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Results for “Retinal Rod Photoreceptor Cells”

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PubMed1994

Cone cells fail to develop normally in transgenic mice showing ablation of rod photoreceptor cells.

Transgenic mice were derived containing the cytotoxic dt-alpha gene driven by opsin promoter sequences. Mice expressing this construct showed progressive degeneration of rod photoreceptor cells commencing at birth, with obvious depletion of such cells by postnatal day 7. Ablation of rod photoreceptor cells in the transgenic retina was accompanied by the failure of developing cone cells to elaborate outer segments, although all other aspects of cone cell cytodifferentiation appeared normal. The results suggest that the 1.0-kb opsin promoter segment contains rod cell type specificity and that cone cells require maturation of rod cells to complete the late stages of their terminal differentiation and for their maintenance and cellular integrity.

Animals↗
PubMed2004

Connexin 36 in photoreceptor cells: studies on transgenic rod-less and cone-less mouse retinas.

PURPOSE: Rod-cone gap junctions permit transmittal of rod visual information to the cone pathway. A recent report has shown that this transfer does not occur in mice in which the gap junction protein connexin 36 is knocked out indicating that rod-cone gap junctions are assembled from this protein. It remains unresolved, however, whether rods, cones or both express connexin 36. We have tried to address this question with the use of transgenic rod-less and cone-less mice. METHODS: Deletion of Nrl, a transcription factor, results in a complete loss of rods with a concomitant increase in S-cones. We used this as the rod-less (cone-only) model. Cone-less (rod-only) retinas were from mice expressing an attenuated diphtheria toxin gene under the control of a promoter selective for cones. Nearly all long wavelength cones and 95% of short wavelength cones are missing in this model. Fixed retinal sections from these two models and age matched controls were used to detect connexin 36 gap junctions by immunofluorescence. RESULTS: Punctate immunofluorescence, indicating the presence of gap junctions, was observed in the inner and outer plexiform layers of both wild type and cone-less and rod-less retinas. Our assumption was that immunofluorescence due to photoreceptor gap junctions would be observed in the outer plexiform layer. In all the animals, most of the immunofluorescence was in the inner plexiform layer, with only a marginal reaction in the outer plexiform layer. In cone-only (rod-less) retina, immunofluorescence in the outer plexiform layer increased by more than 20 fold compared to wild type. In rod-only (cone-less) retina, the outer plexiform layer showed about a 30% decrease in immunofluorescence. In both rod-less and cone-less retinas, immunofluorescence in the inner plexiform layer was higher than in the wild type by 25-50%. CONCLUSIONS: Cones constitute only about 3% of photoreceptors in the wild type retina while they make up 100% of the photoreceptors in cone-only retina. This increase in their numbers coincided with a 20 fold increase in immunofluorescence in the outer plexiform layer, strongly suggesting that cones express connexin 36. Conversely, when the cone numbers went down from 3% to near zero in cone-less retina, immunofluorescence decreased by about 30% in the outer plexiform layer, suggesting again that cones express the connexin and that they contribute to its presence disproportionately more than their numbers indicate. The results from both rod-less and cone-less animals are strongly indicative of cones expressing connexin 36, but are not sufficient to conclude whether rods express the protein. An unexpected observation from our experiments is that immunofluorescence increases slightly in the inner plexiform layer in both rod-less and cone-less retina for reasons that need further investigation.

Animals↗
PubMed2001

Rod and cone a-waves in three cases of Bietti crystalline chorioretinal dystrophy.

PURPOSE: To estimate retinal function in Bietti crystalline chorioretinal dystrophy using the electroretinogram. METHODS: In this observational case series, the scotopic and photopic electroretinograms in three Japanese female patients (case 1, 55 years old; case 2, 56 years old; case 3, 47 years old) who showed bilateral crystalline retinal deposits but no corneal deposits were recorded. The rod and cone a-waves were analyzed by using the method described by Hood and Birch (1995, 1997). The parameters Rm(p3) (maximum a-wave amplitude) and S (sensitivity) were calculated. RESULTS: In case 1, the rod Rm(p3) was decreased in both eyes. The rod S in the right eye was within the normal range, but that in the left eye was significantly reduced. Although the cone Rm(p3) was decreased, the cone S was within the normal range. In case 2, the rod and cone Rm(p3) was reduced, but the rod and cone S was within the normal range in both eyes. In case 3, the rod and cone Rm(p3) and S were within the normal range. CONCLUSIONS: Electroretinograms illustrated different disease stages, however, no eye with normal Rm(p3) and decreased S was found in rods and cones. In the early stages of this disease, decreased numbers of photoreceptors and/or outer segment shortening may be present while phototransduction remains normal. As the damage to the retina progresses, phototransduction becomes severely affected. Because reduced cone S was not observed in our cases, cones may be less involved than rods in this disease.

