Biomedical subjects
Publications and source records attributed to S Sanyal.
Chronic administration of Malvaviscus conzattii (MCV) flower extract at a dose level of 800 mg/kg b.w. for 30 consecutive days in male rats significantly reduced sperm counts and motility together with histological changes in testes. Mating with these treated animals three weeks following the drug schedule proved to be consistently infertile.
The lens proteins from three lines of congenic mice which are homozygous for the gene retinal degeneration (rd) or retinal degeneration slow (rds) or carrying the normal alleles (normal) were analyzed by SDS-PAGE and by immunological reactivity to specific monoclonal antibodies. The lens proteins of normal, rd, and rds mice showed a similar developmental pattern between postnatal day 0 and postnatal day 30. The expression of the 25000 molecular weight (MW) beta-crystallin polypeptide which appears postnatally in the normal lens was not affected by retinal abnormalities in the mutant mice. It is concluded that the regulation of the 25000 MW beta-crystallin polypeptide is not dependent upon differentiation or maintenance of the photoreceptor outer segments or continued presence of the photoreceptor cells.
Mice homozygous for the rds (retinal degeneration slow) gene fail to develop receptor outer segments and show a slow loss of visual cells that starts from 14-21 postnatal days and results in complete absence at 1 year. In the heterozygous rds/+ mice the development of receptor outer segments is initially retarded. Although a distinct layer of outer segments of moderate length is formed, the disc structures remain disarrayed and form irregular whorls. Autoradiograms of rds/+ retinas show reduced incorporation of [3H]-leucine. Scleral movement of label, resulting from the addition of newly formed discs, is also retarded and appears irregular in comparison with the normal. Phagosomes, containing newly shed disc structures, within the retinal pigment epithelium of rds/+ mice are much larger than normal. Counts taken at different times of the dark- and light periods have shown an abnormally high turnover of phagosomes in the pigment epithelium of the rds/+ mice, with higher than normal peak frequency near the end of the light period, in contrast with the peak frequency in the normal pigment epithelium recorded around the beginning of the light period. Starting at 2 months, a very slow loss of visual cells, much slower than in the homozygous mutants, progresses throughout life. As a result, the outer nuclear layer at the age of 18 months or more is reduced to less than half. Prior to the reduction of the outer nuclear layer, the relative frequencies of the rod and cone perikarya in the rds/+ retina are similar to the normal values. With loss of visual cells, a small increase in the relative frequency of the cone perikarya is recorded in older rds/+ mice. This increase is more noticeable in the central than in the peripheral retina. The significance of the partial expression of the rds gene in the retina of the heterozygous mice in comparison with the changes observed in the homozygous retina is discussed. It is concluded that dose-dependent variation in phenotypic expression is an essential feature in the working of the rds gene.
A series of chimaeric mice were produced by aggregating morulae from rd/rd and normal (+/+) mice. In the retina of chimaeric mice, produced by aggregating morulae of these two genotypes, loss of rd/rd photoreceptor cells results in a patchy distribution of the surviving normal receptor cells. The number of remaining receptor cells vary between individual chimaeras. The inner retinal layers in the chimaeras, as well as in the two parental genotypes remain intact. Electroretinograms were recorded from 16 chimaeric mice, and various parameters were compared with the amount of visual cells present as estimated by the average thickness of the outer nuclear layer. The amplitudes of the a- and b-wave, showed a linear reduction with decreasing thickness of the outer nuclear layer thickness. However, threshold of the b-wave increased only when the thickness of the outer nuclear layer fell to about 25% of the normal thickness while the time-to-peak of the waves did not change appreciably among the chimaeric individuals. These results suggest that the changes in the electroretinogram of the chimaeric individuals are related to the amount of visual cells present in the retina.
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In the subretinal space of albino mice, macrophages appear from the time of eye opening and increase in number for 6 months; thereafter they decline with age. Dark rearing retards the accumulation of these cells, and exposure to constant light results in a rapid increase. Observations suggest that macrophages appear as a response to visual cell decay in albino mice and supplement the phagocytic activity of the pigment epithelium.
In mice, homozygous for the retinal degeneration slow (rds) gene, the photoreceptor cells lack outer segment disc structures, contain low amounts of rhodopsin, and degenerate slowly, while the inner retinal layers remain intact. The electroretinogram (ERG) from 1-month-old mutant mice shows a lower than normal amplitude but the time-to-peak is normal. The ERGs from mutant mice of 2-3 months and 6-7 months of age show a further decline in response amplitude as the receptor cell population is depleted with progress of degeneration while the time-to-peak increases. The ERG is absent in 1-year-old mutant mice which have lost their receptor cells completely. The possible morphological correlations of the ERG and its components in the rds mutant mice are discussed.
