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Advances in Experimental Medicine and... 2017This review discusses recent advances towards understanding the sigma-1 receptor (S1R) as an endogenous neuro-protective mechanism in the retina , a favorable... (Review)
Review
This review discusses recent advances towards understanding the sigma-1 receptor (S1R) as an endogenous neuro-protective mechanism in the retina , a favorable experimental model system. The exquisite architecture of the mammalian retina features layered and intricately wired neurons supported by non-neuronal cells. Ganglion neurons, photoreceptors , as well as the retinal pigment epithelium, are susceptible to degeneration that leads to major retinal diseases such as glaucoma , diabetic retinopathy , and age-related macular degeneration (AMD), and ultimately, blindness. The S1R protein is found essentially in every retinal cell type, with high abundance in the ganglion cell layer. Ultrastructural studies of photoreceptors, bipolar cells, and ganglion cells show a predominant localization of S1R in the nuclear envelope. A protective role of S1R for ganglion and photoreceptor cells is supported by in vitro and in vivo experiments. Most recently, studies suggest that S1R may also protect retinal neurons via its activities in Müller glia and microglia. The S1R functions in the retina may be attributed to a reduction of excitotoxicity, oxidative stress , ER stress response, or inflammation. S1R knockout mice are being used to delineate the S1R-specific effects. In summary, while significant progress has been made towards the objective of establishing a S1R-targeted paradigm for retinal neuro-protection , critical questions remain. In particular, context-dependent effects and potential side effects of interventions targeting S1R need to be studied in more diverse and more clinically relevant animal models.
Topics: Animals; Neuroprotective Agents; Photoreceptor Cells; Receptors, sigma; Retina; Retinal Diseases; Retinal Ganglion Cells; Retinal Neurons; Sigma-1 Receptor
PubMed: 28315278
DOI: 10.1007/978-3-319-50174-1_19 -
Cellular Signalling Dec 2017Molecular chaperones play pivotal roles in protein folding, quality control, assembly of multimeric protein complexes, protein trafficking, stress responses, and other... (Review)
Review
Molecular chaperones play pivotal roles in protein folding, quality control, assembly of multimeric protein complexes, protein trafficking, stress responses, and other essential cellular processes. Retinal photoreceptor rod and cone cells have an unusually high demand for production, quality control, and trafficking of key phototransduction components, and thus, require a robust and specialized chaperone machinery to ensure the fidelity of sensing and transmission of visual signals. Misfolding and/or mistrafficking of photoreceptor proteins are known causes for debilitating blinding diseases. Phosphodiesterase 6, the effector enzyme of the phototransduction cascade, relies on a unique chaperone aryl hydrocarbon receptor (AhR)-interacting protein-like 1 (AIPL1) for its stability and function. The structure of AIPL1 and its relationship with the client remained obscure until recently. This review summarizes important recent advances in understanding the mechanisms underlying normal function of AIPL1 and the protein perturbations caused by pathogenic mutations.
Topics: Adaptor Proteins, Signal Transducing; Carrier Proteins; Cyclic Nucleotide Phosphodiesterases, Type 6; Eye Proteins; Humans; Light Signal Transduction; Molecular Chaperones; Multiprotein Complexes; Mutation; Photoreceptor Cells, Vertebrate; Protein Folding; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Signal Transduction
PubMed: 28939106
DOI: 10.1016/j.cellsig.2017.09.014 -
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 -
Biochemical and Biophysical Research... Oct 2018Calpains are Ca-dependent cysteine proteases that are widely distributed in animal tissues and modulate a variety of cellular processes. There are 15 members of the...
Calpains are Ca-dependent cysteine proteases that are widely distributed in animal tissues and modulate a variety of cellular processes. There are 15 members of the calpain family in mammals. In animal cells, there are three types of calpains, viz., calpain-1, calpain-2, and calpain-10 in the mitochondria. The three types of calpains have been shown to play significant roles in pathophysiological conditions, including in apoptosis- and necrosis-like cell death. One of the severe retinal diseases, autosomal dominant neovascular inflammatory vitreoretinopathy, is known to be induced by mutations of the calpain-5 gene. However, the distribution of calpain-5 in the retina has not been elucidated. Therefore, in the present study, we determined the localization of calpain-5 in the porcine retina. We detected calpain-5 in the inner segment of photoreceptor cells using immunohistochemistry. With immunoelectron microscopy, calpain-5 was localized in the mitochondria of photoreceptor cells. Western blot analyses showed that calpain-5 was present in each mitochondrial subfraction. Furthermore, we showed that the molecular weight of mitochondrial calpain-5 was slightly smaller than cytosolic one. Our results demonstrated that a novel mitochondrial calpian, calpain-5, was localized in the mitochondria of retinal photoreceptor cells.
Topics: Animals; Calpain; Cytosol; Electrons; Gene Expression Profiling; Gene Expression Regulation; Inflammation; Microscopy, Immunoelectron; Mitochondria; Photoreceptor Cells; Photoreceptor Cells, Vertebrate; Retina; Subcellular Fractions; Swine
PubMed: 30195492
DOI: 10.1016/j.bbrc.2018.08.144 -
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 -
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 -
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 -
Cellular and Molecular Life Sciences :... Oct 2017Visual perception by photoreceptors relies on the interaction of incident photons from light with a derivative of vitamin A that is covalently linked to an opsin... (Review)
Review
Visual perception by photoreceptors relies on the interaction of incident photons from light with a derivative of vitamin A that is covalently linked to an opsin molecule located in a special subcellular structure, the photoreceptor outer segment. The photochemical reaction produced by the photon is optimal when the opsin molecule, a seven-transmembrane protein, is embedded in a lipid bilayer of optimal fluidity. This is achieved in vertebrate photoreceptors by a high proportion of lipids made with polyunsaturated fatty acids, which have the detrimental property of being oxidized and damaged by light. Photoreceptors cannot divide, but regenerate their outer segments. This is an enormous energetic challenge that explains why photoreceptors metabolize glucose through aerobic glycolysis, as cancer cells do. Uptaken glucose produces metabolites to renew that outer segment as well as reducing power through the pentose phosphate pathway to protect photoreceptors against oxidative damage.
Topics: Animals; Fatty Acids; Glucose; Humans; Oxidation-Reduction; Oxidative Stress; Pentose Phosphate Pathway; Photoreceptor Cells; Retina; Retinal Diseases; Rhodopsin; Signal Transduction
PubMed: 27543457
DOI: 10.1007/s00018-016-2318-7