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The Journal of Neuroscience : the... Aug 1997The hedgehog gene family encodes secreted proteins important in many developmental patterning events in both vertebrates and invertebrates. In the Drosophila eye disk,...
The hedgehog gene family encodes secreted proteins important in many developmental patterning events in both vertebrates and invertebrates. In the Drosophila eye disk, hedgehog controls the progression of photoreceptor differentiation in the morphogenetic furrow. To investigate whether hedgehog proteins are also involved in the development of the vertebrate retina at stages of photoreceptor differentiation, we analyzed expression of the three known vertebrate hedgehog genes. We found that Sonic hedgehog and Desert hedgehog are expressed in the developing retina, albeit at very low levels, whereas Indian hedgehog (Ihh) is expressed in the developing and mature retinal pigmented epithelium, beginning at embryonic day 13. To determine whether hedgehog proteins have activities on developing retinal cells, we used an in vitro system in which much of retinal histogenesis is recapitulated. N-terminal recombinant Sonic Hedgehog protein (SHH-N) was added to rat retinal cultures for 3-12 d, and the numbers of retinal cells of various phenotypes were analyzed by immunohistochemistry. We found that SHH-N caused a transient increase in the number of retinal progenitor cells, and a 2- to 10-fold increase in the number of photoreceptors differentiating in the cultures when analyzed with three different photoreceptor-specific antigens. In contrast, the numbers of retinal ganglion cells and amacrine cells were similar to those in control cultures. These results show that Hedgehog proteins can regulate mitogenesis and photoreceptor differentiation in the vertebrate retina, and Ihh is a candidate factor from the pigmented epithelium to promote retinal progenitor proliferation and photoreceptor differentiation.
Topics: Animals; Animals, Newborn; Cell Differentiation; Cells, Cultured; Drosophila Proteins; Embryonic Induction; Eye; Female; Fetus; Hedgehog Proteins; Insect Proteins; Mammals; Pregnancy; Proteins; RNA, Messenger; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Retinal Rod Photoreceptor Cells; Stem Cells; Trans-Activators
PubMed: 9236238
DOI: 10.1523/JNEUROSCI.17-16-06277.1997 -
Current Opinion in Neurobiology Aug 1994Rod and cone photoreceptors respond to light with distinct sensitivity and kinetics. Recent biochemical and electrophysiological studies demonstrate that the enzymes of... (Review)
Review
Rod and cone photoreceptors respond to light with distinct sensitivity and kinetics. Recent biochemical and electrophysiological studies demonstrate that the enzymes of the phototransduction cascade are similar, but not identical, in these two photoreceptor types. In contrast, light or voltage stimulation generates changes in the cytoplasmic concentration of Ca2+ in the outer segment that are far larger and faster in cones than in rods. This distinction reflects rod-cone differences in each of the elements that control Ca2+ homeostasis: cell volume, the rate of Ca2+ clearance from the outer segment, the cytoplasmic Ca2+ buffering, and the Ca2+ influx through cGMP-gated ion channels.
Topics: Animals; Calcium; Homeostasis; Humans; Photochemistry; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Signal Transduction
PubMed: 7812136
DOI: 10.1016/0959-4388(94)90048-5 -
Experimental Eye Research Jun 2021Retinal regeneration research offers hope to people affected by visual impairment due to disease and injury. Ongoing research has explored many avenues towards retinal...
Retinal regeneration research offers hope to people affected by visual impairment due to disease and injury. Ongoing research has explored many avenues towards retinal regeneration, including those that utilizes implantation of devices, cells or targeted viral-mediated gene therapy. These results have so far been limited, as gene therapy only has applications for rare single-gene mutations and implantations are invasive and in the case of cell transplantation donor cells often fail to integrate with adult neurons. An alternative mode of retinal regeneration utilizes a stem cell population unique to vertebrate retina - Müller glia (MG). Endogenous MG can readily regenerate lost neurons spontaneously in zebrafish and to a very limited extent in mammalian retina. The use of adenosine triphosphate (ATP) has been shown to induce retinal degeneration and activation of the MG in mammals, but whether this is conserved to other vertebrate species including those with higher regenerative capacity remains unknown. In our study, we injected a single dose of ATP intravitreal in zebrafish to characterize the cell death and MG induced regeneration. We used TUNEL labelling on retinal sections to show that ATP caused localised death of photoreceptors and ganglion cells within 24 h. Histology of GFP-transgenic zebrafish and BrdU injected fish demonstrated that MG proliferation peaked at days 3 and 4 post-ATP injection. Using BrdU labelling and photoreceptor markers (Zpr1) we observed regeneration of lost rod photoreceptors at day 14. This study has been undertaken to allow for comparative studies between mammals and zebrafish that use the same specific induction method of injury, i.e. ATP induced injury to allow for direct comparison of across species to narrow down resulting differences that might reflect the differing regenerative capacity. The ultimate aim of this work is to recapitulate pro-neurogenesis Müller glia signaling in mammals to produce new neurons that integrate with the existing retinal circuit to restore vision.
