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Biology of the Cell Feb 2013Over the past decades, there has been growing recognition that light can provide a powerful stimulus for biological interrogation. Light-actuated tools allow... (Review)
Review
Over the past decades, there has been growing recognition that light can provide a powerful stimulus for biological interrogation. Light-actuated tools allow manipulation of molecular events with ultra-fine spatial and fast temporal resolution, as light can be rapidly delivered and focused with sub-micrometre precision within cells. While light-actuated chemicals such as photolabile 'caged' compounds have been in existence for decades, the use of genetically encoded natural photoreceptors for optical control of biological processes has recently emerged as a powerful new approach with several advantages over traditional methods. Here, we review recent advances using light to control basic cellular functions and discuss the engineering challenges that lie ahead for improving and expanding the ever-growing optogenetic toolkit.
Topics: Animals; Humans; Light; Optogenetics; Photoreceptor Cells
PubMed: 23157573
DOI: 10.1111/boc.201200056 -
Acta Neuropathologica Communications Jan 2021Accumulation of misfolded host proteins is central to neuropathogenesis of numerous human brain diseases including prion and prion-like diseases. Neurons of retina are...
Accumulation of misfolded host proteins is central to neuropathogenesis of numerous human brain diseases including prion and prion-like diseases. Neurons of retina are also affected by these diseases. Previously, our group and others found that prion-induced retinal damage to photoreceptor cells in mice and humans resembled pathology of human retinitis pigmentosa caused by mutations in retinal proteins. Here, using confocal, epifluorescent and electron microscopy we followed deposition of disease-associated prion protein (PrPSc) and its association with damage to critical retinal structures following intracerebral prion inoculation. The earliest time and place of retinal PrPSc deposition was 67 days post-inoculation (dpi) on the inner segment (IS) of cone photoreceptors. At 104 and 118 dpi, PrPSc was associated with the base of cilia and swollen cone inner segments, suggesting ciliopathy as a pathogenic mechanism. By 118 dpi, PrPSc was deposited in both rods and cones which showed rootlet damage in the IS, and photoreceptor cell death was indicated by thinning of the outer nuclear layer. In the outer plexiform layer (OPL) in uninfected mice, normal host PrP (PrPC) was mainly associated with cone bipolar cell processes, but in infected mice, at 118 dpi, PrPSc was detected on cone and rod bipolar cell dendrites extending into ribbon synapses. Loss of ribbon synapses in cone pedicles and rod spherules in the OPL was observed to precede destruction of most rods and cones over the next 2-3 weeks. However, bipolar cells and horizontal cells were less damaged, indicating high selectivity among neurons for injury by prions. PrPSc deposition in cone and rod inner segments and on the bipolar cell processes participating in ribbon synapses appear to be critical early events leading to damage and death of photoreceptors after prion infection. These mechanisms may also occur in human retinitis pigmentosa and prion-like diseases, such as AD.
Topics: Animals; Cell Death; Disease Progression; Mice; Microscopy, Confocal; Microscopy, Electron; Microscopy, Fluorescence; Photoreceptor Connecting Cilium; PrPSc Proteins; Retinal Bipolar Cells; Retinal Cone Photoreceptor Cells; Retinal Photoreceptor Cell Inner Segment; Retinal Photoreceptor Cell Outer Segment; Retinal Rod Photoreceptor Cells; Scrapie
PubMed: 33509294
DOI: 10.1186/s40478-021-01120-x -
Investigative Ophthalmology & Visual... Sep 2008In examining the prospect of producing functional photoreceptors by reprogramming the differentiation of RPE progeny cells, this study was conducted to investigate...
PURPOSE
In examining the prospect of producing functional photoreceptors by reprogramming the differentiation of RPE progeny cells, this study was conducted to investigate whether reprogrammed cells can develop highly specialized ultrastructural and physiological traits that characterize retinal photoreceptors.
METHODS
Cultured chick RPE cells were reprogrammed to differentiate along the photoreceptor pathway by ectopic expression of neuroD. Cellular ultrastructure was examined with electron microscopy. Cellular physiology was studied by monitoring cellular free calcium (Ca(2+)) levels in dark-adapted cells in response to light and in light-bleached cells in response to 9-cis-retinal.
RESULTS
Reprogrammed cells were found to localize red opsin protein appropriately to the apex. These cells developed inner segments rich in mitochondria, and while in culture, some formed rudimentary outer segments, analogous to those of developing photoreceptors in the retina. In response to light, reprogrammed cells reduced their Ca(2+) levels, as observed with developing retinal photoreceptors in culture. Further, on exposure to 9-cis-retinal, the light-bleached, reprogrammed cells increased their Ca(2+) levels, reminiscent of visual cycle recovery.
