-
The Journal of Neuroscience : the... May 1998We have conducted a comprehensive analysis of the relative timing of the terminal mitosis and the onset of rhodopsin expression in rod precursors in the rat retina in...
We have conducted a comprehensive analysis of the relative timing of the terminal mitosis and the onset of rhodopsin expression in rod precursors in the rat retina in vivo. This analysis demonstrated that there are two distinct phases of rod development during retinal histogenesis. For the majority of rod precursors, those born on or after embryonic day 19 (E19), the onset of rhodopsin expression was strongly correlated temporally with cell cycle withdrawal. For these precursors, the lag between the terminal mitosis and rhodopsin expression was measured to be 5.5-6.5 d on average. By contrast, for rod precursors born before E19, the lag was measured to be significantly longer, averaging from 8.5 to 12.5 d. In addition, these early-born rod precursors seemed to initiate rhodopsin expression in a manner that was not correlated temporally with the terminal mitosis. In these cells, onset of rhodopsin expression appeared approximately synchronous with later-born cells, suggesting a synchronous recruitment to the rod cell fate induced by environmental signals. To examine this possibility, experiments in which the early-born precursors were exposed to a late environment were conducted, using a reaggregate culture system. In these experiments, the early-born precursors appeared remarkably uninfluenced by the late environment with respect to both rod determination and the kinetics of rhodopsin expression. These results support the idea that intrinsically distinct populations of rod precursors constitute the two phases of rod development and that the behavior exhibited by the early-born precursors is intrinsically programmed.
Topics: Animals; Animals, Newborn; Cell Differentiation; Cells, Cultured; Cohort Studies; Female; Gestational Age; Kinetics; Pregnancy; Rats; Rats, Sprague-Dawley; Retinal Rod Photoreceptor Cells; Rhodopsin; S Phase; Stem Cells; Thymidine; Tritium
PubMed: 9570804
DOI: 10.1523/JNEUROSCI.18-10-03738.1998 -
PloS One 2018The retinal rod pathway, featuring dedicated rod bipolar cells (RBCs) and AII amacrine cells, has been intensely studied in placental mammals. Here, we analyzed the rod...
The retinal rod pathway, featuring dedicated rod bipolar cells (RBCs) and AII amacrine cells, has been intensely studied in placental mammals. Here, we analyzed the rod pathway in a nocturnal marsupial, the South American opossum Monodelphis domestica to elucidate whether marsupials have a similar rod pathway. The retina was dominated by rods with densities of 338,000-413,000/mm². Immunohistochemistry for the RBC-specific marker protein kinase Cα (PKCα) and the AII cell marker calretinin revealed the presence of both cell types with their typical morphology. This is the first demonstration of RBCs in a marsupial and of the integration of RBCs and AII cells in the rod signaling pathway. Electron microscopy showed invaginating synaptic contacts of the PKCα-immunoreactive bipolar cells with rods; light microscopic co-immunolabeling for the synaptic ribbon marker CtBP2 confirmed dominant rod contacts. The RBC axon terminals were mostly located in the innermost stratum S5 of the inner plexiform layer (IPL), but had additional side branches and synaptic varicosities in strata S3 and S4, with S3-S5 belonging to the presumed functional ON sublayer of the IPL, as shown by immunolabeling for the ON bipolar cell marker Gγ13. Triple-immunolabeling for PKCα, calretinin and CtBP2 demonstrated RBC synapses onto AII cells. These features conform to the pattern seen in placental mammals, indicating a basically similar rod pathway in M. domestica. The density range of RBCs was 9,900-16,600/mm2, that of AII cells was 1,500-3,260/mm2. The numerical convergence (density ratio) of 146-156 rods to 4.7-6.0 RBCs to 1 AII cell is within the broad range found among placental mammals. For comparison, we collected data for the Australian nocturnal dunnart Sminthopsis crassicaudata, and found it to be similar to M. domestica, with rod-contacting PKCα-immunoreactive bipolar cells that had axon terminals also stratifying in IPL strata S3-S5.
