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M S Silverman

Publications and source records attributed to M S Silverman.

At least 19 recordsLinked to original sources
PubMed1995

Cochlear and retinal degeneration in the tubby mouse.

A number of autosomal recessive syndromes feature both sensorineural hearing loss and retinal degeneration. The mouse mutant tubby also combines hearing loss with progressive retinal degeneration, and thus may constitute a useful model of one form of human sensorineural deafness/retinal dystrophic syndrome. It has not been directly demonstrated that the hearing loss in this mouse involves the cochlea, however. We have examined the cochleas of adult tubby mice using light microscopy. The tubby cochlea shows pronounced degeneration of the organ of Corti and loss of afferent neurons in the base, with relative sparing of the apex. Our findings support the tubby mouse as a model of human sensorineural deafness/retinal dystrophic syndrome. Possible human counterparts include Usher's, Alstrom's, and Bardet-Biedl syndromes.

Animals↗
PubMed1995

Retinal pigment epithelial repopulation in monkeys after submacular surgery.

BACKGROUND: Transplantation of retinal pigment epithelium may be a treatment for retinal diseases, such as age-related macular degeneration and hereditary macular degeneration. Before transplantation studies are undertaken, questions concerning repopulation of retinal pigment epithelial cells in situ and photoreceptor repair after submacular surgery need to be addressed. METHODS: We removed the retinal pigment epithelium from Bruch's membrane in the macaque monkey in the macula and outside the vascular arcades. This model allowed the study of in situ retinal pigment epithelium regrowth and photoreceptor repair for 9 months following débridement. RESULTS: Fluorescein angiography revealed a window defect in the area of denuded retinal pigment epithelium. Histologic studies revealed repopulated nonpigmented retinal pigment epithelial cells in the denuded areas in both the early and late periods. At 9 months, the repopulated retinal pigment epithelium was associated with repaired, normal-appearing photoreceptor outer segments. Retinal pigment epithelium regrowth was observed only if Bruch's membrane was intact. CONCLUSIONS: Repopulation of retinal pigment epithelium in the adult primate can occur rapidly and can support the repair of damaged photoreceptors following submacular surgery.

Animals↗
PubMed1992

Explorations of otic transplantation.

Embryonic rat inner ears were transplanted to the anterior chamber of the eyes of adult rats. While considerable development was evident, the structures present were limited to the vestibular division. We hypothesized that this selective survival could be due to the rate of vascularization. To test the effects of graft vascularization we made transplants in which the internal structures were exposed by removing the apex and base of the developing cochlea. The transplants were rapidly vascularized by the iris. Many of the soft labyrinthine structures of the cochlea from 1-day-old donors showed considerable development, including the spiral limbus, basilar membrane, and organ of Corti. To test the possibility that the cochlea requires inductive or trophic support beyond Embryonic Day 15 (E15), we cotransplanted the embryonic inner ear with developing brain stem. In these transplants, we observed improved development of the cochlea, with spiral ganglion cells and an organ of Corti possessing hair cells, Deiter's cells, and pillar cells. To further address the effect of developing CNS tissue on the development of grafted inner ear, we transplanted E15 inner ears to either the cortex or the brain stem of neonatal rats. In these experiments we have seen evidence of both vestibular and cochlear sensory surfaces. In the cochlea, an organ of Corti-like structure can be seen. The possibility of neural connections with the host brain has yet to be investigated.

Animals↗
PubMed1992

Photoreceptor transplantation: anatomic, electrophysiologic, and behavioral evidence for the functional reconstruction of retinas lacking photoreceptors.

We have investigated the possibility of using transplantation of immature or mature rodent photoreceptors as well as mature human photoreceptors to reconstruct retinas in which photoreceptor degeneration is either inherited or environmentally induced. To this end, we have devised methods for isolating and transplanting the outer nuclear layer (ONL) (e.g., the photoreceptor layer) to the subretinal space of mature rodents. In addition we found that if portions of the inner retina are transplanted along with the intact photoreceptor sheet, photoreceptor organization is better maintained. In ultrastructural studies of the reconstructed retina an outer plexiform-like layer (OPL) is visible at the interface of the transplanted ONL and the host inner nuclear layer, with invaginating ribbon synapses characteristic of those formed by rod photoreceptors evident within this OPL. Ribbon synapses are found only rarely in unreconstructed retina. These results suggest that synaptic connections between transplanted photoreceptors and host cells may be made. Evidence for the potential recovery of function following photoreceptor transplantation is found in visually evoked cortical responses and behavioral responses (pupillary reflex) to light stimulation of the reconstructed eye. These findings suggest the possibility that neural transplantation can reconstruct a sensory end organ--in this case the retina--to restore evoked activity and an appropriate behavioral response to sensory stimulation.

