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The Journal of General Physiology Mar 2018Vertebrate rod photoreceptors evolved the astonishing ability to respond reliably to single photons. In parallel, the proximate neurons of the visual system evolved the... (Review)
Review
Vertebrate rod photoreceptors evolved the astonishing ability to respond reliably to single photons. In parallel, the proximate neurons of the visual system evolved the ability to reliably encode information from a few single-photon responses (SPRs) as arising from the presence of an object of interest in the visual environment. These amazing capabilities were first inferred from measurements of human visual threshold by Hecht et al. (1942), whose paper has since been cited over 1,000 times. Subsequent research, in part inspired by Hecht et al.'s discovery, has directly measured rod SPRs, characterized the molecular mechanism responsible for their generation, and uncovered much about the specializations in the retina that enable the reliable transmission of SPRs in the teeth of intrinsic neuronal noise.
Topics: Animals; Humans; Photons; Retinal Rod Photoreceptor Cells; Sensory Thresholds; Vision, Ocular
PubMed: 29467164
DOI: 10.1085/jgp.201711970 -
Proceedings of the National Academy of... May 2017Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to...
Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of () rod cell clearance, () MG/progenitor cell proliferation, and () rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions.
Topics: Animals; Ependymoglial Cells; Humans; Immunity, Innate; Immunomodulation; Regeneration; Retinal Rod Photoreceptor Cells; Zebrafish
PubMed: 28416692
DOI: 10.1073/pnas.1617721114 -
Pflugers Archiv : European Journal of... Sep 2021All vertebrates share a canonical retina with light-sensitive photoreceptors in the outer retina. These photoreceptors are of two kinds: rods and cones, adapted to low... (Review)
Review
All vertebrates share a canonical retina with light-sensitive photoreceptors in the outer retina. These photoreceptors are of two kinds: rods and cones, adapted to low and bright light conditions, respectively. They both show a peculiar morphology, with long outer segments, comprised of ordered stacks of disc-shaped membranes. These discs host numerous proteins, many of which contribute to the visual transduction cascade. This pathway converts the light stimulus into a biological signal, ultimately modulating synaptic transmission. Recently, the zebrafish (Danio rerio) has gained popularity for studying the function of vertebrate photoreceptors. In this review, we introduce this model system and its contribution to our understanding of photoreception with a focus on the cone visual transduction cascade.
Topics: Animals; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Synapses; Vision, Ocular; Zebrafish
PubMed: 33598728
DOI: 10.1007/s00424-021-02528-z -
Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system.Molecular Vision Feb 2010The production of reactive oxygen species (ROS) can lead to oxidative stress, which is a strong contributory factor to many ocular diseases. In this study, the removal...
PURPOSE
The production of reactive oxygen species (ROS) can lead to oxidative stress, which is a strong contributory factor to many ocular diseases. In this study, the removal of trophic factors is used as a model system to investigate the effects of stress in the retina. The aims were to determine if both rod and cone photoreceptor cells produce ROS when they are deprived of trophic factor support and to demonstrate if the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes are responsible for this ROS production.
METHODS
Retinas were explanted from mice aged between postnatal days 8-10 and cultured overnight. The following morning, confocal microscopy combined with various fluorescent probes was used to detect the production of ROS. Each time peanut agglutinin (PNA), a cone photoreceptor marker, was used to facilitate orientation of the retina. Dihydroethidium and dihydrorhodamine 123 (DHR123) were used to determine which cells produce ROS. Subsequently, western blots of retinal serial sections were used to detect the presence of Noxs in the different retinal layers. The Nox inhibitor apocynin was then tested to determine if it altered the production of ROS within these cells.
RESULTS
Live retinal explants, viewed at high magnifications using confocal microscopy, displayed an increase in the fluorescent products of dihydroethidium and DHR123 upon serum removal when compared to controls. DHR123 fluorescence, once oxidized, localized to mitochondria and was found in the same focal plane as the PNA staining. This showed that cones and rods produced ROS when stressed. Retinal serial sectioning established that the photoreceptor layer expressed Nox4, dual oxidase (Duox) 1, and Duox2 at varying levels. Finally, the Nox inhibitor apocynin decreased the burst stimulated by the stress of serum removal.