Topics: Animals; Marsupialia; Night Vision; Protein Kinase C; Retinal Rod Photoreceptor Cells; Synapses
PubMed: 30157204
DOI: 10.1371/journal.pone.0202089 -
Journal of the Optical Society of... Oct 2022We assessed how rod excitation (R) affects luminance (L + M + S) and chromatic [L/(L + M)] reaction times (RTs). A four-primary display based on the overlapped images of...
We assessed how rod excitation (R) affects luminance (L + M + S) and chromatic [L/(L + M)] reaction times (RTs). A four-primary display based on the overlapped images of two spectrally modified monitors, which allowed specific or combined [L + M + S + R, L/(L + M) + R] photoreceptor stimulation, was used to present a C-target stimulus differing from the background only by the selected stimulation. For the luminance pathway, rod input increased RTs, suggesting a suppressive rod-cone interaction. The responses of the chromatic pathway were faster when rods were involved, suggesting a major role of rods in mesopic color perception.
Topics: Color Perception; Photic Stimulation; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod-Cone Interaction; Vision, Ocular
PubMed: 36215550
DOI: 10.1364/JOSAA.462581 -
Documenta Ophthalmologica. Advances in... Jan 2003Age-related macular degeneration (AMD) is a main causes of severe visual impairment in the elderly in industrialized countries. The pathogenesis of this complex diseases... (Review)
Review
Age-related macular degeneration (AMD) is a main causes of severe visual impairment in the elderly in industrialized countries. The pathogenesis of this complex diseases is largely unknown, even though clinical characteristics and histopathology are well described. Because several aging changes are identical to those observed in AMD, there appears to exist an unknown switch mechanism from normal ageing to disease. Recent anatomical studies using elegant innovative techniques reveal that there is a 30% rod loss in normal ageing, which is increased in early AMD. Those and other observations by Curcio and co-workers indicate that early rod loss is an important denominator of AMD (Curcio CA. Eye 2001; 15:376). As in retinitis pigmentosa (RP), rods appear to die by apoptosis. Thus it seems mandatory to study the regulation of rod cell death in animal models to unravel possible mechanisms of rod loss in AMD. Our laboratory investigates signal transduction pathways and gene regulation of rod death in our model of light-induced apoptosis. The transcription factor AP1 is essential, whereas other classical pro- and antiapoptotic genes appear to be less important in our model system. Caspase-1 gene expression is distinctly upregulated after light exposure and there are several factors which completely protect against light-induced cell death, such as the anesthetic halothane, dexamethasone and the absence of bleachable rhodopsin during light exposure. A fast rhodopsin regeneration rate increased damage susceptibility. Our data indicate that rhodopsin is essential for the initiation of light-induced rod loss. Following photon absorption, there may be the generation of photochemically active molecules wich then induce the apoptotic death cascade.
Topics: Animals; Apoptosis; Caspase 1; Gene Expression; Humans; RNA, Messenger; Retinal Degeneration; Retinal Rod Photoreceptor Cells; Transcription Factor AP-1; Vision, Ocular
PubMed: 12675482
DOI: 10.1023/a:1022423724376 -
The Journal of Biological Chemistry Jan 2012Activation of the visual pigment by light in rod and cone photoreceptors initiates our visual perception. As a result, the signaling properties of visual pigments,... (Review)
Review
Activation of the visual pigment by light in rod and cone photoreceptors initiates our visual perception. As a result, the signaling properties of visual pigments, consisting of a protein, opsin, and a chromophore, 11-cis-retinal, play a key role in shaping the light responses of photoreceptors. The combination of pharmacological, physiological, and genetic tools has been a powerful approach advancing our understanding of the interactions between opsin and chromophore and how they affect the function of visual pigments. The signaling properties of the visual pigments modulate many aspects of the function of rods and cones, producing their unique physiological properties.
Topics: Animals; Humans; Opsins; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Retinaldehyde; Signal Transduction; Vision, Ocular
PubMed: 22074928
DOI: 10.1074/jbc.R111.303008 -
Investigative Ophthalmology & Visual... May 2003To investigate the role of glial-cell-line-derived neurotrophic factor (GDNF) on proliferation, differentiation, and apoptosis of different retinal cell types--in...
