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Oncotarget Jun 2011Photoreceptor cell death is the terminal event in a variety of retinal disorders including age-related macular degeneration, retinitis pigmentosa, and retinal... (Review)
Review
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.
Topics: Animals; Apoptosis; Cell Death; Humans; Models, Biological; Necrosis; Photoreceptor Cells; Receptor-Interacting Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 21670490
DOI: 10.18632/oncotarget.286 -
Scientific Reports Feb 2017Retinitis pigmentosa (RP) encompasses a group of retinal diseases resulting in photoreceptor loss and blindness. We have previously shown in the rd10 mouse model of RP,...
Retinitis pigmentosa (RP) encompasses a group of retinal diseases resulting in photoreceptor loss and blindness. We have previously shown in the rd10 mouse model of RP, that rd10 microglia drive degeneration of viable neurons. Norgestrel, a progesterone analogue, primes viable neurons against potential microglial damage. In the current study we wished to investigate this neuroprotective effect further. We were particularly interested in the role of fractalkine-CX3CR1 signaling, previously shown to mediate photoreceptor-microglia crosstalk and promote survival in the rd10 retina. Norgestrel upregulates fractalkine-CX3CR1 signaling in the rd10 retina, coinciding with photoreceptor survival. We show that Norgestrel-treated photoreceptor-like cells, 661Ws, and C57 explants modulate rd10 microglial activity in co-culture, resulting in increased photoreceptor survival. Assessment of Norgestrel's neuroprotective effects when fractalkine was knocked-down in 661 W cells and release of fractalkine was reduced in rd10 explants confirms a crucial role for fractalkine-CX3CR1 signaling in Norgestrel-mediated neuroprotection. To further understand the role of fractalkine in neuroprotection, we assessed the release of 40 cytokines in fractalkine-treated rd10 microglia and explants. In both cases, treatment with fractalkine reduced a variety of pro-inflammatory cytokines. These findings further our understanding of Norgestrel's neuroprotective properties, capable of modulating harmful microglial activity indirectly through photoreceptors, leading to increased neuroprotection.
Topics: Animals; CX3C Chemokine Receptor 1; Cells, Cultured; Chemokine CX3CL1; Cytokines; Disease Models, Animal; Female; Male; Mice; Neuroprotection; Norgestrel; Photoreceptor Cells; Progesterone; Retina; Signal Transduction
PubMed: 28216676
DOI: 10.1038/srep43067 -
The International Journal of... 2017Studies on amphioxus, representing the most basal group of chordates, can give insights into the evolution of vertebrate traits. The present review of amphioxus research... (Review)
Review
Studies on amphioxus, representing the most basal group of chordates, can give insights into the evolution of vertebrate traits. The present review of amphioxus research is focused on the physiology of light-guided behavior as well as on the fine structure, molecular biology, and electrophysiology of the nervous system, with special attention being given to the photoreceptive organs. The amphioxus visual system is especially interesting because four types of receptors are involved in light detection - dorsal ocelli and Joseph cells (both rhabdomeric photoreceptors) and the frontal eye and lamellar body (both ciliary photoreceptors). Here, we consider how the available information on photoreceptive organs and light-guided behavior in amphioxus helps generate hypotheses about the history of these features during chordate and subsequently vertebrate evolution.
Topics: Animals; Circadian Rhythm; Evolution, Molecular; Lancelets; Opsins; Photoreceptor Cells; Photoreceptor Cells, Vertebrate; Vertebrates; Vision, Ocular
PubMed: 29319115
DOI: 10.1387/ijdb.170230zk -
Current Biology : CB Oct 2005Red light triggers asexual development and represses sexual development in the fungus Aspergillus nidulans. This response has been shown to require a phytochrome... (Review)
Review
Red light triggers asexual development and represses sexual development in the fungus Aspergillus nidulans. This response has been shown to require a phytochrome red/far-red light photoreceptor, FphA, which is cytoplasmic and binds a tetrapyrrole chromophore. FphA exhibits similarities to both plant and bacterial phytochromes.
Topics: Aspergillus nidulans; Light; Photobiology; Photoreceptor Cells; Phytochrome; Reproduction, Asexual; Sexual Maturation
PubMed: 16243020
DOI: 10.1016/j.cub.2005.10.001 -
ELife Oct 2019Animals detect light using opsin photopigments. Xenopsin, a recently classified subtype of opsin, challenges our views on opsin and photoreceptor evolution. Originally...
