; however, recent evidence indicates that some necrosis can be induced by regulated signal transduction pathways such as those mediated by receptor interacting protein (RIP) kinases, especially in conditions in which caspases are inhibited or cannot be activated efficiently (7,8). Stimulation of the Fas and TNFR family of death domain receptors is known to mediate apoptosis in most cell types through the activation of the extrinsic caspase pathway. In addition, in certain cells deficient for caspase-8 or treated with the pan-caspa...
SD-OCT is a fast and reliable tool for the in vivo evaluation of laser-induced CNV, allowing quantification of lesion size and exudation parameters. Moreover, it provides morphologic information that correlates with histologic findings.
Macular oedema (ME) occurs in a wide variety of pathological conditions and accounts for different degrees of vision loss. Early detection of ME is therefore critical for diagnosis and therapeutic management. Optical coherence tomography (OCT) is a non-contact, diagnostic method that uses infrared light, which allows the analysis of the retinal structure by means of high-resolution tomographic cross sections. The identification, localisation, quantification and long-term follow-up of fluid collections are the most important capabilities of OCT. Since the introduction of OCT in clinical practice, it has become an invaluable diagnostic tool and different patterns of ME have been reported. The purpose of this manuscript is to review OCT profiles of ME according to the aetiology and describe what has been reported regarding intraretinal features in vivo.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.