PURPOSE
To investigate the role of glial-cell-line-derived neurotrophic factor (GDNF) on proliferation, differentiation, and apoptosis of different retinal cell types--in particular, photoreceptor cells.
METHODS
Reaggregated histotypic spheres, derived from retinal cells of the E6 chicken embryo were used. Under rotation, so-called rosetted spheroids arose by aggregation of dissociated retinal cells, followed by the proliferation, migration, differentiation and programmed cell death of particular cell types. Rosetted spheroids were cultured under serum-reduced conditions, either in the absence or presence of 50 ng/mL GDNF. At appropriate stages, rosetted spheroids were analyzed by using conventional staining and immunolabeling with antibodies against different retinal cell types.
RESULTS
At early stages of culture, the application of GDNF to rosetted spheroids significantly increased and sustained the rate of proliferation. In particular, a de novo production of rod photoreceptors was observed, whereas cone photoreceptors and amacrine, horizontal, ganglion, and Müller cells were not affected. In addition, in GDNF-treated cultures, rod photoreceptors differentiated earlier than in nontreated cultures. In older rosetted spheroids raised in absence of GDNF, rod but not cone photoreceptors underwent apoptosis. By supplementation with GDNF, the percentage of dying rod photoreceptors was dramatically reduced (31%-6% at 8 days in culture, 71%-3% at 10 days in culture). Both the mitogenic and survival promoting effect of GDNF were dose dependent.
CONCLUSIONS
The results strongly suggest that GDNF, at least in vitro, affects rod photoreceptors. Depending on the developmental stage, GDNF regulates their proliferation, differentiation, and survival.
Topics: Animals; Apoptosis; Cell Count; Cell Differentiation; Cell Division; Cell Survival; Chick Embryo; Dose-Response Relationship, Drug; Fluorescent Antibody Technique, Indirect; Glial Cell Line-Derived Neurotrophic Factor; Nerve Growth Factors; Neuroprotective Agents; Retinal Rod Photoreceptor Cells; Spheroids, Cellular
PubMed: 12714664
DOI: 10.1167/iovs.02-0915 -
The Journal of Neuroscience : the... Mar 2005How and when positional identities in the neural retina are established have been addressed primarily with respect to the topographic projections of retinal ganglion... (Comparative Study)
Comparative Study
How and when positional identities in the neural retina are established have been addressed primarily with respect to the topographic projections of retinal ganglion cells onto their targets in the brain. Although retinotectal map formation is a prominent manifestation of retinal patterning, it is not the only one. Photoreceptor subtypes are arranged in distinct, species-specific patterns. The mechanisms used to establish photoreceptor patterns have been relatively unexplored at the mechanistic level. We performed ablations of the eye anlage in chickens and found that removal of the anterior or dorsal optic vesicle caused loss of the area centralis, which is a rod-free central area of the retina, and severely disorganized other aspects of the rod pattern. These observations indicate that the anteroposterior and dorsoventral distribution of rods is determined by the optic vesicle stage. To investigate the molecular mechanisms involved, the rod distribution was analyzed after viral misexpression of several patterning genes that were previously shown to be important in positional specification of retinal ganglion cells. Ectopic expression of FoxG1, SOHo1,or GH6 transcription factors expressed in the anterior optic vesicle and/or optic cup, respectively, did not affect the rod pattern. This pattern therefore appears to be specified by an activity acting before, or in parallel with, these factors. In contrast, misexpression of the ventrally restricted transcription factor, cVax, severely disturbed the rod pattern.
Topics: Animals; Avian Proteins; Body Patterning; Chick Embryo; Denervation; Forkhead Transcription Factors; Gene Expression; Gene Expression Regulation, Developmental; Homeodomain Proteins; In Situ Hybridization; Nerve Tissue Proteins; Receptor, EphA3; Retinal Rod Photoreceptor Cells
PubMed: 15772342
DOI: 10.1523/JNEUROSCI.2037-04.2005 -
The Journal of Neuroscience : the... Apr 2021Rod photoreceptors can be saturated by exposure to bright background light, so that no flash superimposed on the background can elicit a detectable response. This...
