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Results for “Retinal Rod Photoreceptor Cells”

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PubMed1998

A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene.

Mutations in the retinal-expressed gene CRX (cone-rod homeobox gene) have been associated with dominant cone-rod dystrophy and with de novo Leber congenital amaurosis. However, CRX is a transcription factor for several retinal genes, including the opsins and the gene for interphotoreceptor retinoid binding protein. Because loss of CRX function could alter the expression of a number of other retinal proteins, we screened for mutations in the CRX gene in probands with a range of degenerative retinal diseases. Of the 294 unrelated individuals screened, we identified four CRX mutations in families with clinical diagnoses of autosomal dominant cone-rod dystrophy, late-onset dominant retinitis pigmentosa, or dominant congenital Leber amaurosis (early-onset retinitis pigmentosa), and we identified four additional benign sequence variants. These findings imply that CRX mutations may be associated with a wide range of clinical phenotypes, including congenital retinal dystrophy (Leber) and progressive diseases such as cone-rod dystrophy or retinitis pigmentosa, with a wide range of onset.

Amino Acid Substitution↗
PubMed2003

Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration.

Many gaps exist in our knowledge of human retinal microglia in health and disease. We address the hypothesis that primary death of rod photoreceptors leads to activation of resident microglia in human retinas with retinitis pigmentosa (RP), late-onset retinal degeneration (L-ORD), or age-related macular degeneration (AMD). Regions of ongoing photoreceptor cell death were studied by immunocytochemistry with microglia- and other retinal cell-specific markers. In normal human retinas, quiescent microglia were small, stellate cells associated with inner retinal blood vessels. In retinas with RP, L-ORD, or AMD, numerous activated microglia were present in the outer nuclear layer in regions of ongoing rod cell death. These microglia were enlarged, amoeboid cells that contained rhodopsin-positive cytoplasmic inclusions. We conclude that activated microglia migrate to the outer nuclear layer and remove rod cell debris. In other central nervous system diseases such as stroke, activated microglia phagocytose debris from the primary injury and also secrete molecules that kill nearby normal neurons. By analogy with these diseases, we suggest that microglia activated by primary rod cell death may kill adjacent photoreceptors. Activated microglia may be a missing link in understanding why initial rod cell death in the human diseases RP, L-ORD, and AMD leads to death of the cones that are critical for high acuity daytime vision.

Adult↗
PubMed1999

Photoreceptor rosettes in autosomal dominant retinitis pigmentosa with reduced penetrance.

We performed histopathologic and immunofluorescence studies of autopsy eyes from a 73-year-old woman with autosomal dominant retinitis pigmentosa from a family with reduced penetrance. Light microscopic examination showed extensive photoreceptor loss in most regions. In the temporal midperiphery of the retina, there were patches of remaining photoreceptors, some arranged in rosettes. Electron microscopic examination showed that these rosettes were composed mostly of rods, with a few cone-like inner segments. The malformed photoreceptor elements in the rosette lumens stained positively with anti-rhodopsin, but not with anti-red- and green-cone opsin or anti-blue-cone opsin. To our knowledge, this is the first report of photoreceptor rosettes containing rod photoreceptors in a case of retinitis pigmentosa. Future studies of additional patients will be needed to determine if the rod-abundant rosettes seen in our patient are a characteristic finding of autosomal dominant retinitis pigmentosa with reduced penetrance.

Aged↗
PubMed2005

Developmental abnormalities in the Nuc1 rat retina: a spontaneous mutation that affects neuronal and vascular remodeling and retinal function.