Animals detect light using opsin photopigments. Xenopsin, a recently classified subtype of opsin, challenges our views on opsin and photoreceptor evolution. Originally thought to belong to the Gαi-coupled ciliary opsins, xenopsins are now understood to have diverged from ciliary opsins in pre-bilaterian times, but little is known about the cells that deploy these proteins, or if they form a photopigment and drive phototransduction. We characterized xenopsin in a flatworm, and found it expressed in ciliary cells of eyes in the larva, and in extraocular cells around the brain in the adult. These extraocular cells house hundreds of cilia in an intra-cellular vacuole (phaosome). Functional assays in human cells show xenopsin drives phototransduction primarily by coupling to Gαi. These findings highlight similarities between xenopsin and c-opsin and reveal a novel type of opsin-expressing cell that, like jawed vertebrate rods, encloses the ciliary membrane within their own plasma membrane.
Topics: Animals; Brain; Cell Membrane; Evolution, Molecular; Eye; GTP-Binding Protein alpha Subunits; Humans; Larva; Light Signal Transduction; Opsins; Peptides; Photoreceptor Cells; Photoreceptor Cells, Invertebrate; Photoreceptor Cells, Vertebrate; Phylogeny; Platyhelminths; Retinal Rod Photoreceptor Cells; Sequence Alignment; Sequence Analysis, Protein; Xenopus Proteins
PubMed: 31635694
DOI: 10.7554/eLife.45465 -
Journal of the Royal Society, Interface Apr 2010The sensory basis of magnetoreception in animals still remains a mystery. One hypothesis of magnetoreception is that photochemical radical pair reactions can transduce...
The sensory basis of magnetoreception in animals still remains a mystery. One hypothesis of magnetoreception is that photochemical radical pair reactions can transduce magnetic information in specialized photoreceptor cells, possibly involving the photoreceptor molecule cryptochrome. This hypothesis triggered a considerable amount of research in the past decade. Here, we present an updated picture of the radical-pair photoreceptor hypothesis. In our review, we will focus on insights that can assist biologists in their search for the elusive magnetoreceptors.
Topics: Animals; Electromagnetic Fields; Humans; Magnetics; Models, Biological; Orientation; Perception; Photoreceptor Cells
PubMed: 20129953
DOI: 10.1098/rsif.2009.0456.focus -
Progress in Retinal and Eye Research Sep 2012The light responses of rod and cone photoreceptors in the vertebrate retina are quantitatively different, yet extremely stable and reproducible because of the... (Review)
Review
The light responses of rod and cone photoreceptors in the vertebrate retina are quantitatively different, yet extremely stable and reproducible because of the extraordinary regulation of the cascade of enzymatic reactions that link photon absorption and visual pigment excitation to the gating of cGMP-gated ion channels in the outer segment plasma membrane. While the molecular scheme of the phototransduction pathway is essentially the same in rods and cones, the enzymes and protein regulators that constitute the pathway are distinct. These enzymes and regulators can differ in the quantitative features of their functions or in concentration if their functions are similar or both can be true. The molecular identity and distinct function of the molecules of the transduction cascade in rods and cones are summarized. The functional significance of these molecular differences is examined with a mathematical model of the signal-transducing enzymatic cascade. Constrained by available electrophysiological, biochemical and biophysical data, the model simulates photocurrents that match well the electrical photoresponses measured in both rods and cones. Using simulation computed with the mathematical model, the time course of light-dependent changes in enzymatic activities and second messenger concentrations in non-mammalian rods and cones are compared side by side.
Topics: Adaptation, Ocular; Animals; Calcium; Guanylate Cyclase-Activating Proteins; Humans; Ion Channels; Models, Animal; Models, Biological; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod Cell Outer Segment; Signal Transduction
PubMed: 22658984
DOI: 10.1016/j.preteyeres.2012.05.002 -
Experimental Eye Research Jan 2017Oxidative stress plays a key role in age-related macular degeneration and hereditary retinal degenerations. Light damage in rodents has been used extensively to model...
