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Biomedical subjects

S V Girman

Publications and source records attributed to S V Girman.

At least 19 recordsLinked to original sources
PubMed2005

Time course of deterioration of rod and cone function in RCS rat and the effects of subretinal cell grafting: a light- and dark-adaptation study.

To examine how rod and cone function are differentially affected during retinal degeneration, and after subretinal cell grafting, we obtained light- and dark-adaptation curves by recording threshold multiunit responses from the superior colliculus of anesthetized rats. Unoperated RCS dystrophic and non-dystrophic rats were used and the effects of subretinal grafting in dystrophic rats of cells known to limit photoreceptor degeneration were examined. The adaptation curves showed that rod function was severely compromised in unoperated dystrophic RCS rats at low luminance levels, even as early as 21 days of age and that cone thresholds became gradually elevated over time. While cell transplantation preserved both rod and cone photoreceptors, rod function did not recover, although further deterioration of cone threshold responses was prevented. This raises concern that measures of outer nuclear layer thickness may not in themselves be an accurate measure of visual capabilities and efficacy of a restoration strategy.

Adaptation, Ocular↗
PubMed2003

Cortical visual functions can be preserved by subretinal RPE cell grafting in RCS rats.

Photoreceptor loss in the Royal College of Surgeons (RCS) rat is limited by transplantation of retinal pigment epithelial cell lines into the subretinal space prior to the onset of major photoreceptor loss. The purpose of this study was to examine to what extent visual cortical function was rescued by such transplantation and how the degree of rescue correlated with threshold responses recorded in the superior colliculus. To achieve this, single unit responses were recorded from the supragranular layers of cortical area, V1, at 7 months of age at a time when the cortex in these animals is normally non-responsive to specific visual stimulation. The best animals gave cortical responses that were very little different from normal. For the whole group studied, of the eight parameters measured for each cell, only three were significantly less well tuned than in normal non-dystrophic rats. In general, better single unit responses in the cortex were obtained with more photoreceptor rescue and this correlated with better threshold responses. These results indicate that discrete central visual responses can be preserved by subretinal transplantation of a cell line which limits chronic loss of input signal associated with progressive photoreceptor loss.

Animals↗
PubMed2002

Preservation of visual responsiveness in the superior colliculus of RCS rats after retinal pigment epithelium cell transplantation.

The dystrophic RCS rat undergoes progressive photoreceptor degeneration due to a primary defect in retinal pigment epithelial (RPE) cells. This has a major impact on central visual responsiveness. Here we have examined how functional deterioration is contained by subretinal transplantation of immortalized human RPE cells. Transplantation was done at three to four weeks of age prior to significant photoreceptor loss and recipients were kept on cyclosporin. At six months of age, sensitivity maps and multi-unit response properties were obtained across the visual field by recording at 76 equidistant sites encompassing the whole superior colliculus.A significant degree of functional protection, both in terms of area of responsive retina and response characteristics was observed following RPE transplantation. At best, the sensitivity, latency of onset, and response rise time were all maintained within normal ranges and this was achieved with no more than half of the normal complement of photoreceptors. Although partial, the degree of anatomical preservation (both in terms of outer nuclear layer thickness and area of rescue) correlated well with the level of preserved visual sensitivities. Sham injections also resulted in rescue, though the area of preservation was strictly confined to the needle injury site and the response properties were significantly worse than with RPE injections. This study shows that central physiological responsiveness and correlated retinal morphology can be preserved in an animal model of retinal disease by implantation of an immortalized cell line. The use of retinal sensitivity measurements provides a background for assessing higher visual functions in these animals and a direct comparison for human perimetry measures.

Action Potentials↗
PubMed2001

Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats.

Royal College of Surgeons rats are genetically predisposed to undergo significant visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE) cells. By using this model, we have examined the efficacy of subretinal transplantation of two independent human RPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensively characterized genetically engineered human RPE cell line (h1RPE7), which expresses SV40 large T (tumor) antigen, were evaluated separately. Both lines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified human RPE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RPE dysfunction.

Animals↗
PubMed2001

Progressive visual sensitivity loss in the Royal College of Surgeons rat: perimetric study in the superior colliculus.

