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Survey of Ophthalmology 2020Retinitis pigmentosa 1-like 1 (RP1L1) is a component of the photoreceptor cilium. Pathogenic variants in RP1L1 lead to photoreceptor disease, suggesting an important... (Review)
Review
Retinitis pigmentosa 1-like 1 (RP1L1) is a component of the photoreceptor cilium. Pathogenic variants in RP1L1 lead to photoreceptor disease, suggesting an important role for RP1L1 in photoreceptor biology, though its exact function is unknown. To date, RP1L1 variants have been associated with occult macular dystrophy (a cone degeneration) and retinitis pigmentosa (a rod disease). Here, we summarize reported RP1L1-associated photoreceptor conditions and disease-causing RP1L1 variants. We also discuss novel associations between RP1L1 and additional photoreceptor conditions-besides occult macular dystrophy and retinitis pigmentosa-and fit RP1L1 into the broader scope of photoreceptor disease. RP1L1 appears to have a complex relationship with other photoreceptor proteins and may modify disease phenotype. Ultimately, further exploration of the relationship between RP1L1, other cilium components, and their impact on photoreceptor health is needed.
Topics: DNA; DNA Mutational Analysis; Electroretinography; Eye Proteins; Humans; Mutation; Phenotype; Retinal Cone Photoreceptor Cells; Retinal Diseases
PubMed: 32360662
DOI: 10.1016/j.survophthal.2020.04.005 -
Developmental Biology Aug 2021Synapses in the outer retina are the first information relay points in vision. Here, photoreceptors form synapses onto two types of interneurons, bipolar cells and... (Review)
Review
Synapses in the outer retina are the first information relay points in vision. Here, photoreceptors form synapses onto two types of interneurons, bipolar cells and horizontal cells. Because outer retina synapses are particularly large and highly ordered, they have been a useful system for the discovery of mechanisms underlying synapse specificity and maintenance. Understanding these processes is critical to efforts aimed at restoring visual function through repairing or replacing neurons and promoting their connectivity. We review outer retina neuron synapse architecture, neural migration modes, and the cellular and molecular pathways that play key roles in the development and maintenance of these connections. We further discuss how these mechanisms may impact connectivity in the retina.
Topics: Animals; Humans; Interneurons; Photoreceptor Cells; Retina; Retinal Cone Photoreceptor Cells; Retinal Horizontal Cells; Synapses; Vision, Ocular
PubMed: 33848537
DOI: 10.1016/j.ydbio.2021.04.001 -
Nature Aug 2023The concomitant occurrence of tissue growth and organization is a hallmark of organismal development. This often means that proliferating and differentiating cells are...
The concomitant occurrence of tissue growth and organization is a hallmark of organismal development. This often means that proliferating and differentiating cells are found at the same time in a continuously changing tissue environment. How cells adapt to architectural changes to prevent spatial interference remains unclear. Here, to understand how cell movements that are key for growth and organization are orchestrated, we study the emergence of photoreceptor neurons that occur during the peak of retinal growth, using zebrafish, human tissue and human organoids. Quantitative imaging reveals that successful retinal morphogenesis depends on the active bidirectional translocation of photoreceptors, leading to a transient transfer of the entire cell population away from the apical proliferative zone. This pattern of migration is driven by cytoskeletal machineries that differ depending on the direction: microtubules are exclusively required for basal translocation, whereas actomyosin is involved in apical movement. Blocking the basal translocation of photoreceptors induces apical congestion, which hampers the apical divisions of progenitor cells and leads to secondary defects in lamination. Thus, photoreceptor migration is crucial to prevent competition for space, and to allow concurrent tissue growth and lamination. This shows that neuronal migration, in addition to its canonical role in cell positioning, can be involved in coordinating morphogenesis.
Topics: Animals; Humans; Actomyosin; Cell Competition; Cell Differentiation; Cell Movement; Cell Proliferation; Microtubules; Morphogenesis; Organoids; Photoreceptor Cells; Retina; Zebrafish
PubMed: 37558872
DOI: 10.1038/s41586-023-06392-y -
The New Phytologist May 2024Phytochrome B (phyB) is a red and far-red photoreceptor that promotes light responses. Upon photoactivation, phyB enters the nucleus and forms a molecular condensate... (Review)
Review
Phytochrome B (phyB) is a red and far-red photoreceptor that promotes light responses. Upon photoactivation, phyB enters the nucleus and forms a molecular condensate called a photobody through liquid-liquid phase separation. Phytochrome B photobody comprises phyB, the main scaffold molecule, and at least 37 client proteins. These clients belong to diverse functional categories enriched with transcription regulators, encompassing both positive and negative light signaling factors, with the functional bias toward the negative factors. The functionally diverse clients suggest that phyB photobody acts either as a trap to capture proteins, including negatively acting transcription regulators, for processes such as sequestration, modification, or degradation or as a hub where proteins are brought into close proximity for interaction in a light-dependent manner.