The retina serves as an excellent model in which to study vertebrate CNS development. We have discovered a spontaneous mutation in the Sprague-Dawley rat that results in a novel and unusual ocular phenotype, including retinal abnormalities, that we have named Nuc1. We have previously shown that the Nuc1 mutation appears to suppress programmed cell death in the developing retina. Here we report that maturation of both the retinal neurons and the retinal vessels is abnormal in Nuc1 homozygous rats. The developmental changes in the retinal neurons and vasculature are correlated with regard to degree of abnormality. As Nuc1 homozygotes mature, focal retinal detachment begins at approximately 3 months after birth, and near total traction retinal detachment, associated with pre-retinal fibrosis and neovascularization, is evident by 18 months. Electroretinographic studies at 2.5 months of age indicate that functional retinal degeneration precedes retinal detachment. The functional abnormality is most evident in rods and the inner retina, and is present in homozygous but not heterozygous mutants. Immunocytochemical studies of rod and cone photoreceptors indicate abnormalities in rod, but not cone, photoreceptors in Nuc1 homozygotes, consistent with the electroretinographic findings. In Nuc1 animals, the Muller cells are activated. Although such activation may result from inflammation, Muller cells in Nuc1 may be reacting to a neuronal influence. It appears that the Nuc1 mutation plays a regulatory role in both developing and maturing ocular tissues. The Nuc1 mutation may also serve as an important genetic tool to explore the relationships that may exist among gliosis, normal neuronal development, and normal vascular development and how abnormalities in these associations lead to common retinal diseases.

Amacrine Cells↗
PubMed2004

Inherited retinal degenerations: therapeutic prospects.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerative diseases, characterized by the progressive death of rod and cone photoreceptors. A tremendous genetic heterogeneity is associated with the RP phenotype. Most mutations affect rods selectively and, through an unknown pathway, cause the rod cells to die by apoptosis. Cones, on the other hand, are seldom directly affected by the identified mutations, and yet, in many cases, they degenerate secondarily to rods, which accounts for loss of central vision and complete blindness. Many animal models of RP are available and have led to a better understanding of the disease and to the development of therapeutic strategies aimed at curing the specific genetic disorder (gene therapy), slowing down or even stopping the process of photoreceptor degeneration (growth factors or calcium blockers applications, vitamin supplementation), preserving the cones implicated in the central visual function (identification of endogenous cone viability factors) or even replacing the lost cells (transplantation, use of stem or precursor cells). Still, many obstacles will need to be overcome before most of these strategies can be applied to humans. In this review, we describe the different therapeutic strategies being studied worldwide and report the latest results in this field.

Animals↗
PubMed1996

Damage to the photoreceptor cells of the rabbit retina from 56Fe ions: effect of age at exposure, 1.

Optic and proximate tissues of New Zealand white (NZW) rabbits at ages (approximately 3.5 years) near the middle of their median lifespan (5-7 years) were given 0.5-3.5 Gy of 465 MeV u-1 56Fe ions in the Bragg plateau region of energy deposition at a linear energy transfer (LET infinity) of 220 +/- 31 keV micrometer-1. Dose-dependent losses of retinal photoreceptor cells (rods) occurred until 1-2 years after irradiation, the period of this interim report. Similar cumulative losses of photoreceptor cells were seen during the period 1-2 years post-irradiation for rabbits given comparable exposures when young (6-9 weeks old). Since losses of photoreceptor cells at early times had not been determined previously, the current experiment, which was designed to simulate the responses of mature astronauts, redressed that deficiency.

Age Factors↗
PubMed1994

Visual function testing: clinical correlations.

Visual function tests provide criteria to determine the extent and type of retinal malfunction in patients with retinal disease. This chapter provides an overview of some selected measures of retinal function that are useful as aids in diagnosis of retinal diseases, particularly those that involve the cone and rod photoreceptors.

Adolescent↗
PubMed2004

Identification of extraretinal photoreceptors in the teleost Phoxinus phoxinus.