Albinism↗
PubMed1992

Retinal cell and photoreceptor transplantation between adult New Zealand red rabbit retinas.

Adult New Zealand Red (NZR) rabbits were used to determine if the techniques developed in the rat to transplant sheets of photoreceptors could be adapted to larger eyes of the rabbit. Adult donor NZR rabbit retina was cut into small strips, oriented, and drawn up in a small and flat polyethylene tube. By transscleral approach, donor retina was correctly oriented and gently placed into the subretinal space of host retinas that were previously ablated of photoreceptors by intravitreal injection of hemoglobin. Two weeks after surgery, rabbits were terminated and eyes processed for histology. Morphologic evaluation indicated that photoreceptors were transplantable between adult rabbits by adaptation of previously developed methods and that they were well maintained for 2 weeks. Transplanted photoreceptors also appeared to retain nearly normal inner and outer segment (I & OS) morphology and anti-opsin reactivity. Finally, inclusion of the inner retina also appeared to help maintain the correct I & OS apposition to the host retinal pigmented epithelium.

Animals↗
PubMed1992

Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2.

We describe an infant with three unusual features of perinatally acquired herpes simplex virus type 2 encephalitis: onset of illness at 34 days of age, absolute cerebrospinal fluid neutrophilia, and systemic viral dissemination after central nervous system disease. To provide early, effective antiviral therapy, clinicians should be aware of atypical presentations of serious herpes simplex virus infections.

Encephalitis↗
PubMed1990

Photoreceptor rescue in the RCS rat without pigment epithelium transplantation.

Transplantation of normal retinal pigment epithelium (RPE) to the subretinal space has been reported to rescue photoreceptors in the RCS rat. Moreover, the rescue effect was surprisingly large considering the relatively small number of RPE cells transplanted. The reason for this widespread rescue of photoreceptors is not known, nor is the mechanism for outer segment phagocytosis in photoreceptors not apposed to the transplanted RPE cells. This suggests that the rescue effect may not be solely mediated by the transplanted cells. We therefore wished to test whether the transplantation surgery itself might contribute to the rescue of RCS photoreceptors. For these control experiments, we performed the surgery on juvenile RCS rats as described by others for the transplantation of RPE but instead of injecting RPE, we injected saline. We sacrificed the RCS control operates two months following surgery. In the area of the surgery (superior retinal quadrant) the outer nuclear layer (ONL) was up to 8-10 photoreceptor cells thick, while at the extreme inferior margin of the retina the ONL was almost eliminated. To investigate the role of temporary retinal detachment in photoreceptor rescue we repeated the above experiment using our trans-corneal approach to the subretinal space. This procedure results in a large temporary retinal detachment and little or no damage to the choroid and sclera.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Spatial-frequency organization in primate striate cortex.

We measured the spatial-frequency tuning of cells at regular intervals along tangential probes through the monkey striate cortex and correlated the recording sites with the cortical cytochrome oxidase (CytOx) patterns to address three questions with regard to the cortical spatial-frequency organization. (i) Is there a periodic anatomical arrangement of cells tuned to different spatial-frequency ranges? We found there is, because the spatial-frequency tuning of cells along tangential probes changed systematically, varying from a low frequency to a middle range to high frequencies and back again repeatedly over distances of about 0.6-0.7 mm. (ii) Are there just two populations of cells, low-frequency and high-frequency units, at a given eccentricity (perhaps corresponding to the magno- and parvocellular geniculate pathways) or is there a continuum of spatial-frequency peaks? We found a continuum of peak tuning. Most cells are tuned to intermediate spatial frequencies and form a unimodal rather than a bimodal distribution of cell peaks. Furthermore, the cells with different peak frequencies were found to be continuously and smoothly distributed across a module. (iii) What is the relation between the physiological spatial-frequency organization and the regions of high CytOx concentration ("blobs")? We found a systematic correlation between the topographical variation in spatial-frequency tuning and the modular CytOx pattern, which also varied continuously in density. Low-frequency cells are at the center of the blobs, and cells tuned to increasingly higher spatial frequencies are at increasing radial distances.