Crystallization↗
PubMedDate not supplied

Visual pigment composition in zebrafish: Evidence for a rhodopsin-porphyropsin interchange system.

Numerous reports have concluded that zebrafish (Danio rerio) possesses A1-based visual pigments in their rod and cone photoreceptors. In the present study, we investigated the possibility that zebrafish have a paired visual pigment system. We measured the spectral absorption characteristics of photoreceptors from zebrafish maintained in different temperature regimes and those treated with exogenous thyroid hormone using CCD-based microspectrophotometry. Rods from fish housed at 15 degrees C and 28 degrees C were not significantly different, having lambda max values of 503 +/- 5 nm (n = 106) and 504 +/- 6 nm (n = 88), respectively. Thyroid hormone treatment (held at 28 degrees C), however, significantly shifted the lambda max of rods from 503 +/- 5 nm (n = 194) to 527 +/- 8 nm (n = 212). Cone photoreceptors in fish housed at 28 degrees C (without thyroid hormone treatment) had lambda max values of 361 +/- 3 nm (n = 2) for ultraviolet-, 411 +/- 5 nm (n = 18) for short-, 482 +/- 6 nm (n = 9) for medium-, and 565 +/- 10 nm (n = 14) for long-wavelength sensitive cones. Thyroid hormone treatment of fish held at 28 degrees C significantly shifted the lambda max of long-wavelength sensitive cones to 613 +/- 11 nm (n = 20), substantially beyond that of the lambda max of the longest possible A1-based visual pigment (approximately 580 nm). Thyroid hormone treatment produced smaller shifts of lambda max in other cone types and increased the half-band width. All shifts in photoreceptor lambda max values resulting from thyroid hormone treatment matched predictions for an A1- to A2-based visual pigment system. We therefore conclude that zebrafish possess a rhodopsin-porphyropsin interchange system that functions to spectrally tune rod and cone photoreceptors. We believe that these observations should be carefully considered during analysis of zebrafish spectral sensitivity.

Animals↗
PubMed1999

Structural and functional rescue of murine rod photoreceptors by human rhodopsin transgene.

Mice carrying a targeted disruption of the rhodopsin gene develop a severe degenerative retinopathy, failing to elaborate rod photoreceptor outer segments (ROS), having no recordable rod electroretinogram (ERG) and losing all of their rod cells over a period of approximately 12 weeks. Murine and human rhodopsins differ in their amino acid sequences. Whether, or to what extent, such variability might influence the ability of human rhodopsin to serve as an adequate structural and functional substitute for the endogenous protein in mouse rod cells bears direct relevance to exploiting the full utility of Rho-/-animals as a model of degenerative retinal disease in man. We crossed Rho-/-mice with mice expressing a wild-type human rhodopsin transgene at levels approximating to those of the endogenous protein. Immunohistological examination of retinal selections from such animals demonstrated ROS of normal number and length and temporal expression of rhodopsin similar to that observed in wild-type animals; that is, immunoreactivity to an anti-rhodopsin antibody became clearly evident by day 3 post-partum. Whereas Rho-/-mice never display a rod ERG response, and even lose cone responses by 12 weeks of age, rescued mice showed 75% normal maximum amplitudes and had ERG b-wave thresholds (based on a 50 microV criterion) within 0.1 log unit of normal wild-type at 20 weeks, and cone amplitudes remained normal at this age. These data demonstrate very substantial structural and functional rescue of the rod photoreceptors of Rho-/-mice and long-term preservation by the human rhodopsin transgene.

Animals↗
PubMed1999

Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors.

Circadian rhythms of mammals are entrained by light to follow the daily solar cycle (photoentrainment). To determine whether retinal rods and cones are required for this response, the effects of light on the regulation of circadian wheel-running behavior were examined in mice lacking these photoreceptors. Mice without cones (cl) or without both rods and cones (rdta/cl) showed unattenuated phase-shifting responses to light. Removal of the eyes abolishes this behavior. Thus, neither rods nor cones are required for photoentrainment, and the murine eye contains additional photoreceptors that regulate the circadian clock.