The existence of cells capable of detecting changes of the photoperiod within the deep brain, the so-called deep brain photoreceptors, was proposed in the early years of the twentieth century. By using immunocytochemistry with antisera against phototransductory proteins on paraffin and vibratome sections, we have localized several positive areas in the brain of the teleost Phoxinus phoxinus. These areas were restricted to two encephalic regions: the epithalamus and the hypothalamus. Immunopositive (rod-opsin- and a-transducin-like) pinealocytes and parapinealocytes, as well as some sparse neurons in the habenula, were seen in the epithalamus. The immunoreaction of the hypothalamus was represented by a-transducin-like positive (magnocellular and parvicellular) neurons of the Nucleus Preopticus, as well as by a-transducin- and arrestin-like positive fibers corresponding to the hypothalamic-hypophyseal tract and a few fibers running towards the basal telencephalon. These findings corroborate the data published on other teleost fish and fully support the hypothesis of the presence of photosensitive cells in the encephalon of lower vertebrates. The labelling with antisera against different components of the phototransductory cascade also strengthens the idea that such cells employ a biochemical mechanism similar to that in the retinal visual photoreceptor cells, rods and cones. Although the function is still unclear, the detection of the photoperiod seems to be the most likely role for these extraretinal photoreceptors.

Animals↗
PubMed2006

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa.

BACKGROUND: The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. METHODS: Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. RESULTS: Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. CONCLUSIONS: Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration.

Animals↗
PubMedDate not supplied

[The cytostructure and morphogenesis of the rod outer segments].

This paper is a review discussing the cytomolecular structure of the rods, retinal photoreceptor cells, whose structural uniformity contributed to the progress in studies of their structure and morphogenesis in the vertebrate eye. Recent studies of protein and phospholipid metabolism in the rod inner segment have been reviewed. The structure of the outer segment connecting cilium is discussed with reference to the TEM and SEM, freeze-fracture, biochemical and immunological studies. The membranes of the rod outer segment undergo continuous renewal. The use of fine biochemical methods permitted to find differences in the structure of the plasma membrane surrounding the rod outer segment and the membrane discs, that fill this segment. Recent hypotheses dealing with morphogenesis of the rod outer segment membrane discs are also discussed. Special attention is paid to actin and myosin, as well as a small transient fraction of galactose-containing rhodopsin.

Animals↗
PubMed1998

[Multi-flash ERG in cone dystrophies and cone-rod dystrophies].

BACKGROUND: Scotopic electroretinograms elicited with a multiple flash procedure were reported to be helpful in diagnosis of macular diseases. To evaluate the contribution of rods and cones to the recovery of light responses as recorded with this technique we performed a triple flash ERG procedure in patients with cone dystrophies and cone-rod dystrophies. MATERIALS AND METHODS: In 8 patients with cone dystrophy and 8 patients with cone-rod dystrophy and also in 18 healthy controls we recorded a standard ERG and the scotopic triple flash ERG with intensities between 0.01 and 0.2 cds/m2. Interflash intervals were adjusted at 140, 280, and 560 ms. Responses of the standard ERG were analysed as well as b-wave amplitudes at the short dark interval (140 ms) and the longer dark interval (280 ms). These responses were compared to responses after a long interflash interval (560 ms). Using a theoretical model parameters of b-wave recovery were determined and compared between the groups. RESULTS: In cone dystrophies responses of the scotopic triple flash ERG and the b-wave recovery parameters were normal whereas in combined dystrophies the triple flash responses were abnormal and the recovery data were pathologic. CONCLUSIONS: Cones did neither contribute to responses obtained with the multiple flash technique nor did they affect b-wave recovery as tested with this technique. Pathologic responses as described earlier with this technique in macular diseases could only be attributed to pathomechanisms globally affecting the rod system, e.g. dysfunction of retinal energy metabolism.

Adolescent↗
PubMed2007

Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study.