Animals↗
PubMed1989

Antagonism by growth hormone of insulin-sensitive hexose transport in 3T3-F442A adipocytes.

We have studied the effects of GH on basal and insulin-stimulated hexose transport by 3T3-F442A adipocytes in a hormonally defined serum-free medium. Adipocytes preincubated in defined medium exhibit a low level of hexose transport which is acutely (15 min) stimulated (greater than 5-fold) by insulin (EC50, 0.1-0.2 nM). GH has acute (15-45 min) insulin-mimetic (greater than 2-fold) and chronic (4-48 h) diabetogenic (50-80%) effects on basal and insulin-stimulated hexose transport. The insulin-mimetic effect of GH has a higher EC50 (2 nM) than its diabetogenic effect (EC50, 0.2 nM). Chronic GH exposure decreases the maximal responsiveness (50-80%) and the acute sensitivity (approximately 2-fold) of hexose transport to insulin. Insulin-stimulated transport is more (approximately 5-fold) sensitive to the diabetogenic effect of GH than is basal transport. Insulin binding and degradation were not altered by chronic exposure to GH. The diabetogenic effect of GH may occur at a postinsulin binding level.

Adipose Tissue↗
PubMed1989

Transplantation of photoreceptors to light-damaged retina.

We investigated the possibility of reconstructing light-damaged retinas by photoreceptor transplantation. The outer nuclear layer containing the photoreceptor cells was eliminated in adult albino rat retinas by exposure to constant high-level illumination. Photoreceptors for transplantation were harvested from neonatal rats using a novel isolation technique that maintained the cellular organization of the outer nuclear layer. Transplantation was accomplished using a transcorneal approach to the subretinal space, which minimized trauma to the eye. The retina reattached to the back of the eye with transplanted photoreceptors interposed between the retina and the overlying tissues. Prelabelling with fluorescent dye enabled positive identification of the transplanted cells. The transplanted photoreceptors appeared to survive transplantation for at least 6 weeks and were immunohistochemically reactive for opsin. The antibody staining for opsin identifies the transplanted cells as photoreceptors and indicates that they are still capable of producing visual pigment and therefore may have the capacity to transduce light. These findings indicate that photoreceptors can be transplanted to form a new outer nuclear layer in a damaged mature retina.

Animals↗
PubMed1989

Photoreceptor transplantation in inherited and environmentally induced retinal degeneration: anatomy, immunohistochemistry and function.

In conclusion, we have shown that photoreceptors can be transplanted to retina in which the host's photoreceptors are lost by environmental (constant light) or inherited deficits. Furthermore transplanted photoreceptor cells maintain basic characteristics of normal photoreceptor cells by producing opsin and maintaining an intercellular organization and apposition to the host retina that is similar to that seen in the normal outer nuclear layer. To accomplish this we have devised a method to isolate the intact photoreceptor layer. This is significant because it will be necessary to maintain tight matrix organization if coherent vision is to be restored to the retina compromised by the loss of photoreceptors. We have further developed a surgical approach which minimizes trauma to the eye and allows controlled positioning of sheets of transplanted photoreceptors to their homotopic location within the eye. In addition these methods for transplantation and isolation of photoreceptors could be utilized to prepare and transplant other retinal layers so that selected populations of retinal cells can be used in other neurobiological investigations. Photoreceptors can be transplanted when developing or when mature. Not only can mature rat photoreceptors can be transplanted, but we have shown that mature photoreceptors from human donors can be transplanted as well. This is significantly different from neurons which must be immature in order to be transplanted. At present the reason for this difference is not known but has obvious importance for retinal and neural transplantation research in general. Finally, we have shown that transplanted photoreceptors activate the host's dystrophic retina in a light dependent manner that closely resembles the activation pattern seen in normal retina. This finding taken together with our results showing that human photoreceptors can be transplanted presents the possibility that some forms of human blindness might eventually be ameliorated by photoreceptor transplantation. The authors are grateful to A. I. Cohen, and N. W. Daw for helpful discussions; to C. Barnstable for gifts of antibody; and to J. Lett for excellent technical assistance. This work was supported by grants from NIH, National Retinitis Pigmentosa Foundation, the Monsanto Company; and an Alfred P. Sloan Fellowship to MSS.