Topics: Adenosine Triphosphate; Animals; Apoptosis; Cell Proliferation; Disease Models, Animal; Ependymoglial Cells; Female; In Situ Nick-End Labeling; Intravitreal Injections; Male; Nerve Regeneration; Neuroglia; Retinal Degeneration; Retinal Ganglion Cells; Retinal Rod Photoreceptor Cells; Zebrafish
PubMed: 33839111
DOI: 10.1016/j.exer.2021.108569 -
Journal of the Optical Society of... Mar 2016We determined how rod signaling at mesopic light levels is altered by extrinsic temporal white noise that is correlated or uncorrelated with the activity of one...
We determined how rod signaling at mesopic light levels is altered by extrinsic temporal white noise that is correlated or uncorrelated with the activity of one (magnocellular, parvocellular, or koniocellular) postreceptoral pathway. Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. Psychometric (Weibull) functions were measured for incremental rod pulses (50 to 250 ms) in the presence (or absence; control) of perceptually invisible subthreshold extrinsic noise. Uncorrelated (rod) noise facilitates rod detection. Correlated postreceptoral pathway noise produces differential changes in rod detection thresholds and decreases the slope of the psychometric functions. We demonstrate that invisible extrinsic noise changes rod-signaling characteristics within the three retinogeniculate pathways at mesopic illumination depending on the temporal profile of the rod stimulus and the extrinsic noise type.
Topics: Adult; Humans; Light; Male; Models, Biological; Psychometrics; Retinal Rod Photoreceptor Cells; Rod-Cone Interaction; Signal Transduction; Time Factors
PubMed: 26974946
DOI: 10.1364/JOSAA.33.000A93 -
Progress in Retinal and Eye Research Jul 2009Although outnumbered more than 20:1 by rod photoreceptors, cone cells in the human retina mediate daylight vision and are critical for visual acuity and color... (Review)
Review
Although outnumbered more than 20:1 by rod photoreceptors, cone cells in the human retina mediate daylight vision and are critical for visual acuity and color discrimination. A variety of human diseases are characterized by a progressive loss of cone photoreceptors but the low abundance of cones and the absence of a macula in non-primate mammalian retinas have made it difficult to investigate cones directly. Conventional rodents (laboratory mice and rats) are nocturnal rod-dominated species with few cones in the retina, and studying other animals with cone-rich retinas presents various logistic and technical difficulties. Originating in the early 1900s, past research has begun to provide insights into cone ultrastructure but has yet to afford an overall perspective of cone cell organization. This review summarizes our past progress and focuses on the recent introduction of special mammalian models (transgenic mice and diurnal rats rich in cones) that together with new investigative techniques such as atomic force microscopy and cryo-electron tomography promise to reveal a more unified concept of cone photoreceptor organization and its role in retinal diseases.
Topics: Animals; Electron Microscope Tomography; Humans; Mice; Mice, Transgenic; Microscopy, Atomic Force; Models, Animal; Rats; Retinal Cone Photoreceptor Cells; Retinal Diseases; Retinal Rod Photoreceptor Cells; Vision, Ocular
PubMed: 19501669
DOI: 10.1016/j.preteyeres.2009.05.003 -
The Journal of Neuroscience : the... Dec 2011The protein kinase C (PKC) family of enzymes regulates cell physiology through phosphorylation of serine and threonine residues of many proteins in most cell types. Here...
The protein kinase C (PKC) family of enzymes regulates cell physiology through phosphorylation of serine and threonine residues of many proteins in most cell types. Here we identify PKC-β1 and PKC-γ as isoforms that are essential for rod photoreceptor differentiation in mouse retinas. Using ex vivo retinal explants, we found that phorbol ester 12-myristate 13-acetate and insulin-like growth factor 1 (IGF1) induced rod differentiation, as defined by opsin or Crx expression, in a PKC-dependent manner days ahead of rod development in untreated explants. PKC-β1 and PKC-γ were colocalized with proliferating cell nuclear antigen (PCNA)- and STAT3-positive progenitors through the later differentiation period. Pharmacological or genetic inhibition of either isoform resulted in a partial reduction in the appearance of rods, whereas removing both isoforms resulted in their complete absence. Furthermore, a significant decline of STAT3 tyrosine phosphorylation was observed by activation of PKC, while inhibition of PKC resulted in an increase of phosphorylated STAT3 along with a delayed cell cycle exit of progenitors with prolonged PCNA expression. In adult retinas, IGF1 activates PI-3 kinase (PI3K), but in neonatal retinas its action is identical to the action of an PI3K inhibitor. These data unveil a novel signaling cascade that coordinates and regulates rod differentiation through specific PKC isoforms in mammals.