Rod photoreceptors can be saturated by exposure to bright background light, so that no flash superimposed on the background can elicit a detectable response. This phenomenon, called increment saturation, was first demonstrated psychophysically by Aguilar and Stiles and has since been shown in many studies to occur in single rods. Recent experiments indicate, however, that rods may be able to avoid saturation under some conditions of illumination. We now show in electroretinogram and single-cell recordings that in continuous and prolonged exposure even to very bright light, the rods of mice from both sexes recover as much as 15% of their dark current and that responses can persist for hours. In parallel to recovery of outer segment current is an ∼10-fold increase in the sensitivity of rod photoresponses. This recovery is decreased in transgenic mice with reduced light-dependent translocation of the G protein transducin. The reduction in outer-segment transducin together with a novel mechanism of visual-pigment regeneration within the rod itself enable rods to remain responsive over the whole of the physiological range of vision. In this way, rods are able to avoid an extended period of transduction channel closure, which is known to cause photoreceptor degeneration. Rods are initially saturated in bright light so that no flash superimposed on the background can elicit a detectable response. Frederiksen and colleagues show in whole retina and single-cell recordings that, if the background light is prolonged, rods slowly recover and can continue to produce significant responses over the entire physiological range of vision. Response recovery occurs by translocation of the G protein transducin from the rod outer to the inner segment, together with a novel mechanism of visual-pigment regeneration within the rod itself. Avoidance of saturation in bright light may be one of the principal mechanisms the retina uses to keep rod outer-segment channels from ever closing for too long a time, which is known to produce photoreceptor degeneration.
Topics: Animals; Electroretinography; Female; Light; Male; Mice; Protein Transport; Retinal Rod Photoreceptor Cells; Single-Cell Analysis; Transducin; Vision, Ocular
PubMed: 33593858
DOI: 10.1523/JNEUROSCI.2817-20.2021 -
Regenerative Medicine Sep 2012
Topics: Animals; Retinal Rod Photoreceptor Cells; Vision, Ocular
PubMed: 22954431
DOI: 10.2217/rme.12.56 -
Biophysical Journal Sep 2002Eukaryotic cells use membrane organelles, like the endoplasmic reticulum or the Golgi, to carry out different functions. Vertebrate rod photoreceptors use hundreds of...
Eukaryotic cells use membrane organelles, like the endoplasmic reticulum or the Golgi, to carry out different functions. Vertebrate rod photoreceptors use hundreds of membrane sacs (the disks) for the detection of light. We have used fluorescent tracers and single cell imaging to study the properties of rod photoreceptor disks. Labeling of intact rod photoreceptors with membrane markers and polar tracers revealed communication between intradiskal and extracellular space. Internalized tracers moved along the length of the rod outer segment, indicating communication between the disks as well. This communication involved the exchange of both membrane and aqueous phase and had a time constant in the order of minutes. The communication pathway uses approximately 2% of the available membrane disk area and does not allow the passage of molecules larger than 10 kDa. It was possible to load the intradiskal space with fluorescent Ca(2+) and pH dyes, which reported an intradiskal Ca(2+) concentration in the order of 1 microM and an acidic pH 6.5, both of them significantly different than intracellular and extracellular Ca(2+) concentrations and pH. The results suggest that the rod photoreceptor disks are not discrete, passive sacs but rather comprise an active cellular organelle. The communication between disks may be important for membrane remodeling as well as for providing access to the intradiskal space of the whole outer segment.
Topics: Animals; Biophysical Phenomena; Biophysics; Calcium; Calibration; Diffusion; Fluorescent Dyes; Hydrogen-Ion Concentration; Microscopy, Fluorescence; Retinal Rod Photoreceptor Cells; Time Factors; Urodela
PubMed: 12202366
DOI: 10.1016/S0006-3495(02)73911-8