Topics: Humans; Phytochrome B; Arabidopsis Proteins; Arabidopsis; Light; Photoreceptor Cells; Phytochrome
PubMed: 38477037
DOI: 10.1111/nph.19675 -
Contact Lens & Anterior Eye : the... Jun 2022
Topics: Cornea; Corneal Topography; Humans; Keratoconus; Retinal Cone Photoreceptor Cells
PubMed: 35210169
DOI: 10.1016/j.clae.2022.101578 -
Bulletin of Experimental Biology and... May 2021We developed a model of retinal degeneration in rabbits based on exposure to light with a wavelength of 405 nm. This model allows reproducing structural and functional...
We developed a model of retinal degeneration in rabbits based on exposure to light with a wavelength of 405 nm. This model allows reproducing structural and functional disorders in the central parts of the retina, including primarily degeneration of the outer layers of the retina (retinal pigment epithelium and layer of photoreceptor cells), and is designed to study the mechanisms of formation, progression and effectiveness of new drugs and methods of treatment of degenerative diseases of the retina.
Topics: Adaptation, Ocular; Animals; Disease Models, Animal; Light; Male; Photoreceptor Cells; Rabbits; Retina; Retinal Degeneration
PubMed: 34173098
DOI: 10.1007/s10517-021-05213-4 -
Pflugers Archiv : European Journal of... Sep 2021The rod and cone photoreceptor cells of the vertebrate retina have highly specialized structures that enable them to carry out their function of light detection over a... (Review)
Review
The rod and cone photoreceptor cells of the vertebrate retina have highly specialized structures that enable them to carry out their function of light detection over a broad range of illumination intensities with optimized spatial and temporal resolution. Most prominent are their unusually large sensory cilia, consisting of outer segments packed with photosensitive disc membranes, a connecting cilium with many features reminiscent of the primary cilium transition zone, and a pair of centrioles forming a basal body which serves as the platform upon which the ciliary axoneme is assembled. These structures form a highway through which an enormous flux of material moves on a daily basis to sustain the continual turnover of outer segment discs and the energetic demands of phototransduction. After decades of study, the details of the fine structure and distribution of molecular components of these structures are still incompletely understood, but recent advances in cellular imaging techniques and animal models of inherited ciliary defects are yielding important new insights. This knowledge informs our understanding both of the mechanisms of trafficking and assembly and of the pathophysiological mechanisms of human blinding ciliopathies.
Topics: Animals; Cilia; Humans; Retinal Cone Photoreceptor Cells; Retinal Photoreceptor Cell Inner Segment; Retinal Photoreceptor Cell Outer Segment
PubMed: 34050409
DOI: 10.1007/s00424-021-02564-9 -
Pflugers Archiv : European Journal of... Sep 2021In the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract... (Review)
Review
In the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.
Topics: Animals; Gap Junctions; Humans; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Synapses
PubMed: 33988778
DOI: 10.1007/s00424-021-02572-9 -
Annual Review of Vision Science Sep 2021Our sense of sight relies on photoreceptors, which transduce photons into the nervous system's electrochemical interpretation of the visual world. These precious... (Review)
Review
Our sense of sight relies on photoreceptors, which transduce photons into the nervous system's electrochemical interpretation of the visual world. These precious photoreceptors can be disrupted by disease, injury, and aging. Once photoreceptors start to die, but before blindness occurs, the remaining retinal circuitry can withstand, mask, or exacerbate the photoreceptor deficit and potentially be receptive to newfound therapies for vision restoration. To maximize the retina's receptivity to therapy, one must understand the conditions that influence the state of the remaining retina. In this review, we provide an overview of the retina's structure and function in health and disease. We analyze a collection of observations on photoreceptor disruption and generate a predictive model to identify parameters that influence the retina's response. Finally, we speculate on whether the retina, with its remarkable capacity to function over light levels spanning nine orders of magnitude, uses these same adaptational mechanisms to withstand and perhaps mask photoreceptor loss.
Topics: Photoreceptor Cells; Retina
PubMed: 34524879
DOI: 10.1146/annurev-vision-100119-124713 -
Journal of Lipid Research 2021Photoreceptors have high energy demands and a high density of mitochondria that produce ATP through oxidative phosphorylation (OXPHOS) of fuel substrates. Although... (Review)
Review
Photoreceptors have high energy demands and a high density of mitochondria that produce ATP through oxidative phosphorylation (OXPHOS) of fuel substrates. Although glucose is the major fuel for CNS brain neurons, in photoreceptors (also CNS), most glucose is not metabolized through OXPHOS but is instead metabolized into lactate by aerobic glycolysis. The major fuel sources for photoreceptor mitochondria remained unclear for almost six decades. Similar to other tissues (like heart and skeletal muscle) with high metabolic rates, photoreceptors were recently found to metabolize fatty acids (palmitate) through OXPHOS. Disruption of lipid entry into photoreceptors leads to extracellular lipid accumulation, suppressed glucose transporter expression, and a duel lipid/glucose fuel shortage. Modulation of lipid metabolism helps restore photoreceptor function. However, further elucidation of the types of lipids used as retinal energy sources, the metabolic interaction with other fuel pathways, as well as the cross-talk among retinal cells to provide energy to photoreceptors is not fully understood. In this review, we will focus on the current understanding of photoreceptor energy demand and sources, and potential future investigations of photoreceptor metabolism.
Topics: Photoreceptor Cells
PubMed: 32094231
DOI: 10.1194/jlr.TR120000618