Animals↗
PubMed2005

Enhanced cone dysfunction in rats homozygous for the P23H rhodopsin mutation.

The heterozygous P23H transgenic rat is a model of autosomal dominant retinitis pigmentosa, in which a mutation in the rhodopsin gene leads to a rapid loss of rods and a more protracted loss of cones. It has been suggested that rods play an essential role in preserving cones. We tested this hypothesis by examining whether higher levels of dysfunctional rhodopsin in rats homozygous for the P23H mutation would result in exacerbated cone dysfunction when compared with heterozygous P23H rats. Electroretinogram (ERG) responses were recorded from P21 to P250 in Sprague-Dawley (SD) and homozygous P23H rats. Both scotopic and photopic intensity response ERGs were severely depressed already at P21 when compared with age-matched SD rats. Furthermore, flicker amplitudes and critical fusion frequencies were also lower in P23H compared with SD rats at P21. Scotopic and photopic intensity responses as well as flicker amplitude and critical fusion frequencies declined rapidly up to P60, reaching a steady state that was maintained up to P200. We conclude that in rats homozygous for P23H rhodopsin mutations, the severe loss of rod function already seen by P21 is accompanied by substantial cone functional loss at that age. While rod-related responses are more severely affected than cone-related responses at all ages, their actual rate of decline with age is surprisingly similar. Both undergo a biphasic temporal pattern of decline: very rapid (P21-P60) followed by very slow (P60-P200) deterioration in response parameters, implying a tight link between rod and cone functional deterioration.

Aging↗
PubMed2004

The visual cycle of the cone photoreceptors of the retina.

The photoreceptors of the eye's retina consist of rods and cones; rods serve vision in dim light, whereas cones serve high-resolution color vision in daylight. The first event in vision is the light-initiated isomerization of 11-cis-retinal, which is attached to rod or cone opsin, to all-trans-retinal. The regeneration of 11-cis-retinal comprises the well-known visual cycle in rods. By using cone-dominant retinas from chickens and ground squirrels, a visual cycle has been discovered in cones that differs radically from that in rods, mainly in the mechanism of isomerization of all-trans-retinol to 11-cis-retinol, and the latter's oxidation to 11-cis-retinal.

Animals↗
PubMedDate not supplied

Rod-driven focal macular electroretinogram.

PURPOSE: To determine the stimulus conditions required to elicit rod-driven, focal macular electroretinograms (rod FMERGs). METHODS: A blue (lambda(max)=470 nm) stimulus, 5 degrees in size, was imaged at a luminance of 1.5 cd/m(2) on different regions of the human retina. Electroretinograms (ERGs) elicited by this stimulus were recorded from the light- and dark-adapted retina of four subjects without any ophthalmological abnormalities. A subject with cone dystrophy was also tested by this method. RESULTS: Stimulus luminance <==1.5 cd/m(2) did not elicit a response when it was imaged on the optic disc, but higher intensities elicited a small b-wave from stray light. When this stimulus was imaged on the macular area or the 15 degrees temporal retina, an ERG was elicited that had the shape of the full-field scotopic ERG. This stimulus with a luminance of 1.5 cd/m(2) did not elicit a response from stimulation of the macular area of a light-adapted retina but elicited a slow-rising positive b-wave after 30 minutes of dark adaptation. In a subject with cone dystrophy, focal rod response was elicited from the macula, despite no response under photopic conditions. CONCLUSION: We conclude that this stimulus will elicit a response that is derived exclusively from rods and is a focal response with no contribution from stray light.

Adult↗
PubMed1993

Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina.

PURPOSE: Because previous studies suggested degeneration and loss of photoreceptors in aged human retina, the spatial density of cones and rods subserving the central 43 degrees of vision as a function of age was determined. METHODS: Cones and rods were counted in 27 whole mounted retinas from donors aged 27 to 90 years with macroscopically normal fundi. Photoreceptor topography was analyzed with new graphic and statistical techniques. RESULTS: Changes in cone density throughout this age span showed no consistent relationship to age or retinal location, and the total number of foveal cones was remarkably stable. In contrast, rod density decreased by 30%, beginning inferior to the fovea in midlife and culminating in an annulus of deepest loss at 0.5 to 3 mm eccentricity by the ninth decade. Space vacated by dying rods was filled in by larger rod inner segments, resulting in a similar rod coverage at all ages. At the temporal equator, cone density declined by 23%, but rods were stable throughout adulthood. CONCLUSIONS: The stability of both rod coverage and rhodopsin content despite decreasing cell number suggests plasticity of the adult rod system and that age-related declines in scotopic sensitivity may be due to postreceptoral factors. There is no evidence for the massive loss of foveal cones required to explain even modest decrements in acuity, consistent with evidence that visual deficits at high photopic levels may be largely due to optical factors. Why the rods of central retina, which share a common support system and light exposure with the neighboring cones, are preferentially vulnerable to aging remains to be determined.