Age Factors↗
PubMed1988

Functional anatomy of macaque striate cortex. I. Ocular dominance, binocular interactions, and baseline conditions.

A series of experiments was carried out using 14C-2-deoxy-d-glucose (DG) in order to examine the functional architecture of macaque striate (primary visual) cortex. This paper describes the results of experiments on uptake during various baseline (or reference) conditions of visual stimulation (described below), and on differences in the functional architecture following monocular versus binocular viewing conditions. In binocular "baseline" experiments, monkeys were stimulated either (1) in the dark, (2) with a diffuse gray screen, or (3) with a very general visual stimulus composed of gratings of varied orientation and spatial frequency. In all of these conditions, DG uptake was found to be topographically uniform within all layers of parafoveal striate cortex. In monocular experiments that were otherwise similar, uptake was topographically uniform within the full extent of the eye dominance strip, in all layers. Certain other visual stimuli produce high uptake in the blobs, and still another set of visual stimuli (including high-spatial-frequency gratings) produce highest uptake between the blobs at parafoveal eccentricities, even in an unanesthetized, unparalyzed monkey. Eye movements per se had no obvious effect on striate DG uptake. Endogenous uptake in the blobs (relative to that in the interblobs) appears higher in the squirrel monkey than in the macaque. The pattern of DG uptake produced by binocular viewing was found to deviate in a number of ways from that expected by linearly summing the component monocular DG patterns. One of the most interesting deviations was an enhancement of the representation of visual field borders between stimuli differing from each other in texture, orientation, direction, etc. This "border enhancement" was confined to striate layers 1-3 (not appearing in any of the striate input layers), and it only appeared following binocular, but not monocular, viewing conditions. The border enhancement may be related to a suppression of DG uptake that occurs during binocular viewing conditions in layers 2 + 3 (and perhaps layers 1 and 4B), but not in layers 4Ca, 4Cb, 5 or 6. Another major class of binocular interaction was a spread of neural activity into the "unstimulated" ocular dominance strips following monocular stimulation. Such an effect was prominent in striate layer 4Ca, but it did not occur in layer 4Cb. This "binocular" spread of DG uptake into the inappropriate eye dominance strip in 4Ca may be related to the appearance of orientation tuning and orientation columns in that layer. No DG effects were seen that depended on the absolute disparity of visual stimuli in macaque striate cortex.

Animals↗
PubMed1988

Functional anatomy of macaque striate cortex. II. Retinotopic organization.

Macaque monkeys were shown retinotopically-specific visual stimuli during 14C-2-deoxy-d-glucose (DG) infusion in a study of the retinotopic organization of primary visual cortex (V1). In the central half of V1, the cortical magnification was found to be greater along the vertical than along the horizontal meridian, and overall magnification factors appeared to be scaled proportionate to brain size across different species. The cortical magnification factor (CMF) was found to reach a maximum of about 15 mm/deg at the representation of the fovea, at a point of acute curvature in the V1-V2 border. We find neither a duplication nor an overrepresentation of the vertical meridian. The magnification factor did not appear to be doubled in a direction perpendicular to the ocular dominance strips; it may not be increased at all. The DG borders in parvorecipient layer 4Cb were found to be as sharp as 140 micron (half-amplitude, half width), corresponding to a visual angle of less than 2' of arc at the eccentricity measured. In other layers (including magnorecipient layer 4Ca), the retinotopic borders are broader. The retinotopic spread of activity is greater when produced by a low-spatial-frequency grating than when produced by a high-spatial-frequency grating. Orientation-specific stimuli produced a pattern of activation that spread further than 1 mm across cortex in some layers. Some DG evidence suggests that the spread of functional activity is greater near the foveal representation than near 5 degrees eccentricity.

Animals↗
PubMed1988

Functional anatomy of macaque striate cortex. III. Color.