Retinal degeneration 10 (rd10) mice are a model of autosomal recessive retinitis pigmentosa (RP), identified by Chang et al. in 2002 (Vision Res. 42:517-525). These mice carry a spontaneous mutation of the rod-phosphodiesterase (PDE) gene, leading to a rod degeneration that starts around P18. Later, cones are also lost. Because photoreceptor degeneration does not overlap with retinal development, and light responses can be recorded for about a month after birth, rd10 mice mimic typical human RP more closely than the well-known rd1 mutants. The aim of this study is to provide a comprehensive analysis of the morphology and function of the rd10 mouse retina during the period of maximum photoreceptor degeneration, thus contributing useful data for exploiting this novel model to study RP. We analyzed the morphology and survival of retinal cells in rd10 mice of various ages with quantitative immunocytochemistry and confocal microscopy; we also studied retinal function with the electroretinogram (ERG), recorded between P18 and P30. We found that photoreceptor death (peaking around P25) is accompanied and followed by dendritic retraction in bipolar and horizontal cells, which eventually undergo secondary degeneration. ERG reveals alterations in the physiology of the inner retina as early as P18 (before any obvious morphological change of inner neurons) and yet consistently with a reduced band amplification by bipolar cells. Thus, changes in the rd10 retina are very similar to what was previously found in rd1 mutants. However, an overall slower decay of retinal structure and function predicts that rd10 mice might become excellent models for rescue approaches.

Animals↗
PubMed2006

Clinical disorders affecting mesopic vision.

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized.

Electroretinography↗
PubMed1994

Rod phototransduction in retinitis pigmentosa: estimation and interpretation of parameters derived from the rod a-wave.

PURPOSE: Relationships between the Lamb and Pugh model of transduction in single rod photoreceptors and the parameters derived from human rod a-waves are examined to evaluate transduction abnormalities in retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). METHODS: ERGs were obtained from 15 patients, 11 with RP and 4 with CRD, and from 15 normal subjects. Rod-only responses were derived from responses to blue (W47B) flashes over a wide range of flash energies by computer-subtracting estimates of the cone contribution. A model of the rod's response was fitted to the a-waves of the rod-only responses as well as to the responses to the blue flashes by estimating three parameters-sensitivity (S), delay (td), and maximum response (RmP3). To assess the limits of the cone contributions to the parameters of the model, ERGs were obtained from two of the patients, two normal subjects, and three additional patients with nondetectable rod responses using white flashes. RESULTS: All patients had significantly decreased values of RmP3, and eight had significantly decreased values of S compared to the control subjects. The values of the parameters estimated from the responses to the blue flashes were reasonably similar to those for the rod-only responses except in patients with nondetectable rod signals. For the white flashes, the estimate of S was considerably larger and the fit of the model noticeably poorer. CONCLUSIONS: The authors reached two conclusions. First, some forms of RP and CRD alter the activation stages of transduction. Transduction appears normal in other patients, despite extensive receptor damage as indicated by markedly reduced RmP3 values. Second, the cone contribution to a blue flash only affects the estimate of the key parameters in patients in whom the rod component is minimal. The cone contribution to a white flash contaminates the fit and the estimate of the parameters in all patients and normal subjects.

Adolescent↗
PubMed1999

Scanning laser densitometry and color perimetry demonstrate reduced photopigment density and sensitivity in two patients with retinal degeneration.