Adolescent↗
PubMed2000

Effects of dopamine depletion on visual sensitivity of zebrafish.

The visual sensitivity of zebrafish in which the retinal dopaminergic interplexiform cells (DA-IPCs) were destroyed by 6-hydroxydopamine was measured behaviorally. During the first 6-8 min of dark adaptation, visual thresholds of DA-IPC-depleted animals were similar to those of control animals. Thereafter, their visual thresholds were elevated so that by 14-18 min of dark adaptation, they were 2-3 log units above those of control animals. In DA-IPC-depleted animals, the electroretinogram was normal in terms of light sensitivity and waveform, but the light threshold for eliciting a ganglion cell discharge was raised by 1.8 log units as compared with control animals. No obvious rod system function was detected in DA-IPC-depleted animals as measured behaviorally. Partial rescue of the behavioral visual sensitivity loss in DA-IPC-depleted animals occurred when dopamine or a long-acting dopamine agonist (2-amino-6, 7-dihydroxy-1, 2, 3, 4-tetrahydronaphthalene hydrobromide) were injected intraocularly. Our data suggest that the principal visual defect shown by DA-IPC-depleted animals is attributable to effects occurring in the inner retina, mainly on rod signals. We also show that dopamine is involved in mediating the effect of the circadian clock on visual sensitivity.

Animals↗
PubMed2000

X-Ray diffraction analysis of three-dimensional crystals of bovine rhodopsin obtained from mixed micelles.

Rhodopsin, a prototypic G protein-coupled receptor responsible for absorption of photons in retinal rod photoreceptor cells, was selectively extracted from bovine rod outer segment membranes, employing mixed micelles of nonyl beta-d-glucoside and heptanetriol. Highly purified rhodopsin was crystallized from solutions containing varying amounts of detergent and amphiphile. The crystals contained ground state rhodopsin molecules as judged by their red color and the linear dichroism originating from the 11-cis-retinal chromophore. However, when exposed to visible light, even at 4 degrees C, rhodopsin was bleached and the crystals decomposed. Reflections in the diffraction pattern were observed out to 3.5-A resolution at 100 K for the most ordered crystals. Diffraction data have been processed to 3.85-A resolution. The symmetry of the diffraction pattern and the systematic absences indicate that the crystals have tetragonal symmetry, space group P4(1)22 or P4(3)22, a = b = 96.51 A, c = 148.55 A. A value of 4.12 A(3)/Da for V(M) was obtained for one monomer in the asymmetric unit (eight molecules per unit cell). Our study is the first characterization of a three-dimensional crystal of a G protein-coupled receptor and may be valuable for future structural studies on related receptors of this important superfamily.

Animals↗
PubMed2002

Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal dystrophy.

Mutations in the photoreceptor transcription factor cone-rod homeobox (CRX) have been identified in patients with several forms of retinal degenerative disease. To investigate the mechanisms by which these mutations cause photoreceptor degeneration, CRX constructs representing eleven known mutations, as well as a set of C-terminal deletions, were generated and tested for their ability to activate a rhodopsin-luciferase reporter in a transient cell transfection assay. To further define functional domains, several Gal4dbd-Crx fusions were similarly tested using a Gal4 response element containing heterologous promoter. This analysis demonstrated that the C-terminal region, between amino acids 200 and 284, is essential for CRX-mediated transcriptional activation. Consistent with this, four mutants carrying C-terminal truncations demonstrated significantly reduced transcriptional activation. Confirming the importance of the homeodomain (HD), four of the five mutants carrying HD missense mutations displayed altered transactivating activity, either decreased (three) or increased (one). In vitro protein-DNA binding assays (EMSAs) with CRX-HD peptides representing the three HD mutants with decreased transactivating activity, indicated that the alteration was due to reduced, but not abolished, DNA binding to CRX targets. Taken together, these results support the hypothesis that CRX mutations involved in human photoreceptor degeneration act by impairing CRX-mediated transcriptional regulation of the photoreceptor genes. However, a clear relationship between the magnitude of biochemical abnormality and degree of disease severity was not observed, suggesting that other genetic and environmental modifiers may also contribute to the disease phenotype.

