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The Journal of Membrane Biology Oct 2019Rhodopsin is the light receptor in photoreceptor cells of the retina and a prototypical G protein-coupled receptor. Two types of quaternary structures can be adopted by... (Review)
Review
Rhodopsin is the light receptor in photoreceptor cells of the retina and a prototypical G protein-coupled receptor. Two types of quaternary structures can be adopted by rhodopsin. If rhodopsin folds and attains a proper tertiary structure, it can then form oligomers and nanodomains within the photoreceptor cell membrane. In contrast, if rhodopsin misfolds, it cannot progress through the biosynthetic pathway and instead will form aggregates that can cause retinal degenerative disease. In this review, emerging views are highlighted on the supramolecular organization of rhodopsin within the membrane of photoreceptor cells and the aggregation of rhodopsin that can lead to retinal degeneration.
Topics: Animals; Cell Membrane; Humans; Photoreceptor Cells, Vertebrate; Protein Domains; Protein Folding; Retinal Degeneration; Rhodopsin
PubMed: 31286171
DOI: 10.1007/s00232-019-00078-1 -
Trends in Cell Biology Nov 2020The light-sensitive outer segment organelle of the vertebrate photoreceptor cell is a modified cilium filled with hundreds of flattened 'disc' membranes that provide... (Review)
Review
The light-sensitive outer segment organelle of the vertebrate photoreceptor cell is a modified cilium filled with hundreds of flattened 'disc' membranes that provide vast light-absorbing surfaces. The outer segment is constantly renewed with new discs added at its base every day. This continuous process is essential for photoreceptor viability. In this review, we describe recent breakthroughs in the understanding of disc morphogenesis, with a focus on the molecular mechanisms responsible for initiating disc formation from the ciliary membrane. We highlight the discoveries that this mechanism evolved from an innate ciliary process of releasing small extracellular vesicles, or ectosomes, and that both disc formation and ectosome release rely on the actin cytoskeleton.
Topics: Actins; Animals; Cell-Derived Microparticles; Cilia; Humans; Models, Biological; Photoreceptor Cells; Polymerization
PubMed: 32900570
DOI: 10.1016/j.tcb.2020.08.005 -
Progress in Brain Research 2022For more than two centuries scientists and engineers have worked to understand and model how the eye encodes electromagnetic radiation (light). We now understand the...
For more than two centuries scientists and engineers have worked to understand and model how the eye encodes electromagnetic radiation (light). We now understand the principles of how light is transmitted through the optics of the eye and encoded by retinal photoreceptors and light-sensitive neurons. In recent years, new instrumentation has enabled scientists to measure the specific parameters of the optics and photoreceptor encoding. We implemented the principles and parameter estimates that characterize the human eye in an open-source software toolbox. This chapter describes the principles behind these tools and illustrates how to use them to compute the initial visual encoding.
Topics: Humans; Optics and Photonics; Photoreceptor Cells, Vertebrate; Retina; Retinal Cone Photoreceptor Cells; Software
PubMed: 35940717
DOI: 10.1016/bs.pbr.2022.04.006 -
Annual Review of Vision Science Sep 2019Rods and cones are retinal photoreceptor neurons required for our visual sensation. Because of their highly polarized structures and well-characterized processes of G... (Review)
Review
Rods and cones are retinal photoreceptor neurons required for our visual sensation. Because of their highly polarized structures and well-characterized processes of G protein-coupled receptor-mediated phototransduction signaling, these photoreceptors have been excellent models for studying the compartmentalization and sorting of proteins. Rods and cones have a modified ciliary compartment called the outer segment (OS) as well as non-OS compartments. The distinct membrane protein compositions between OS and non-OS compartments suggest that the OS is separated from the rest of the cellular compartments by multiple barriers or gates that are selectively permissive to specific cargoes. This review discusses the mechanisms of protein sorting and compartmentalization in photoreceptor neurons. Proper sorting and compartmentalization of membrane proteins are required for signal transduction and transmission. This review also discusses the roles of compartmentalized signaling, which is compromised in various retinal ciliopathies.
Topics: Eye Proteins; Humans; Membrane Proteins; Protein Transport; Retinal Cone Photoreceptor Cells; Retinal Degeneration; Retinal Rod Photoreceptor Cells; Signal Transduction; Vision, Ocular
PubMed: 31226015
DOI: 10.1146/annurev-vision-091718-014843 -
International Journal of Molecular... May 2021Retinoprotective proteins play important roles for retinal tissue integrity. They can directly affect the function and the survival of photoreceptors, and/or indirectly... (Review)
Review
Retinoprotective proteins play important roles for retinal tissue integrity. They can directly affect the function and the survival of photoreceptors, and/or indirectly target the retinal pigment epithelium (RPE) and endothelial cells that support these tissues. Retinoprotective proteins are used in basic, translational and in clinical studies to prevent and treat human retinal degenerative disorders. In this review, we provide an overview of proteins that protect the retina and focus on pigment epithelium-derived factor (PEDF), and its effects on photoreceptors, RPE cells, and endothelial cells. We also discuss delivery systems such as pharmacologic and genetic administration of proteins to achieve photoreceptor survival and retinal tissue integrity.
Topics: Animals; Endothelial Cells; Eye Proteins; Humans; Nerve Growth Factors; Photoreceptor Cells; Photoreceptor Cells, Vertebrate; Protein Transport; Retina; Retinal Degeneration; Retinal Neurons; Retinal Pigment Epithelium; Serpins
PubMed: 34069505
DOI: 10.3390/ijms22105344 -
International Journal of Molecular... Jul 2022Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and...
Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and autoimmune uveitis. However, while IL-35 is structurally and functionally similar to IL-27, the intrinsic roles of IL-35 in CNS tissues are unknown. Thus, we generated IL-35/YFP-knock-in reporter mice (p35-KI) and demonstrated that photoreceptor neurons constitutively secrete IL-35, which might protect the retina from persistent low-grade inflammation that can impair photoreceptor functions. Furthermore, the p35-KI mouse, which is hemizygous at the locus, develops more severe uveitis because of reduced IL-35 expression. Interestingly, onset and exacerbation of uveitis in p35-KI mice caused by extravasation of proinflammatory Th1/Th17 lymphocytes into the retina were preceded by a dramatic decrease of IL-35, attributable to massive death of photoreceptor cells. Thus, while inflammation-induced death of photoreceptors and loss of protective effects of IL-35 exacerbated uveitis, our data also suggest that constitutive production of IL-35 in the retina might have housekeeping functions that promote sterilization immunity in the neuroretina and maintain ocular immune privilege.
Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Gene Expression Regulation; Immune Privilege; Inflammation; Interleukin-27; Interleukins; Mice; Mice, Inbred C57BL; Photoreceptor Cells; Retina; Th17 Cells; Uveitis
PubMed: 35897732
DOI: 10.3390/ijms23158156 -
Progress in Retinal and Eye Research Sep 2022In the vertebrate retina, rods and cones both detect light, but they differ in functional aspects such as light sensitivity and temporal resolution, and in some cell... (Review)
Review
In the vertebrate retina, rods and cones both detect light, but they differ in functional aspects such as light sensitivity and temporal resolution, and in some cell biological aspects. For functional aspects, both types of photoreceptors use a phototransduction cascade, consisting of a series of enzymatic reactions, to convert photon capture to an electrical signal. To understand the mechanisms underlying the functional differences between rods and cones at the molecular level, we compared biochemically, each of the reactions in the phototransduction cascades of rods and cones using the cells isolated and purified from carp retina. Although the cascade proteins are identical or are functionally similar between rods and cones, their activities together with their expression levels are mostly different. In general, reactions that generate a response are somewhat less effective in cones than in rods, but each of the reactions for termination and recovery of a response are much more effective in cones. These findings explain lower light sensitivity and briefer light responses in cones than in rods. In addition, our considerations suggest that a Ca-binding protein, S-modulin or recoverin, has a currently unnoticed role in shaping light responses. Upon comparison of the expression levels of proteins and/or mRNAs using purified cells, several proteins were found to be specifically or predominantly expressed in cones. These proteins will be of interest in future studies aimed at characterizing the differences between rods and cones.
Topics: Animals; Humans; Light Signal Transduction; Photophobia; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells
PubMed: 34974196
DOI: 10.1016/j.preteyeres.2021.101040 -
Experimental Eye Research Oct 2020Inherited retinal degenerative disorders such as retinitis pigmentosa and Usher syndrome are characterized by progressive death of photoreceptor cells. To restore vision...
Inherited retinal degenerative disorders such as retinitis pigmentosa and Usher syndrome are characterized by progressive death of photoreceptor cells. To restore vision to patients blinded by these diseases, a stem cell-based photoreceptor cell replacement strategy will likely be required. Although retinal stem cell differentiation protocols suitable for generating photoreceptor cells exist, they often yield a rather heterogenous mixture of cell types. To enrich the donor cell population for one or a few cell types, scientists have traditionally relied upon the use of antibody-based selection approaches. However, these strategies are quite labor intensive and require animal derived reagents and equipment that are not well suited to current good manufacturing practices (cGMP). The purpose of this study was to develop and evaluate a microfluidic cell sorting device capable of exploiting the physical and mechanical differences between retinal cell types to enrich specific donor cell populations such as Retinal Pigment Epithelial (RPE) cells and photoreceptor cells. Using this device, we were able to separate a mixture of RPE and iPSC-derived photoreceptor precursor cell lines into two substantially enriched fractions. The enrichment factor of the RPE fraction was 2 and that of the photoreceptor precursor cell fraction was 2.7. Similarly, when human retina, obtained from 3 independent donors, was dissociated and passed through the sorting device, the heterogeneous mixture could be reliably sorted into RPE and photoreceptor cell rich fractions. In summary, microfluidic cell sorting is a promising approach for antibody free enrichment of retinal cell populations.
Topics: Animals; Cell Differentiation; Cell Line; Humans; Microfluidics; Microscopy, Atomic Force; Photoreceptor Cells; Retinal Degeneration; Retinal Pigment Epithelium
PubMed: 32771499
DOI: 10.1016/j.exer.2020.108166 -
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 -
Advances in Experimental Medicine and... 2023Retinitis pigmentosa (RP) causes blindness in 1 out of 3000-4000 individuals worldwide. Understanding the disease mechanism underlying the death of photoreceptors in RP... (Review)
Review
Retinitis pigmentosa (RP) causes blindness in 1 out of 3000-4000 individuals worldwide. Understanding the disease mechanism underlying the death of photoreceptors in RP patient is crucial for the discovery and development of therapies to prevent and stop the progression of retinal degeneration. Despite having provided valuable insight into RP pathology, several shortcomings of animal models warrant the need for a better modeling system. This review discusses the current use of patient-derived induced pluripotent stem cells (iPSCs) to model RP and its advantages over animal models. Further improvement to enhance the representativeness of iPSC RP models is also discussed.
Topics: Animals; Induced Pluripotent Stem Cells; Retinitis Pigmentosa; Retinal Degeneration; Photoreceptor Cells; Models, Animal; Retina
PubMed: 37440086
DOI: 10.1007/978-3-031-27681-1_81