The Royal College of Surgeons rat has a retinal pigment epithelial cell defect which causes a progressive loss of rods occurring primarily over the first few months of life. We have studied the consequences of this degenerative process on visual sensitivity across the visual field. Sensitivities were determined in the superior colliculus for unit responses recorded from 22 days up to one year of age from sites encompassing the whole visual field representation. Following visual sensitivity assessment, retinae were examined anatomically at the light and electron microscopic level. At 22 days of age, sensitivities in dystrophic rats were comparable to those of non-dystrophics at any age (40+/-1 and 41+/-1dB, respectively), despite the fact that signs of degenerative events were clear at the electron microscopic level, including presence of pyknotic photoreceptor nuclei, disorganised outer segments and accumulation of debris. However, loss in sensitivity was first detected only at 28-36 days of age (27+/-4dB). From then on, sensitivities progressively decreased to reach a plateau by 180-240 days (4+/-2dB). Starting around 90 days and onward, there was a positive gradient of sensitivities from temporal to nasal field. Drops in visual sensitivity were parallelled by several changes in visual response properties, including prolonged latency, inconsistent responsiveness, appearance of bursting spontaneous activity and activation of units by stimuli presented outside their classical receptive fields. The measure of visual sensitivities by recording visual responses at specific sites in the superior colliculus provides a reliable point-to-point assessment of retinal function comparable to visual perimetry testing in humans. This experimental approach provides the background for answering questions arising during the development of potential experimental therapies for retinal degeneration using animal models like the Royal College of Surgeons rat.

Animals↗
PubMed1999

Receptive field properties of single neurons in rat primary visual cortex.

The rat is used widely to study various aspects of vision including developmental events and numerous pathologies, but surprisingly little is known about the functional properties of single neurons in the rat primary visual cortex (V1). These were investigated in the anesthetized (Hypnorm-Hypnovel), paralyzed animal by presenting gratings of different orientations, spatial and temporal frequencies, dimensions, and contrasts. Stimulus presentation and data collection were automated. Most neurons (190/205) showed sharply tuned (</=30 degrees bandwidth at half height) orientation selectivity with a bias for horizontal stimuli (31%). Analysis of response modulation of oriented cells showed a bimodal distribution consistent with the distinction between simple and complex cell types. Orientation specific interactions occurred between the center and the periphery of receptive fields, usually resulting in strong inhibition to center stimulation when both stimuli had the same orientation. There was no evidence for orientation columns nor for orderly change in optimal orientation with tangential tracks through V1. Responses were elicited by spatial frequencies ranging from zero (no grating) to 1.2 cycle/degree (c/ degrees ), peaking at 0.1 c/ degrees, and with a modal cutoff of 0.6 c/ degrees. Half of the neurons responded optimally to drifting gratings rather than flashing uniform field stimuli. Directional preference was seen for 59% of oriented units at all depths in the cortex. Optimal stimuli velocities varied from 10 to 250 degrees /s. Some units, mainly confined to layer 4, responded to velocities as high as 700 degrees /s. Response versus contrast curves (best fit with Naka-Rushton) varied from nearly linear to extremely steep (mean contrast semisaturation 50% and threshold 6%). There was a trend for cells from superficial layers to be more selective to different stimulus parameters than deeper layers cells. We conclude that neurons in rat V1 have complex and diverse visual properties, necessary for precise visual form perception with low spatial resolution.

Animals↗
PubMed1994

Neocortical grafts receive functional afferents from the same neurons of the thalamus which have innervated the visual cortex replaced by the graft in adult rats.

Electrophysiological and anatomical studies were carried out in parallel to investigate the ability of lateral geniculate body neurons to regenerate axons damaged by the removal of the primary visual cortex and to innervate graft neurons functionally after transplantation of fetal neocortical tissue to a lesion cavity in the brain of adult rats. In electrophysiological experiments neurons of a large portion of the transplants (14/35) displayed visual responses with characteristics resembling closely those of normal primary visual cortex; these transplants also displayed a different degree of restoration of topographically organized visual field representations on them. To demonstrate anatomical regeneration of inputs from the host lateral geniculate body to the graft, injections of FluoroGold were made before grafting into the intact visual cortex for retrograde labeling of the lateral geniculate body neurons. After completion of the microelectrode recordings from the transplants a second dye, Bisbenzimide, was injected into the transplants. The rats with transplants whose neurons displayed responses to visual stimulations contained in the lateral geniculate body neurons with FluoroGold-labeled cytoplasm and Bisbenzimide-labeled nuclei. The presence of double-labeled neurons suggests that the same neurons, the axons of which have terminated in area 17 of the cortex, innervated the transplants functionally through the regeneration of damaged axons.

Animals↗
PubMed1993

Retinal afferents innervate functionally tectal but not neocortical grafts placed in lesioned superior colliculus of adult rats.