CONCLUSIONS
Confocal microscopy and PNA staining allowed differentiation of cell types within the outermost layers of the retina, demonstrating that both rods and cones generated ROS in response to the stress of serum deprivation. Nox4 was the most abundantly expressed Nox in the photoreceptor layer, but Duox1 and Duox2 were also present at detectable levels, and as apocynin reduced the levels of ROS produced, this implied that these proteins may play some role in this production.
Topics: Acetophenones; Animals; Cell Differentiation; Mice; Mice, Inbred C57BL; Microscopy, Confocal; NADPH Oxidases; Peanut Agglutinin; Reactive Oxygen Species; Respiratory Burst; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Stress, Physiological; Tissue Culture Techniques
PubMed: 20177432
DOI: No ID Found -
Microscopy Research and Technique Sep 2000The photoreceptor population in Xenopus consists of a green-sensitive rod (lambda(max) = 523 nm), a blue-sensitive rod (lambda(max) = 445 nm) and three classes of cone.... (Review)
Review
The photoreceptor population in Xenopus consists of a green-sensitive rod (lambda(max) = 523 nm), a blue-sensitive rod (lambda(max) = 445 nm) and three classes of cone. The largest cone is red-sensitive (lambda(max) = 611 nm). The intermediate cone is presumed to be blue-sensitive based on physiological criteria, whereas the miniature cone may be UV-sensitive. Horizontal cells (HC) are of two sorts: axon-bearing and axonless. The axon-bearing HC is of the luminosity type and probably contacts all types of photoreceptor. The axonless HC is of the chromaticity type and contacts only intermediate (blue) cones and at least one type of rod. During development dendrites of HCs and bipolar neurons penetrate photoreceptor bases. A progressive maturation of HC and bipolar synapses with rods and cones occurs between tadpoles stages 37/8 and 46. Neighboring rods and cones are joined by gap junctions. During this same period, the outer segments are laid down and photopigments synthesized. A linear relation was found between the quantum capturing ability of the rod and its absolute threshold. Mature rods of the Xenopus retina release glutamate in a calcium-dependent manner. Glutamate release was found to be a linear function of calcium influx through L-type calcium channels. Both types of HC possess ionotropic glutamate receptors of the AMPA subtype.
Topics: Animals; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Synapses; Vision, Ocular; Xenopus laevis
PubMed: 10941170
DOI: 10.1002/1097-0029(20000901)50:5<338::AID-JEMT3>3.0.CO;2-I -
The Journal of General Physiology Jan 1998
Review
Topics: Animals; Mathematics; Retinal Rod Photoreceptor Cells; Vision, Ocular
PubMed: 9417131
DOI: 10.1085/jgp.111.1.3 -
Neurochemistry International Sep 2010Retinal dystrophies involve extensive photoreceptor apoptosis. Neuroprotective effects of insulin-like growth factor (IGF)-1 have been demonstrated in various tissues,...
Retinal dystrophies involve extensive photoreceptor apoptosis. Neuroprotective effects of insulin-like growth factor (IGF)-1 have been demonstrated in various tissues, including the retina. The aim of this study was to investigate: (i) the action of IGF-1 upon selective photoreceptor death induced by okadaic acid (OA); and (ii) signaling pathways related to both OA-induced cell death and IGF-1 neuroprotective effect. Retinal explants were incubated with 5nM OA, a protein phosphatase type 1 and type 2A inhibitor, which induces cell death detected by the identification of pyknotic morphology of photoreceptors immunostained for rhodopsin. OA increased both the number of pyknotic Rho 4D2(+) profiles, and Ca(2+) influx, measured through the incorporation of (45)CaCl(2), in a dose- and time-dependent way, while treatment with 10ng/mL IGF-1 abrogated both effects. Treatment with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, modulated OA effects, indicating the involvement of PKC. Furthermore, either 10microM chelerythrine chloride, an inhibitor of PKC, or 10microM nifedipine, a L-voltage-sensitive Ca(2+) channel blocker, inhibited both Ca(2+) influx and cell death induced by OA. The data show that okadaic acid induces rod photoreceptor cell death in retinal tissue through activation of PKC and ensuing Ca(2+) influx through L-type Ca(2+) channels, which is counteracted by a neuroprotective effect of IGF-1.