Oxidative stress plays a key role in age-related macular degeneration and hereditary retinal degenerations. Light damage in rodents has been used extensively to model oxidative stress-induced photoreceptor degeneration, and photo-oxidative injury from blue light is particularly damaging to photoreceptors. The endogenous factors protecting photoreceptors from oxidative stress, including photo-oxidative stress, are continuing to be elucidated. In this study, we evaluated the effect of blue light exposure on photoreceptors and its relationship to Nrf2 using cultured murine photoreceptor (661W) cells. 661W cells were exposed to blue light at 2500 lux. Exposure to blue light for 6-24 h resulted in a significant increase in intracellular reactive oxygen species (ROS) and death of 661W cells in a time-dependent fashion. Blue light exposure resulted in activation of Nrf2, as indicated by an increase in nuclear translocation of Nrf2. This was associated with a significant induction of expression of Nrf2 as well as an array of Nrf2 target genes, including antioxidant genes, as indicated by quantitative reverse transcription PCR (qRT-PCR). In order to determine the functional role of Nrf2, siRNA-mediated knockdown studies were performed. Nrf2-knockdown in 661W cells resulted in significant exacerbation of blue light-induced reactive oxygen species levels as well as cell death. Taken together, these findings indicate that Nrf2 is an important endogenous protective factor against oxidative stress in photoreceptor cells. This suggests that drugs targeting Nrf2 could be considered as a neuroprotective strategy for photoreceptors in AMD and other retinal conditions.
Topics: Animals; Apoptosis; Blotting, Western; Cell Count; Cell Line; Gene Expression Regulation; Light; Mice; NF-E2-Related Factor 2; Neuroprotection; Oxidative Stress; Photoreceptor Cells; RNA; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Retinal Degeneration
PubMed: 27923559
DOI: 10.1016/j.exer.2016.12.001 -
Philosophical Transactions of the Royal... Mar 2011The underlying mechanisms of polarization sensitivity (PS) have long remained elusive. For rhabdomeric photoreceptors, questions remain over the high levels of PS... (Review)
Review
The underlying mechanisms of polarization sensitivity (PS) have long remained elusive. For rhabdomeric photoreceptors, questions remain over the high levels of PS measured experimentally. In ciliary photoreceptors, and specifically cones, little direct evidence supports any type of mechanism. In order to promote a greater interest in these fundamental aspects of polarization vision, we examined a varied collection of studies linking membrane biochemistry, protein-protein interactions, molecular ordering and membrane phase behaviour. While initially these studies may seem unrelated to polarization vision, a common narrative emerges. A surprising amount of evidence exists demonstrating the importance of protein-protein interactions in both rhabdomeric and ciliary photoreceptors, indicating the possible long-range ordering of the opsin protein for increased PS. Moreover, we extend this direction by considering how such protein paracrystalline organization arises in all cell types from controlled membrane phase behaviour and propose a universal pathway for PS to occur in both rhabdomeric and cone photoreceptors.
Topics: Animals; Cell Membrane; Light; Opsins; Photoreceptor Cells; Retinal Cone Photoreceptor Cells; Vision, Ocular
PubMed: 21282166
DOI: 10.1098/rstb.2010.0206 -
Communications Biology Jan 2022Human cone phototropism is a key mechanism underlying the Stiles-Crawford effect, a psychophysiological phenomenon according to which photoreceptor outer/inner segments...
Human cone phototropism is a key mechanism underlying the Stiles-Crawford effect, a psychophysiological phenomenon according to which photoreceptor outer/inner segments are aligned along with the direction of incoming light. However, such photomechanical movements of photoreceptors remain elusive in mammals. We first show here that primate cone photoreceptors have a planar polarity organized radially around the optical center of the eye. This planar polarity, based on the structure of the cilium and calyceal processes, is highly reminiscent of the planar polarity of the hair cells and their kinocilium and stereocilia. Secondly, we observe under super-high resolution expansion microscopy the cytoskeleton and Usher proteins architecture in the photoreceptors, which appears to establish a mechanical continuity between the outer and inner segments. Taken together, these results suggest a comprehensive cellular mechanism consistent with an active phototropism of cones toward the optical center of the eye, and thus with the Stiles-Crawford effect.
Topics: Animals; Biomechanical Phenomena; Cell Polarity; Cytoskeleton; Light; Macaca fascicularis; Reproducibility of Results; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells
PubMed: 35075261
DOI: 10.1038/s42003-021-02998-y