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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 -
EBioMedicine Jan 2021Inherited retinal diseases (IRDs) were first classified clinically by history, ophthalmoscopic appearance, type of visual field defects, and electroretinography (ERG).... (Review)
Review
Inherited retinal diseases (IRDs) were first classified clinically by history, ophthalmoscopic appearance, type of visual field defects, and electroretinography (ERG). ERGs isolating the two major photoreceptor types (rods and cones) showed some IRDs with greater cone than rod retinal dysfunction; others were the opposite. Within the cone-rod diseases, there can be phenotypic variability, which can be attributed to genetic heterogeneity and the variety of visual function mechanisms that are disrupted. Most cause symptoms from childhood or adolescence, although others can manifest later in life. Among the causative genes for cone-rod dystrophy (CORD) are those encoding molecules in phototransduction cascade activation and recovery processes, photoreceptor outer segment structure, the visual cycle and photoreceptor development. We review 11 genes known to cause cone-rod disease in the context of their roles in normal visual function and retinal structure. Knowledge of the pathobiology of these genetic diseases is beginning to pave paths to therapy.
Topics: Age of Onset; Alleles; Genetic Association Studies; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Genotype; Humans; Mutation; Phenotype; Retinal Diseases; Retinal Rod Photoreceptor Cells; Vision, Ocular; Visual Acuity
PubMed: 33421946
DOI: 10.1016/j.ebiom.2020.103200 -
Physiology (Bethesda, Md.) Jan 2024One of the biggest environmental alterations we have made to our species is the change in the exposure to light. During the day, we typically sit behind glass windows... (Review)
Review
One of the biggest environmental alterations we have made to our species is the change in the exposure to light. During the day, we typically sit behind glass windows illuminated by artificial light that is >400 times dimmer and has a very different spectrum than natural daylight. On the opposite end are the nights that are now lit up by several orders of magnitude. This review aims to provide food for thought as to why this matters for humans and other animals. Evidence from behavioral neuroscience, physiology, chronobiology, and molecular biology is increasingly converging on the conclusions that the biological nonvisual functions of light and photosensory molecules are highly complex. The initial work of von Frisch on extraocular photoreceptors in fish, the identification of rhodopsins as the molecular light receptors in animal eyes and eye-like structures and cryptochromes as light sensors in nonmammalian chronobiology, still allowed for the impression that light reception would be a relatively restricted, localized sense in most animals. However, light-sensitive processes and/or sensory proteins have now been localized to many different cell types and tissues. It might be necessary to consider nonlight-responding cells as the exception, rather than the rule.
Topics: Humans; Animals; Photoreceptor Cells, Invertebrate; Cryptochromes
PubMed: 37905983
DOI: 10.1152/physiol.00017.2023 -
Progress in Brain Research 2022Photometry is the metrology of light-optical radiation seen by the human eye due to its action on retinal photoreceptors. Its origins are closely tied to the...
Photometry is the metrology of light-optical radiation seen by the human eye due to its action on retinal photoreceptors. Its origins are closely tied to the International Commission on Illumination (CIE), which remains responsible for photometry standards and the language of light used in science and technology. When in 1931 it had become possible to model the response to light of the human eye based on reliable spectroradiometry data, the CIE published standard formulae for predicting the luminance of a stimulus. These and related colorimetry formulae are still in use, having been internationally agreed and adopted. Both fields continue to be the subject of active research and increasing accuracy. CIE S 026:2018 represents another milestone for the metrology of light (CIE, 2018a). It is the first standard where light is considered for its ability to evoke circadian and neurophysiological responses, and includes the spectral sensitivity of melanopsin-a retinal photopigment discovered, and shown to be contributing to and influencing responses from human intrinsically-photosensitive retinal ganglion cells (ipRGCs), only 20 years ago (Berson et al., 2002; Hattar et al., 2002; Provencio et al., 1998). These accessory visual functions also depend to some extent on inputs from the rods and three types of cones; until very recently, rods and cones (or "classical photoreceptors") were the only photoreceptors in visual models. If photometry standards are replaced with modern physiological data, consistent changes should be expected in the photometry of these accessory functions. This chapter outlines the current standards, their definitions and calculations, and how the main elements are related.
