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Drug Discovery Today Aug 2019The photoreceptors of the retina are afflicted by diseases that still often lack satisfactory treatment options. Although suitable drugs might be available in some... (Review)
Review
The photoreceptors of the retina are afflicted by diseases that still often lack satisfactory treatment options. Although suitable drugs might be available in some cases, the delivery of these compounds into the eye and across the blood-retinal barrier remains a significant challenge for therapy development. Here, we review the routes of drug administration to the retina and highlight different options for drug delivery to the photoreceptor cells.
Topics: Animals; Drug Delivery Systems; Humans; Pharmaceutical Preparations; Photoreceptor Cells, Vertebrate; Retina
PubMed: 30877076
DOI: 10.1016/j.drudis.2019.03.004 -
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 -
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 -
Cellular and Molecular Life Sciences :... Mar 2020Age-related macular degeneration (AMD) is a complex eye disease underlined by the death of photoreceptors and degeneration of retinal pigment epithelium (RPE) and... (Review)
Review
Age-related macular degeneration (AMD) is a complex eye disease underlined by the death of photoreceptors and degeneration of retinal pigment epithelium (RPE) and choriocapillaris (CC). The mechanism(s) responsible for massive and progressive retinal degeneration is not completely known. Senescence, a state of permanent inhibition of cell growth, may be induced by many factors important for AMD pathogenesis and results in senescence-associated secretory phenotype (SASP) that releases growth factors, cytokines, chemokines, proteases and other molecules inducing inflammation and other AMD-related effects. These effects can be induced in the affected cell and neighboring cells, leading to progression of AMD phenotype. Senescent cells also release reactive oxygen species that increase SASP propagation. Many other pathways of senescence-related AMD pathogenesis, including autophagy, the cGAS-STING signaling, degeneration of CC by membrane attack complex, can be considered. A2E, a fluorophore present in lipofuscin, amyloid-beta peptide and humanin, a mitochondria-derived peptide, may link AMD with senescence. Further studies on senescence in AMD pathogenesis to check the possibility of opening a perspective of the use of drugs killing senescent cells (senolytics) and terminating SASP bystander effects (senostatics) might be beneficial for AMD that at present is an incurable disease.
Topics: Cell Proliferation; Cellular Senescence; Choroid; Humans; Macular Degeneration; Photoreceptor Cells; Reactive Oxygen Species; Retinal Pigment Epithelium; Vision Disorders
PubMed: 31897543
DOI: 10.1007/s00018-019-03420-x -
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 Jun 2023Retinal detachment (RD) is a neurodegenerative blinding disease caused by plethora of clinical conditions. RD is characterized by the physical separation of retina from...
Retinal detachment (RD) is a neurodegenerative blinding disease caused by plethora of clinical conditions. RD is characterized by the physical separation of retina from the underlying retinal pigment epithelium (RPE), eventually leading to photoreceptor cell death, inflammation, and vision loss. Albeit the activation of complement plays a critical role in the pathogenesis of RD, the retinal cellular source for complement production remains elusive. Here, using C3 tdTomato reporter mice we show that retinal injury upregulates C3 expression, specifically in Müller cells. Activation of the complement cascade results in the generation of proinflammatory cleaved products, C3a and C5a, that bind C3aR and C5aR1, respectively. Our flow cytometry data show that retinal injury significantly upregulated C3aR and C5aR1 in microglia and resulted in the infiltration of peripheral immune cells. Loss of C3, C5, C3aR or C5aR1 reduced photoreceptor cell death and infiltration of microglia and peripheral immune cells into the sub-retinal space. These results indicate that C3/C3aR and C5/C5aR1 play a crucial role in eliciting photoreceptor degeneration and inflammatory responses in RD.
Topics: Mice; Animals; Ependymoglial Cells; Neuroinflammatory Diseases; Photoreceptor Cells; Cell Death; Retina; Retinal Detachment; Complement System Proteins
PubMed: 37443787
DOI: 10.3390/cells12131754 -
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