CONCLUSIONS
These results indicate the potential of reprogrammed cells to develop advanced ultrastructural and physiological traits of photoreceptors and point to reprogramming progeny cells of embryonic RPE as a possible alternative in producing developing photoreceptors.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Calcium; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Chickens; Darkness; Diterpenes; Female; In Situ Hybridization; Light; Nerve Tissue Proteins; Photoreceptor Cells; Pigment Epithelium of Eye; Retinaldehyde
PubMed: 18469196
DOI: 10.1167/iovs.07-1380 -
The Journal of General Physiology Apr 2006
Review
Topics: Animals; Dark Adaptation; Light; Mice; Photoreceptor Cells; Retina; Retinal Cone Photoreceptor Cells; Rod Cell Outer Segment; Vision, Ocular
PubMed: 16567463
DOI: 10.1085/jgp.200609528 -
Trends in Neurosciences Nov 1996Exposure of the eye to bright light bleaches a significant fraction of the photopigment in rods and cones and produces a prolonged decrease in the sensitivity of vision,... (Review)
Review
Exposure of the eye to bright light bleaches a significant fraction of the photopigment in rods and cones and produces a prolonged decrease in the sensitivity of vision, which recovers slowly as the photopigment is regenerated. This sensitivity decrease is larger than would be expected merely from the decrease in the concentration of the pigment. Recent experiments have shown that the decrease in sensitivity is produced largely by an excitation of the phototransduction cascade by bleached pigment; even in darkness, it produces an equivalent background similar to that produced by real steady background illumination. Thus, excitation produced by a form of rhodopsin thought previously to be inactive has a profound effect on the physiology of the photoreceptor. This raises the possibility that forms of other G protein-coupled receptors thought to be inactive might also play an important role in signal transduction and disease.
Topics: Adaptation, Physiological; Animals; GTP-Binding Proteins; Photic Stimulation; Photoreceptor Cells
PubMed: 8931277
DOI: 10.1016/S0166-2236(96)10056-4 -
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 -
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 -
The Journal of Veterinary Medical... Mar 2018Owl monkeys are the only one species possessing the nocturnal lifestyles among the simian monkeys. Their eyes and retinas have been interested associating with the...
Owl monkeys are the only one species possessing the nocturnal lifestyles among the simian monkeys. Their eyes and retinas have been interested associating with the nocturnal adaptation. We examined the cellular specificity and electroretinogram (ERG) reactivity in the retina of the owl monkeys by comparison with the squirrel monkeys, taxonomically close-species and expressing diurnal behavior. Owl monkeys did not have clear structure of the foveal pit by the funduscope, whereas the retinal wholemount specimens indicated a small-condensed spot of the ganglion cells. There were abundant numbers of the rod photoreceptor cells in owl monkeys than those of the squirrel monkeys. However, the owl monkeys' retina did not possess superiority for rod cell-reactivity in the scotopic ERG responses. Scanning electron microscopic observation revealed that the rod cells in owl monkeys' retina had very small-sized inner and outer segments as compared with squirrel monkeys. Owl monkeys showed typical nocturnal traits such as rod-cell dominance. However, the individual photoreceptor cells seemed to be functionally weak for visual capacity, caused from the morphological immaturity at the inner and outer segments.
Topics: Animals; Aotidae; Electroretinography; Female; Male; Microscopy, Electron, Scanning; Night Vision; Ophthalmoscopes; Photoreceptor Cells, Vertebrate; Retina; Retinal Rod Photoreceptor Cells; Saimiri
PubMed: 29375079
DOI: 10.1292/jvms.17-0418 -
Clinical & Experimental Optometry May 2010Recently discovered intrinsically photosensitive melanopsin retinal ganglion cells contribute to the maintenance of pupil diameter, recovery and post-illumination... (Review)
Review
Recently discovered intrinsically photosensitive melanopsin retinal ganglion cells contribute to the maintenance of pupil diameter, recovery and post-illumination components of the pupillary light reflex and provide the primary environmental light input to the suprachiasmatic nucleus for photoentrainment of the circadian rhythm. This review summarises recent progress in understanding intrinsically photosensitive ganglion cell histology and physiological properties in the context of their contribution to the pupillary and circadian functions and introduces a clinical framework for using the pupillary light reflex to evaluate inner retinal (intrinsically photosensitive melanopsin ganglion cell) and outer retinal (rod and cone photoreceptor) function in the detection of retinal eye disease.
Topics: Adaptation, Ocular; Animals; Circadian Rhythm; Humans; Photoreceptor Cells; Reflex, Pupillary; Retinal Diseases; Retinal Ganglion Cells; Rod Opsins
PubMed: 20557555
DOI: 10.1111/j.1444-0938.2010.00479.x -
Scientific Reports Feb 2016We developed new optic devices - singly-doped luminescence glasses and nanoparticle-coated lenses that convert UV light to visible light - for improvement of visual...
We developed new optic devices - singly-doped luminescence glasses and nanoparticle-coated lenses that convert UV light to visible light - for improvement of visual system functions. Tb(3+) or Eu(3+) singly-doped borate glasses or CdS-quantum dot (CdS-QD) coated lenses efficiently convert UV light to 542 nm or 613 nm wavelength narrow-band green or red light, or wide-spectrum white light, and thereby provide extra visible light to the eye. In zebrafish (wild-type larvae and adult control animals, retinal degeneration mutants, and light-induced photoreceptor cell degeneration models), the use of Tb(3+) or Eu(3+) doped luminescence glass or CdS-QD coated glass lenses provide additional visible light to the rod and cone photoreceptor cells, and thereby improve the visual system functions. The data provide proof-of-concept for the future development of optic devices for improvement of visual system functions in patients who suffer from photoreceptor cell degeneration or related retinal diseases.
Topics: Animals; Disease Models, Animal; Light; Nanoparticles; Optical Devices; Photoreceptor Cells; Retinal Degeneration; Ultraviolet Rays; Zebrafish
PubMed: 26860393
DOI: 10.1038/srep20821