Topics: Animals; Calcium Channels, L-Type; Cell Death; Enzyme Activation; Insulin-Like Growth Factor I; Okadaic Acid; Protein Kinase C; Rats; Retinal Rod Photoreceptor Cells
PubMed: 20466029
DOI: 10.1016/j.neuint.2010.04.021 -
Physiology (Bethesda, Md.) Feb 2010Photoreceptor cells maintain a roughly constant length by continuously generating new outer segments from their base while simultaneously releasing mature outer segments... (Review)
Review
Photoreceptor cells maintain a roughly constant length by continuously generating new outer segments from their base while simultaneously releasing mature outer segments engulfed by the retinal pigment epithelium (RPE). Thus postmitotic RPE cells phagocytose an immense amount of material over a lifetime, disposing of photoreceptor cell waste while retaining useful content. This review focuses on current knowledge of outer segment phagocytosis, discussing the steps involved along with their critical participants as well as how various perturbations in outer segment (OS) disposal can lead to retinopathies.
Topics: Animals; Humans; Phagocytes; Phagocytosis; Retinal Cone Photoreceptor Cells; Retinal Diseases; Retinal Pigment Epithelium; Retinal Rod Photoreceptor Cells; Signal Transduction
PubMed: 20134024
DOI: 10.1152/physiol.00038.2009 -
The Journal of General Physiology Jul 2007Rod and cone photoreceptor cells that are responsible for scotopic and photopic vision, respectively, exhibit photoresponses different from each other and contain...
Rod and cone photoreceptor cells that are responsible for scotopic and photopic vision, respectively, exhibit photoresponses different from each other and contain similar phototransduction proteins with distinctive molecular properties. To investigate the contribution of the different molecular properties of visual pigments to the responses of the photoreceptor cells, we have generated knock-in mice in which rod visual pigment (rhodopsin) was replaced with mouse green-sensitive cone visual pigment (mouse green). The mouse green was successfully transported to the rod outer segments, though the expression of mouse green in homozygous retina was approximately 11% of rhodopsin in wild-type retina. Single-cell recordings of wild-type and homozygous rods suggested that the flash sensitivity and the single-photon responses from mouse green were three to fourfold lower than those from rhodopsin after correction for the differences in cell volume and levels of several signal transduction proteins. Subsequent measurements using heterozygous rods expressing both mouse green and rhodopsin E122Q mutant, where these pigments in the same rod cells can be selectively irradiated due to their distinctive absorption maxima, clearly showed that the photoresponse of mouse green was threefold lower than that of rhodopsin. Noise analysis indicated that the rate of thermal activations of mouse green was 1.7 x 10(-7) s(-1), about 860-fold higher than that of rhodopsin. The increase in thermal activation of mouse green relative to that of rhodopsin results in only 4% reduction of rod photosensitivity for bright lights, but would instead be expected to severely affect the visual threshold under dim-light conditions. Therefore, the abilities of rhodopsin to generate a large single photon response and to retain high thermal stability in darkness are factors that have been necessary for the evolution of scotopic vision.
Topics: Animals; Electrophysiology; Gene Duplication; Gene Expression Regulation; Mice; RNA, Messenger; Retinal Cone Photoreceptor Cells; Retinal Pigments; Retinal Rod Photoreceptor Cells; Time Factors; Vision, Ocular
PubMed: 17591985
DOI: 10.1085/jgp.200609729 -
Nature Neuroscience Apr 2010Rod photoreceptors were recently shown to contact 'Off' cone bipolar cells, providing an alternative pathway for rod signal flow in the mammalian retina. By recording... (Comparative Study)
Comparative Study
Rod photoreceptors were recently shown to contact 'Off' cone bipolar cells, providing an alternative pathway for rod signal flow in the mammalian retina. By recording from pairs of rods and Off cone bipolar cells in the ground squirrel (Spermophilus tridecemlineatus), we measured the synaptic responses of mammalian rods unfiltered by the slow kinetics of the rod bipolar cell response. We show that vesicle fusion and turnover in mammalian rods is fast, and that this new pathway can mediate rapid signaling.
Topics: Animals; Excitatory Postsynaptic Potentials; Photic Stimulation; Retina; Retinal Rod Photoreceptor Cells; Sciuridae; Signal Transduction; Synapses; Time Factors; Visual Pathways
PubMed: 20190742
DOI: 10.1038/nn.2507