Amino Acid Sequence↗
PubMed1998

Histopathologic and immunohistochemical study of dominant cone degeneration.

PURPOSE: To report the histopathologic and immunohistochemical findings in autosomal dominant cone degeneration. METHODS: The autopsy eyes of a 75-year-old man with autosomal dominant cone degeneration were studied with both light and electron microscopy. In addition, immunofluorescent studies using antibodies to cone opsins and cone alpha transducin were performed. RESULTS: Histopathologic examination of the fovea disclosed loss of photoreceptors and attenuated retinal pigment epithelium. Reduced numbers of cones could be seen in the parafovea, and only occasional cones were visible in the periphery; rods were preserved in the periphery. CONCLUSION: The histopathologic and immunohistochemical findings in this case of dominantly inherited cone degeneration correlate well with the loss of cone function and preservation of normal or nearly normal rod function upon clinical examination. This condition affects red, green, and blue cones.

Aged↗
PubMed2000

Characterization of rhodopsin mis-sorting and constitutive activation in a transgenic rat model of retinitis pigmentosa.

PURPOSE: To determine the extent to which rhodopsin mis-sorting and constitutive activation of the phototransduction cascade contribute to retinal degeneration in a transgenic rat model of retinitis pigmentosa. METHODS: Retinas from transgenic rats expressing truncated rhodopsin (Ser334ter) were examined by light and electron microscopic immunocytochemistry at several time points. Retinal degeneration in transgenic rats raised in darkness was evaluated by quantification of outer nuclear layer thickness and by electroretinography. RESULTS: Mutant rhodopsin was found at inappropriately high levels in the plasma membrane and cytoplasm of Ser334ter rat photoreceptors. When the cell death rate was high this mis-sorting was severe, but mis-sorting attenuated greatly at later stages of degeneration, as the cell death rate decreased. The distributions of two other outer segment proteins (the cGMP-gated channel and peripherin) were examined and found to be sorted normally within the photoreceptors of these rats. Raising Ser334ter transgenic rats in darkness resulted in minimal rescue from retinal degeneration. CONCLUSIONS: Because dark rearing Ser334ter rats results in little rescue, it is concluded that constitutive activation of the phototransduction cascade does not contribute significantly to photoreceptor cell death in this rat model. The nature of the rhodopsin sorting defect and the correlation between the severity of mis-sorting and rate of cell death indicate that truncated rhodopsin may cause apoptosis by interfering with normal cellular machinery in the post-Golgi transport pathway or in the plasma membrane.

Animals↗
PubMed2002

Differential expression of cone opsin mRNA levels following experimental retinal detachment and reattachment.

PURPOSE: To identify changes in S- and M-sensitive cone opsin gene expression following retinal detachment (RD) and reattachment. METHODS: Cat retinas were detached for 1, 3, 7, or 28 days, or reattached after 1 h, 1 day, or 3 days of RD and fixed in 4% paraformaldehyde. Pieces of mid-peripheral retina were removed from the same region of each detached, normal (attached), and reattached retina and embedded in paraffin. Paraffin sections (8 mm) were processed for in situ hybridization using S- or M-cone opsins, rod opsin, or phosducin riboprobes in vitro transcribed from cat partial cDNAs. Labeled cells were counted to obtain the number of labeled cells/mm retina. RESULTS: The number of cells labeled with the anti-sense cone opsin riboprobes, and the intensity of this label, decreased after RD. The number of cones labeled with the anti-sense S-opsin riboprobe decreased to 42% of normal at 3 days of RD. The number of M-opsin mRNA-positive cones decreased to 4% of normal at 3 days of RD. The number of cells positive for M-opsin or S-opsin mRNA recovered to near normal levels after reattachment. Phosducin and rod opsin mRNA labeling was near normal in surviving rod photoreceptors after RD. CONCLUSIONS: Cones and rods behave differently after detachment. There are significant obstacles to overcome in order to study the responses of cones after RD because surviving cells no longer label with antibodies used as cone markers in normal retina. The results of this study show that: (1) After RD, surviving cones decrease their expression of opsin mRNA while rods do not; (2) Upon reattachment of the retina, the cones once again begin to express their opsins; (3) Most cones survive short-term detachments; and (4) Defects in cone-based vision after reattachment may not be based mainly on the loss of cones but due to other changes in these cells, for example, reduced phototransduction and/or changes in synaptic connectivity to second order neurons.

Animals↗