Transplantation of retinal pigment epithelial cells. Scientific advance and social responsibility.
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Animals↗
Biomedical subjects
G A Fishman
Publications and source records attributed to G A Fishman.
Mechanisms of rod-cone interaction: evidence from congenital stationary nightblindness.
The dark-adapted rod system can elevate cone-mediated thresholds for flicker detection as well as thresholds for the detection of hue. We examined these two types of rod-cone interactions in two individuals with congenital stationary nightblindness (CSNB), a retinal disorder in which rod outer segment function is intact, but in which a defect occurs in the transmission of rod signals within the retina. The two types of rod-cone interaction were differentially affected by the retinal pathology; the rod-cone flicker interaction was normal, but the rod-cone hue interaction was absent. These results provide evidence that, despite similarities in the adaptational properties of these two types of rod-cone interaction, they are mediated by different visual mechanisms.
Adolescent↗
Rod and cone dysfunction in carriers of X-linked retinitis pigmentosa.
Carriers of X-linked retinitis pigmentosa were studied using electroretinographic and psychophysical procedures. Under both dark- and light-adapted (cone-isolated) conditions, electroretinogram (ERG) a-waves of carriers were reduced in amplitude but normal in implicit time, whereas b-waves were reduced in amplitude and delayed in implicit time. Reductions in b-wave amplitudes of the carriers as a group were equivalent for the rod and cone systems. Luminance-response functions for both dark-adapted and cone-isolated b-waves were fit by the Naka-Rushton equation and demonstrated a selective reduction of Rmax; the semi-saturation constant (K) and the slope parameter (n) were normal. Electroretinograms recorded using the brightest stimulus flashes were most effective at distinguishing carriers from normals. Absolute thresholds of the carriers were elevated significantly across the central 40 degrees of the visual field. As a group, the threshold elevations of the carriers were approximately equal for the rod and cone systems.
Adult↗
Psychophysical and electroretinographic findings in X-linked juvenile retinoschisis.
We compared psychophysical and electroretinographic test results of four patients with X-linked juvenile retinoschisis who had clinically apparent lesions isolated to the foveal area. The b-wave of the flash electroretinogram was selectively reduced, while the a-wave was within the normal range. Oscillatory potentials generated by either the rod or cone systems were markedly reduced. Absolute thresholds outside the fovea were either normal or only moderately elevated, indicating that the sensory neural pathways were, by and large, operating with limited dysfunction. Therefore, the oscillatory potentials do not directly reflect, to any appreciable extent, the function of bipolar or ganglion cells. Finally, a sequence of pathologic events is proposed for X-linked juvenile retinoschisis that initiates with Müller cell dysfunction.
Adolescent↗
Electroretinographic findings in sickle cell retinopathy.
We obtained electroretinograms (ERGs) from normal subjects and from patients with sickle cell disease. The ERG components (a-wave, b-wave, and oscillatory potentials) obtained from normal subjects and patients without peripheral retinal neovascularization did not differ in either amplitude or implicit time. However, ERG components obtained from patients with peripheral retinal neovascularization were reduced in amplitude compared with those obtained from normal subjects or patients without neovascularization. The reduced a-wave, b-wave, and oscillatory potential amplitudes may have been due to photoreceptor dysfunction secondary to choroidal ischemia or possibly increased oxygen demands by the inner retina. Ischemia of the inner retina may also have contributed to the altered b-wave and oscillatory potentials. These results suggest that ERG provides a means of assessing the consequence of peripheral retinal ischemia to retinal cell function and could be of value in monitoring patients with sickle cell disease for the development of clinically significant peripheral retinal neovascularization.
Anemia, Sickle Cell↗
Rod and cone system contributions to oscillatory potentials: an explanation for the conditioning flash effect.
The oscillatory potentials (OPs) of the human electroretinogram (ERG) are smaller in response to the initial flash of a series than to subsequent flashes. To investigate a possible rod system contribution to this "conditioning flash effect," we have examined OPs in normals and rod monochromats. The OPs recorded from rod monochromats were similar to those recorded from normals under test conditions that selectively stimulate rods. However, under conditions that in normals stimulate both rods and cones and that result in maximal amplitude of the OPs, the rod monochromats exhibit markedly reduced OPs. This finding suggests that the initial (conditioning) flash operates by adapting the rod system contribution to the OPs, so that the OPs in response to subsequent flashes result primarily from the cone system. In agreement with this hypothesis, the conditioning flash effect did not occur when flashes were presented against a background which eliminated the rod system response nor during the cone plateau phase of dark adaptation.
Color Vision Defects↗
Macular pigment and reduced foveal short-wavelength sensitivity in retinitis pigmentosa.