Topics: Animals; Cell Differentiation; Cells, Cultured; Insulin-Like Growth Factor I; Isoenzymes; Mice; Mice, Knockout; Phosphorylation; Protein Kinase C; Retinal Rod Photoreceptor Cells; Signal Transduction; Tetradecanoylphorbol Acetate
PubMed: 22171059
DOI: 10.1523/JNEUROSCI.2578-11.2011 -
The Journal of Physiology Jun 2017
Topics: Adaptation, Physiological; Photoreceptor Cells; Retinal Rod Photoreceptor Cells
PubMed: 28261801
DOI: 10.1113/JP274146 -
Developmental Dynamics : An Official... Oct 2008In postembryonic zebrafish, rod photoreceptors are continuously generated from progenitors in the inner nuclear layer, which are derived from radial Müller glia that...
In postembryonic zebrafish, rod photoreceptors are continuously generated from progenitors in the inner nuclear layer, which are derived from radial Müller glia that express the transcription factor pax6. We used BrdU incorporation, in combination with in situ hybridization for cell-specific transcription factors, to establish the patterns of gene expression during rod lineage maturation in the embryonic zebrafish. Downregulation of pax6 expression was accompanied by sporadic upregulation of expression of the transcription factors NeuroD/nrd, rx1, crx, and Nr2e3/pnr. As cells of the rod lineage entered the outer nuclear layer, they became homogeneous, coordinately expressing NeuroD, rx1, crx, and Nr2e3. Postmitotic, maturing rods also expressed nrl, rod opsin, and rod transducin/gnat1. The presence of rx1 within the rod lineage and in maturing rods indicates that rx1 is not cone-specific, as previously reported, and suggests a high degree of molecular similarity between rod and cone progenitor populations in the zebrafish.
Topics: Animals; Animals, Genetically Modified; Biomarkers; Bromodeoxyuridine; Cell Lineage; Cell Proliferation; Gene Expression Regulation, Developmental; Homeodomain Proteins; Kinetics; Retinal Rod Photoreceptor Cells; Transcription Factors; Zebrafish; Zebrafish Proteins
PubMed: 18816851
DOI: 10.1002/dvdy.21721 -
Methods in Molecular Biology (Clifton,... 2015The connecting cilium of the rod photoreceptor is a tubular structure that bridges two adjacent cellular compartments, the inner segment, the major site of biosynthesis...
The connecting cilium of the rod photoreceptor is a tubular structure that bridges two adjacent cellular compartments, the inner segment, the major site of biosynthesis and energy metabolism, and the outer segment, a highly specialized ciliary structure responsible for phototransduction. The connecting cilium allows for active processes of protein sorting and transport to occur between them. Mutations affecting the cargo, their transporters, and the structural components of the primary cilium and basal body lead to aberrant trafficking and photoreceptor cell death. Understanding the overall design of the cilium, its architectural organization, and the function of varied protein complexes within the structural hierarchy of the cilium requires techniques for visualizing their native three-dimensional structures at high magnification. Here we describe methods for isolating retinas from mice, purifying fragments of rod cells that include much of the inner segment and the rod photoreceptor cilia, vitrifying the cell fragments, and determining their structures by cryo-electron tomography.
Topics: Animals; Cilia; Cryoelectron Microscopy; Mice; Retina; Retinal Rod Photoreceptor Cells; Rod Cell Outer Segment
PubMed: 25697530
DOI: 10.1007/978-1-4939-2330-4_18 -
The Journal of Cell Biology Sep 2010Humans possess the remarkable ability to perceive color, shape, and motion, and to differentiate between light intensities varied by over nine orders of magnitude.... (Review)
Review
Humans possess the remarkable ability to perceive color, shape, and motion, and to differentiate between light intensities varied by over nine orders of magnitude. Phototransduction--the process in which absorbed photons are converted into electrical responses--is the first stage of visual processing, and occurs in the outer segment, the light-sensing organelle of the photoreceptor cell. Studies of genes linked to human inherited blindness have been crucial to understanding the biogenesis of the outer segment and membrane-trafficking of photoreceptors.
Topics: Animals; Cellular Senescence; Eye; Humans; Morphogenesis; Retinal Rod Photoreceptor Cells; Rhodopsin; Vision, Ocular
PubMed: 20855501
DOI: 10.1083/jcb.201006020