Topics: Circadian Rhythm; Humans; Photometry; Photoreceptor Cells, Vertebrate; Retina; Retinal Cone Photoreceptor Cells; Retinal Ganglion Cells; Rod Opsins
PubMed: 35940711
DOI: 10.1016/bs.pbr.2022.02.014 -
International Journal of Molecular... Sep 2020Optogenetic (photo-responsive) actuators engineered from photoreceptors are widely used in various applications to study cell biology and tissue physiology. In the... (Review)
Review
Optogenetic (photo-responsive) actuators engineered from photoreceptors are widely used in various applications to study cell biology and tissue physiology. In the toolkit of optogenetic actuators, the key building blocks are genetically encodable light-sensitive proteins. Currently, most optogenetic photosensory modules are engineered from naturally-occurring photoreceptor proteins from bacteria, fungi, and plants. There is a growing demand for novel photosensory domains with improved optical properties and light-induced responses to satisfy the needs of a wider variety of studies in biological sciences. In this review, we focus on progress towards engineering of non-opsin-based photosensory domains, and their representative applications in cell biology and physiology. We summarize current knowledge of engineering of light-sensitive proteins including light-oxygen-voltage-sensing domain (LOV), cryptochrome (CRY2), phytochrome (PhyB and BphP), and fluorescent protein (FP)-based photosensitive domains (Dronpa and PhoCl).
Topics: Bacteria; Cryptochromes; Fungi; Optogenetics; Photoreceptor Cells; Photosensitizing Agents; Phytochrome; Plants; Protein Engineering
PubMed: 32906617
DOI: 10.3390/ijms21186522 -
Pflugers Archiv : European Journal of... Sep 2021Rhodopsin is the light receptor in rod photoreceptor cells that initiates scotopic vision. Studies on the light receptor span well over a century, yet questions about... (Review)
Review
Rhodopsin is the light receptor in rod photoreceptor cells that initiates scotopic vision. Studies on the light receptor span well over a century, yet questions about the organization of rhodopsin within the photoreceptor cell membrane still persist and a consensus view on the topic is still elusive. Rhodopsin has been intensely studied for quite some time, and there is a wealth of information to draw from to formulate an organizational picture of the receptor in native membranes. Early experimental evidence in apparent support for a monomeric arrangement of rhodopsin in rod photoreceptor cell membranes is contrasted and reconciled with more recent visual evidence in support of a supramolecular organization of rhodopsin. What is known so far about the determinants of forming a supramolecular structure and possible functional roles for such an organization are also discussed. Many details are still missing on the structural and functional properties of the supramolecular organization of rhodopsin in rod photoreceptor cell membranes. The emerging picture presented here can serve as a springboard towards a more in-depth understanding of the topic.
Topics: Animals; Cell Membrane; Humans; Protein Multimerization; Protein Structure, Secondary; Retinal Rod Photoreceptor Cells; Rhodopsin
PubMed: 33591421
DOI: 10.1007/s00424-021-02522-5 -
Experimental Eye Research Jan 2021Neuroretinal diseases are the predominant cause of irreversible blindness worldwide, mainly due to photoreceptor loss. Currently, there are no radical treatments to... (Review)
Review
Neuroretinal diseases are the predominant cause of irreversible blindness worldwide, mainly due to photoreceptor loss. Currently, there are no radical treatments to fully reverse the degeneration or even stop the disease progression. Thus, it is urgent to develop new biological therapeutics for these diseases on the clinical side. Stem cell-based treatments have become a promising therapeutic for neuroretinal diseases through the replacement of damaged cells with photoreceptors and some allied cells. To date, considerable efforts have been made to regenerate the diseased retina based on stem cell technology. In this review, we overview the current status of stem cell-based treatments for photoreceptor regeneration, including the major cell sources derived from different stem cells in pre-clinical or clinical trial stages. Additionally, we discuss herein the major challenges ahead for and potential new strategy toward photoreceptor regeneration.