Some patients with retinitis pigmentosa (RP) show a reduced foveal short-wavelength sensitivity that cannot be attributed to a reduction in the sensitivity of the short-wavelength cone system. To determine whether an increased amount of macular pigment (xanthophyll) might account for this finding, we derived estimates of the two-way optical density of the macular pigment of five such RP patients as well as of five normals. The spectral reflectance of the foveal region of each subject was obtained from digitized images of the bleached fundus provided by a television-based reflectometer. The density spectra of the macular pigment, melanin, and oxygenated hemoglobin were fit by a least-squares procedure to the log of the ratio of parafoveal to foveal spectral reflectance in order to obtain a quantitative estimate of the contribution of each of these ocular pigments to foveal short-wavelength reflectance. By this analysis, the two-way densities of the macular pigment, melanin, and oxyhemoglobin of the RP patients were not significantly different from those of the normals. Therefore, the reduced foveal short-wavelength sensitivity of these patients was not due to an increased amount of macular pigment, but may result instead from morphological abnormalities in the foveal cones such that a normal amount of macular pigment screens the cones more effectively.
Adult↗
Abnormal plasma levels of polyunsaturated fatty acid in autosomal dominant retinitis pigmentosa.
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Docosahexaenoic Acids↗
Interferon-gamma production and HLA-DR expression in patients with retinitis pigmentosa.
Other investigators have reported deficient production of interferon-gamma (IFN-gamma) and reduced expression of class II major histocompatibility (HLA-DR) antigens on monocytes from patients with retinitis pigmentosa (RP). Our previous investigation did not demonstrate deficient IFN-gamma production by lymphocytes from patients with RP. We have extended our previous study by determining the frequency of HLA-DR-positive monocytes in the peripheral blood of well-defined groups of RP patients and by including a larger sample size of patients and subdividing the autosomal dominant and recessive subpopulations. Our present results confirm and extend our previous finding that lymphocytes from patients with RP are not deficient in the production of IFN-gamma as assessed with a commercially available radioimmunoassay test kit. In addition, using two-color immunofluorescence staining and flow cytometry, we also demonstrated normal expression of HLA-DR antigens on monocytes from these patients. In both this and our previous study, using techniques employed in our laboratory, we have been unable to detect significant cell-mediated immune abnormalities in a large and well-characterized group of RP patients.
Adult↗
Visual acuity loss in patients with Stargardt's macular dystrophy.
Ninety-five patients with Stargardt's macular dystrophy were appraised for visual loss with age by both life-table analyses and cross-sectional procedures. The probability of maintaining a visual acuity of 20/40 or better in at least one eye was 52% by age 19, 32% by age 29, and 22% by age 39. In the population studied, once a patient's visual acuity dropped below 20/40, it tended to decrease rapidly and stabilize at 20/200. Fluorescein angiograms obtained on 64 of the 95 patients showed a "dark choroid" in 55 (85.9%). This finding, therefore was present in the majority of the patients, although its absence does not rule out Stargardt's macular dystrophy.
Actuarial Analysis↗
Antiphospholipid antibodies associated with retinal vascular disease.
Two patients with retinal vascular disease also had antiphospholipid antibodies, defined by the presence of the circulating lupus anticoagulant (LAC), anticardiolipin antibodies, or both. One had retinal arterial occlusions and the other had a nonischemic central retinal vein occlusion. The association of thrombotic vascular disease, including both retinal and cerebral vessels, with the presence of these antibodies should be investigated in otherwise normal individuals or in patients presenting with a lupuslike syndrome and retinal vascular occlusive disease. Low-dose aspirin administration could be of therapeutic value in managing thrombotic events in this group of patients.
Adult↗
Magnetic resonance imaging of central nervous system defects in Usher's syndrome.
With the use of magnetic resonance imaging, seven patients with type II Usher's syndrome were evaluated for CNS defects. The goals of this study were to confirm the presence of CNS defects previously detected by computed tomography (CT) scans in patients with Usher's syndrome while seeking additional anatomic defects in the posterior fossa employing a potentially more sensitive procedure using magnetic resonance imaging. Findings of CNS lesions in both the midbrain (high-signal-intensity lesions) and the cerebellum (vermian atrophy) necessitate further characterization of these defects in terms of their progressive nature and clinical significance for patients with Usher's syndrome.
Adult↗
Abnormal foveal spectral sensitivity in retinitis pigmentosa.