Using spatially diffuse stimuli (or sinusoidal gratings of very low spatial frequency), levels of 14C-2-deoxy-d-glucose (DG) uptake produced by color-varying stimuli are much greater than those produced by luminance-varying stimuli in macaque striate cortex. Such a difference in DG results is consistent with previous psychophysical and electrophysiological results from man and monkey. In DG experiments with color-varying gratings of low and middle spatial frequencies, or with spatially diffuse color variations, DG uptake was highest in the cytochrome oxidase blobs, as was also seen with low-spatial-frequency luminance gratings. High-spatial-frequency, color-varying uptake patterns were shifted to cover both blob and interblob regions in a manner similar to that of the patterns obtained with middle-spatial-frequency luminance stimuli. However, in no instance did chromatic gratings produce uptake restricted to the interblob regions, as with the pattern seen with the highest-spatial-frequency luminance gratings. Thus, DG uptake is relatively higher in the interblob regions when comparing luminance with color-varying gratings that are otherwise similar. It was also possible to show DG evidence for receptive-field double-opponency in the upper-layer blobs, but color sensitivity in layer 4Cb appears single-opponent. The DG results suggest that color sensitivity is also high in the lower-layer (layers 5 + 6) blobs, and that many layer 5 receptive fields are double-opponent. Striate layers 4Ca and 4B-appeared color-insensitive in a wide variety of DG tests; this supports the idea of a color-insensitive stream running from the magnocellular LGN layers through striate layers 4Ca and 4B to extrastriate areas MT and V3. There was also a major effect due to wavelength: long and short wavelengths produced much more uptake than did middle wavelengths, even when all colors were equated for luminance and saturation. No variation with eccentricity was seen in cortical color sensitivity, at least between 0 degrees and 10 degrees.

Animals↗
PubMed1988

Functional anatomy of macaque striate cortex. V. Spatial frequency.

When macaque monkeys view achromatic, sinusoidal gratings of a single spatial frequency, the pattern of 14C-2-deoxy-d-glucose (DG) uptake produced by the gratings is shown to depend on the spatial frequency chosen. When a relatively high (5-7 cycles/deg) spatial frequency is shown binocularly at systematically varied orientations, uptake in parafoveal striate cortex is highest between the cytochrome oxidase blobs (that is, in the interblobs) in layers 1, 2, and 3. In layers 4B, 5, and 6, where the cytochrome oxidase blobs are faint or absent, DG uptake is highest in a periodic pattern that lies in register with the interblobs of layers 2 + 3. When the grating is, instead, of relatively low (1-1.5 cycles/deg) spatial frequency, DG uptake is highest in the blobs, in the blob-aligned portions of layers 1-4B, and in the lower-layer blobs as well. These variations in DG topography are confirmed in stimulus comparisons within a single hemisphere. Presumably, this shift in functional topography within the extra-granular layer is the primate homolog of "spatial frequency columns" shown earlier in the cat (Tootell et al., 1981; Silverman, 1984). In the well-differentiated architecture of primate striate cortex, laminar differences produced by high- versus low-spatial-frequency gratings are visible as well. Gratings of very high spatial frequency produce much higher uptake in 4Cb (which receives input from the parvocellular LGN layers) than in 4Ca (which gets its input from the magnocellular LGN layers). Gratings of low spatial frequency produce the converse result. Presumably, cells in the magnocellular LGN layers and/or in the magnocellular-dominated layer 4Ca have lower average spatial frequency tuning (larger receptive fields) than their counterparts in the parvocellular LGN and/or in striate layer 4Cb. The DG patterns produced by various spatial frequencies also vary with eccentricity, in a manner consistent with known, eccentricity-dependent variations of receptive-field size and spatial frequency tuning. Thus, gratings of a "middle"-spatial-frequency range (4-5 cycles/deg) produce high uptake in the blobs near the foveal representation and high uptake in the interblobs at more peripheral eccentricities, including 5 degrees. This shift in DG topography also includes the transition zone near 3 degrees, where the level of stimulus-driven uptake is as high in the blob regions as it is in interblob regions. Variations in uptake between layers 4Ca and 4Cb, as a function of eccentricity, shift in parallel with the changes in the upper-layer topography.

Animals↗