Solid pieces of tectum or occipital neocortex derived from 17-day rat fetuses were placed over the lesioned right superior colliculus (SC) in adult rats as sheets retaining the internal structure of the embryonal tissue. The upper laminae of the recipient's SC (approximately up to stratum opticum) were removed by aspiration after the neocortex overlying the SC was aspirated out. Two to 5 months after the operation a microelectrode study of the neuronal electrical activity in the grafts was performed. Recordings from the tectal transplants revealed normal patterns of the spontaneous neuronal activity in all grafts and clear neuronal reactions to visual stimuli in a large portion of them (6 out of 11). Visual reactions in these grafts were recorded from the majority of studied neurons (185/226). The properties of the receptive fields as well as the range of latencies of the reactions corresponded to those characteristic of the normal SC. Topographic representation of the visual field upon the transplants was found. Recordings from the cortical grafts showed an abnormal character of the spontaneous neuronal activity and the absence of reactions to any sensory stimulation of the recipients. The data obtained suggest that regenerating optic axons in adult hosts retain specificity in functional innervation of only appropriate target neurons and can re-establish the topographic representation of the retina upon tectal grafts. Retinal afferents innervate functionally tectal but not neocortical grafts placed in lesioned superior colliculus of adult rats.

Animals↗
PubMed1990

Electrophysiological properties of embryonic neocortex transplants replacing the primary visual cortex of adult rats.

Solid pieces of the occipital neocortex derived from 17-day rat fetuses were placed in a cavity formed by complete unilateral aspiration of the primary visual cortex in adult rats. Vital labeling of the brain with bisbenzimide was used to differentiate grafts from the host brain tissue. 2 to 10 months after operation electrophysiological experiments were performed in which neuronal activity and field potentials in transplants were recorded in response to sensory and electrical stimulation of the host brain. This study shows that in a large portion of the transplants (14 out of 25): (1) the majority of neurons (183/270) are controlled by visual stimuli and many of them respond to electrical stimulation of the lateral geniculate body (53/62) and the homotopic sites of the contralateral neocortex (28/62); latencies of these responses are within the ranges typical of the normal visual cortex; (2) there is a topical representation of the visual field on the transplants; (3) receptive field sizes, the preference to stationary flashes or to moving visual stimuli and the temporal response pattern of the grafted neurons are similar to those of the primary visual cortex. However, the field potentials evoked visually were recorded only in part of the transplants (8/14) which revealed clear neuronal visual responses, and field potential depth profile differed from that in visual cortex in situ. The functional organization of the transplants remained unchanged throughout the long-time testing. Taken together, these results suggest that after primary visual cortex removal, fetal neocortex transplants may be able to replace functionally the damaged neural circuitries of the host brain.

Animals↗
PubMed1989

Normalization of protein synthesis in brain cortex of rats after hypoxia by transplantation of embryonic nervous tissue.

It has been shown autoradiographically using 3H-lysine-3H-glycin mixture that acute hypoxic hypoxia leading to mass diffuse dystrophy of brain cortex neurons in rats causes a statistically significant decrease in the level of protein synthesis in cortical neurons. The biochemical study of the same material using 3H-leucine has demonstrated that the overall level of protein synthesis in the total cortical tissue (in nerve and non-nerve cells) is not reduced after hypoxia probably due to a high resistance of glial and other non-nerve cells to oxygen deficiency. Transplantation of embryonic nervous tissue into the brain of rats exposed to hypoxia results not only in normalization of the structure of a part of dystrophic neurons but also in a statistically significant increase in the level of protein synthesis which is retained up to the end of the experiment (i. e. for 120 days following the operation) in the total cortical tissue and reaches the normal value in neurons as established autoradiographically.

Animals↗
PubMed1988

[Electrophysiologic research on the afferent connections of embryonic neocortex allografts inserted into the projection zones of the cortex in adult rats].

Grafts of the rat fetal neocortex (the 17th-18th day of gestation) were placed into the cavity made by aspiration in the primary visual or somatosensory cortex of adult rats. Electrophysiological studies performed 3-3.5 months later showed that approximately in 50% of animals the neurons of the transplants responded to sensory stimuli of modality specific for cortical regions replaced by the transplant. These responses were elicited from local receptive fields that in some animals revealed topographic organization. Neuronal responses of transplants were elicited by local electrical stimulation of thalamic nucleus projecting to the cortical site of grafting, as by stimulation of contralateral homotopic cortical areas. Latency and temporal patterns of neuronal responses were similar to normal ones. Thus it may be concluded that afferent inputs to the cortical transplants retrace normal cortical inputs. The possible mechanisms of re-innervation of the grafts are discussed.

Afferent Pathways↗
PubMed1988

Changes of DNA synthesis in brain cortical cells after transplantation of embryonic nervous tissue into the brain of rats after hypoxia.

Autoradiographic and biochemical studies with 3H-thymidine have shown that after transplantation of embryonic nervous tissue of rats into the brain of adult rats, intact and subjected to acute hypoxic hypoxia causing mass dystrophy of neurons in the brain cortex of recipients, there occurs stimulation of DNA synthesis in non-nerve cells: glial cells, macrophages and endothelial cells. Stimulation is much more pronounced in the operated hemisphere than in the non-operated one and in intact rats than in hypoxia-subjected ones. On the whole, DNA synthesis was not observed in brain nerve cells except individual neurons located near the wound canal and the transplant.

Animals↗