PURPOSE: To test the feasibility of scanning laser densitometry with a modified Rodenstock scanning laser ophthalmoscope (SLO) to measure the rod and cone photopigment distribution in patients with retinal diseases. METHODS: Scanning laser densitometry was performed using a modified Rodenstock scanning laser ophthalmoscope. The distribution of the photopigments was calculated from dark adapted and bleached images taken with the 514 nm laser of the SLO. This wavelength is absorbed by rod and cone photopigments. Discrimination is possible due to their different spatial distribution. Additionally, to measure retinal sensitivity profiles, dark adapted two color static perimetry with a Tübinger manual perimeter was performed along the horizontal meridian with 1 degree spacing. RESULTS: A patient with retinitis pigmentosa had slightly reduced photopigment density within the central +/- 5 degrees but no detectable photopigment for eccentricities beyond 5 degrees. A patient with cone dystrophy had nearly normal pigment density beyond +/- 5 degrees, but considerably reduced photopigment density within the central +/- 5 degrees. Within the central +/- 5 degrees, the patient with retinitis pigmentosa had normal sensitivity for the red stimulus and reduced sensitivity for the green stimulus. There was no measurable function beyond 7 degrees. The patient with cone dystrophy had normal sensitivity for the green stimulus outside the foveal center and reduced sensitivity for the red stimulus at the foveal center. The results of color perimetry for this patient with a central scotoma were probably influenced by eccentric fixation. CONCLUSION: Scanning laser densitometry with a modified Rodenstock SLO is a useful method to assess the human photopigment distribution. Densitometry results were confirmed by dark adapted two color static perimetry. Photopigment distribution and retinal sensitivity profiles can be measured with high spatial resolution. This may help to measure exactly the temporal development of retinal diseases and to test the success of different therapeutic treatments. Both methods have limitations at the present state of development. However, some of these limitations can be overcome by further improving the instruments.

Adult↗
PubMed1994

Development of the rabbit retina. V. The question of 'columnar units'.

A qualitative and quantitative description of the columnar units in the mammalian retina, and a discussion of their ontogeny and putative functions is given. Columnar arrangements of cells exist in the developing retina which can be observed by means of scanning electron microscopy. In the adult retina, each Müller cell ensheaths a columnar group of neuronal cells. Counting the number of cells in radial H/E stained sections at various developmental stages reveals a constant ratio of neuronal cells per Müller cell, independent of the developmental stage (after postnatal day 9), and independent of the retinal topography. Such groups of cells always consist of one Müller cell, 11 rod photoreceptor cells, about 2 bipolar cells, and 1 to 2 amacrine cells. Retinal ganglion cells, cone photoreceptor cells, and horizontal cells are more sparsely distributed in the retina than these units; since they are known to arise earlier in the ontogenesis than other cell types they are considered to exist independently of the columnar units. It is suggested that the units arise by migration of groups of preneurons along a common Müller (precursor) cell; these preneurons and the corresponding Müller cell may be clonally related. In the adult retina, such columns might constitute metabolic and functional units.

Animals↗
PubMedDate not supplied

Residual photosensitivity in mice lacking both rod opsin and cone photoreceptor cyclic nucleotide gated channel 3 alpha subunit.

The mammalian retina contains three classes of photoreceptor. In addition to the rods and cones, a subset of retinal ganglion cells that express the putative sensory photopigment melanopsin are intrinsically photosensitive. Functional and anatomical studies suggest that these inner retinal photoreceptors provide light information for a number of non-image-forming light responses including photoentrainment of the circadian clock and the pupil light reflex. Here, we employ a newly developed mouse model bearing lesions of both rod and cone phototransduction cascades (Rho(-/-) Cnga3(-/-)) to further examine the function of these non-rod non-cone photoreceptors. Calcium imaging confirms the presence of inner retinal photoreceptors in Rho(-/-) Cnga3(-/-) mice. Moreover, these animals retain a pupil light reflex, photoentrainment, and light induction of the immediate early gene c-fos in the suprachiasmatic nuclei, consistent with previous findings that pupillary and circadian responses can employ inner retinal photoreceptors. Rho(-/-) Cnga3(-/-) mice also show a light-dependent increase in the number of FOS-positive cells in both the ganglion cell and (particularly) inner nuclear layers of the retina. The average number of cells affected is several times greater than the number of melanopsin-positive cells in the mouse retina, suggesting functional intercellular connections from these inner retinal photoreceptors within the retina. Finally, however, while we show that wild types exhibit an increase in heart rate upon light exposure, this response is absent in Rho(-/-) Cnga3(-/-) mice. Thus, it seems that non-rod non-cone photoreceptors can drive many, but not all, non-image-forming light responses.

Animals↗