The authors measured dark-adapted foveal spectral sensitivity functions in 30 patients with retinitis pigmentosa or Usher's syndrome, whose Snellen visual acuities were 20/30 or better. An analysis of variance of the spectral sensitivity functions (normalized at 575 nm) indicated a significant reduction in the patients' relative sensitivity at 450 and 475 nm compared with a group of 15 age-similar normal observers, while the patients' relative sensitivity at middle and long wavelengths was normal. A significant negative correlation between the patients' normalized sensitivity at 450 nm and their non-normalized sensitivity at 575 nm indicated that patients with a normal absolute sensitivity at 575 nm had the greatest reduction in relative sensitivity at 450 nm. The characteristics of the short-wavelength sensitivity loss suggest that it results from an increase in the effective optical density of the yellow macular pigment, rather than from a decreased sensitivity of a specific cone mechanism or an increased lens absorption.
Adult↗
Foveal cone pigment density difference and reflectance in retinitis pigmentosa.
Cone pigment density difference refers to a change in light absorption by cones before and after bleaching of their visual pigments. With a television ophthalmoscope image processor, we measured the foveal cone pigment density difference in patients with retinitis pigmentosa (RP), good central vision, and no clinically apparent foveal lesion. Foveal reflectance was obtained at 12 different wavelengths of illumination. Compared with similar-aged normal subjects, most patients with dominantly inherited RP had normal or minimally reduced cone pigment density difference within the central fovea, relatively lower than normal density difference at the foveal margin, and increased foveal reflectance. Compared with these normal subjects, patients with recessively inherited RP had significantly reduced cone pigment density difference within the central fovea, relatively more normal density difference at the foveal margin, and normal foveal reflectance.
Absorption↗
Abnormal sperm and photoreceptor axonemes in Usher's syndrome.
Axonemes are organelles that are composed of microtubule doublets and singlets with a complex assembly of associated proteins. This study was designed to investigate the possibility that an abnormal axoneme is involved in the pathogenesis of Usher's syndrome. A masked structural and functional analysis of sperm was performed on samples from ten patients with Usher's syndrome and 33 controls, including duplicate samples from six patients and three controls. In the functional analyses, there was a significant decrease in patient sperm motility and velocity. Structurally, there was a significant increase in tail abnormalities at both the light and electron microscopic levels. Ejaculate volume and sperm concentration were normal in the patient population. The presence of abnormal axonemes was also confirmed in remnant photoreceptors of a whole eye donation from a patient with Usher's syndrome. The data suggest that defective connecting cilia axonemes may be involved in the irreversible, progressive loss of photoreceptors in Usher's syndrome.
Adult↗
Dark-adapted foveal thresholds and visual acuity in retinitis pigmentosa.
To determine the relationship of foveal absolute thresholds to visual acuity in retinitis pigmentosa, we measured thresholds in 40 patients with various forms of retinitis pigmentosa (including Usher's syndrome) whose Snellen visual acuities were 20/30 or better. At all visual acuity levels, the patients' foveal thresholds were significantly higher than those of 20 similarly aged normal observers; threshold elevations tended to be greater for a 500-nm than for a 655-nm test flash. Foveal cone spatial summation functions were normal (test flash diameter range, 7' to 1.7 degrees), indicating that the patients' threshold elevations did not result from altered summation properties. A significant correlation between foveal cone thresholds and the midpoints of the patients' Rayleigh matches demonstrated that the threshold elevations resulted in part from a decreased cone optical density.
Adolescent↗
Blood-retinal barrier function in patients with cone or cone-rod dystrophy.
We assessed blood-retinal barrier function by vitreous fluorophotometry in 24 patients with either cone or cone-rod dystrophy who were segregated into three subgroups. Compared with a normal population, the patients demonstrated increased vitreous fluorescence (breakdown of the blood-retinal barrier) that positively correlated with peripheral pigmentary changes and an appreciable reduction in electroretinographic scotopic b-wave amplitude. A unique subgroup of three women with supernormal electroretinographic scotopic b-wave amplitudes to a high-intensity stimulus had an abnormal increase in permeability of the blood-retinal barrier even without peripheral pigmentary fundus changes.
Adolescent↗
X-linked recessive retinitis pigmentosa. Clinical characteristics of carriers.
We evaluated 46 carriers of X-linked recessive retinitis pigmentosa for the prevalence of fundus changes, refractive errors, central visual impairment, and electroretinographic abnormalities. Of the 46 carriers, 40 (87%) could be identified by characteristic fundus changes and 37 (86%) of 43 by reductions in electroretinographic amplitude. Interestingly, 36 carriers (78%) had a refractive cylindrical correction of +1.50 diopters (D) or greater in at least one eye, while 25 (54%) had a best corrected visual acuity of 20/30 or less in at least one eye. Fundus examination coupled with an electroretinographic recording was diagnostic of the carrier state in virtually all 46 patients. The presence of a refractive cylinder of +1.50 D or greater should appreciably increase the index of suspicion when assessing the possibility of the carrier state in X-linked retinitis pigmentosa.
Adolescent↗