Topics: Animals; Humans; Photoreceptor Cells; Regeneration; Retina; Retinal Degeneration; Stem Cell Transplantation; Visually Impaired Persons
PubMed: 33010290
DOI: 10.1016/j.exer.2020.108283 -
The Journal of Physiology Nov 2022The detection of light in the vertebrate retina utilizes a duplex system of closely related rod and cone photoreceptors: cones respond extremely rapidly, and operate at... (Review)
Review
The detection of light in the vertebrate retina utilizes a duplex system of closely related rod and cone photoreceptors: cones respond extremely rapidly, and operate at 'photopic' levels of illumination, from moonlight upwards; rods respond much more slowly, thereby obtaining greater sensitivity, and function effectively only at 'scotopic' levels of moonlight and lower. Rods and cones employ distinct isoforms of many of the proteins in the phototransduction cascade, and they thereby represent a unique evolutionary system, whereby the same process (the detection of light) uses a distinct set of genes in two classes of cell. The molecular mechanisms of phototransduction activation are described, and the classical quantitative predictions for the onset phase of the electrical response to light are developed. Recent work predicting the recovery phase of the rod's response to intense flashes is then presented, that provides an accurate account of the time that the response spends in saturation. Importantly, this also provides a new estimate for the rate at which a single rhodopsin activates molecules of the G-protein, transducin, that is substantially higher than other estimates in the literature. Finally, the evolutionary origin of the phototransduction proteins in rods and cones is examined, and it is shown that most of the rod/cone differences were established at the first of the two rounds of whole-genome duplication more than 500 million years ago.
Topics: Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Transducin; Retina; Light Signal Transduction
PubMed: 35412676
DOI: 10.1113/JP282058 -
Cells Dec 2021Lysosomes are membrane-bound cell organelles that respond to nutrient changes and are implicated in cell homeostasis and clearance mechanisms, allowing effective... (Review)
Review
Lysosomes are membrane-bound cell organelles that respond to nutrient changes and are implicated in cell homeostasis and clearance mechanisms, allowing effective adaptation to specific cellular needs. The relevance of the lysosome has been elucidated in a number of different contexts. Of these, the retina represents an interesting scenario to appreciate the various functions of this organelle in both physiological and pathological conditions. Growing evidence suggests a role for lysosome-related mechanisms in retinal degeneration. Abnormal lysosomal activation or inhibition has dramatic consequences on photoreceptor cell homeostasis and impacts extensive cellular function, which in turn affects vision. Based on these findings, a series of therapeutic methods targeting lysosomal processes could offer treatment for blindness conditions. Here, we review the recent findings on membrane trafficking, subcellular organization, mechanisms by which lysosome/autophagy pathway impairment affects photoreceptor cell homeostasis and the recent advances on developing efficient lysosomal-based therapies for retinal disorders.
Topics: Animals; Autophagy; Cell Survival; Homeostasis; Humans; Lysosomes; Photoreceptor Cells; Retinal Diseases
PubMed: 35011622
DOI: 10.3390/cells11010060 -
Journal of the Optical Society of... Jul 2021The intrinsic melanopsin photoresponse may initiate visual signals that differ in spatiotemporal characteristics from the cone-opsin- and rhodopsin-mediated signals....
The intrinsic melanopsin photoresponse may initiate visual signals that differ in spatiotemporal characteristics from the cone-opsin- and rhodopsin-mediated signals. Applying the CIE standard observer functions in silent-substitution methods can require individual differences in photoreceptor spectral sensitivities and pre-receptoral filtering to be corrected; failure to do so can lead to the intrusion of more sensitive cone processes with putative melanopsin-directed stimuli. Here we evaluate heterochromatic flicker photometry (HFP) and photoreceptor-directed temporal white noise as techniques to limit the effect of these individual differences. Individualized luminous efficiency functions (()) were compared to the CIE standard observer functions. We show that adapting chromaticities used in silent-substitution methods can deviate by up to 54% in luminance when estimated with the individual and standard observer functions. These deviations lead to inadvertent cone intrusions in the visual functions measured with melanopsin-directed stimuli. To eliminate the intrusions, individual HFP corrections are sufficient at low frequencies (∼1) but temporal white noise is also required at higher frequencies to desensitize penumbral cones. We therefore recommend the selective application of individualized observer calibration and/or temporal white noise in silent-substitution paradigms when studying melanopsin-directed photoresponses.
Topics: Cone Opsins; Humans; Photic Stimulation; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod Opsins
PubMed: 34263761
DOI: 10.1364/JOSAA.423343