In the retina of mice homozygous for the retinal degeneration slow (rds) gene, receptor outer segments failed to develop and typical disc structures were never observed. However, cilia surrounded by a plasma membrane were regularly present. At the time when outer segments grew in the normal retina, the optic ventricle in the mutant showed an accumulation of membrane-bound vesicles of varying size and density. The vesicles declined in frequency at later stages of degeneration. After initial growth, the inner segments in the mutant retina remained stunted but maintained their morphological differentiation, including the ciliary structures. Their number declined with loss of visual cells. In the mutant retina development of synapses, between the receptor cells and the processes of the horizontal cells and the bipolar cell dendrites, followed in normal sequence. Formation of spherule terminals of the rods, with one triad synapse, and of pedicle terminals of the cones, with multiple triad synapses, was recorded in the same way as in the normal retina. With loss of visual cells in the mutant retina, some of the profiles of the surviving spherule terminals showed an increased occurrence of two, three, or more synaptic sites. This growth resulted from enlargement and branching of the ribbons and sprouting from the postsynaptic elements. Similar changes were not observed in the pedicle terminals. The pigment epithelial cells in the mutant mice appeared initially normal, but phagolysosomal structures were absent. However, various inclusion bodies appeared within the pigment epithelial cells following degenerative changes in the retina. In some places, the basal infoldings deepened their furrows while thinning the cytoplasmic part of the epithelium. Failure to form the outer segments and the subsequent lysis of the visual cells appear to be the primary effects of the rds gene, whereas the synaptic growth in the sperule terminals and the changes in the pigment epithelium appear to be consequential to those defects.
Mice, homozygous for the rds gene, fail to develop the receptor outer segments and show a slow reduction of the outer nuclear layer. A series of 13 chimaeric mice was produced by combining morulae from albino rds/rds and pigmented normal (+/+) mice. At 3-4 weeks, variable stretches of visual cells without outer segments were observed together with stretches of visual cells with normal outer segments. The location of these areas was unrelated to the genotype of the overlying pigment epithelium. Phagosomes containing outer segment debris were present in albino pigment epithelial cells, located over normal outer segments, indicating normal functional properties of rds/rds pigment epithelial cells. At 9 months, regions with visual cell loss were observed underlying both types of pigment epithelial cells. Regions showing normal and intermediate thicknesses of the outer nuclear layer were seen more often than regions showing rds/rds type distribution. In another series of eight chimaeras, consisting of albino rds/rds and pigmented rd/rd genotypes, the eyes examined at 22 days showed more pronounced visual cell loss than in the rds----normal retinas at 9 months. Regions of the outer nuclear layer, containing a single row of cone perikarya, were similar to the rd/rd phenotype and differed from the phenotype of the double homozygous rd/rd rds/rds retina, which has a slower rate of degeneration than in rd/rd mice. Visual cell loss in these chimaeras at 9 months was similar to that in the rds/rds retina of the same age. The findings show that the expression of the rds gene, resulting in failure of outer segment development and eventual death of visual cells is unrelated to the genotype of the overlying pigment epithelial cells and suggest that the gene acts within the neural retina and possibly intracellularly in the visual cells.
Cyclic nucleotide metabolism was examined in the retina and in the retinal pigment epithelium (RPE)-choroid complex of the rds mouse (020/A), a mutant in which discrete photoreceptor outer segment disc structures fail to develop. In retinas of both rds and control (Balb/c) mice, cyclic AMP levels peak at 10-15 days (20-25 pmol mg-1 protein). The level drops to about 10 pmol mg-1 at about one month in normal retinas but remains high in affected retinas. Cyclic GMP levels increase five-fold in Balb/c retinas as ROS develop whereas, in affected retinas, the levels remain constant and low (about 5 pmol mg-1). In RPE-choroid, cyclic nucleotide levels are similar in control and affected mice. Cyclic AMP phosphodiesterase (PDE) activity is somewhat higher in affected than in control retinas; conversely, cyclic GMP-PDE is lower. Both cyclic AMP-PDE and cyclic GMP-PDE activities are different in normal and affected RPE-choroid. Thus, although the rds (020/A) mouse belongs to the early-onset photoreceptor dysplasia group of hereditary retinal degenerations on a morphological basis, it does not exhibit high retinal cyclic GMP levels and thus appears to be distinct from other animals exhibiting early postnatal photoreceptor dysfunction.
The lens in the dyl mutant mice shows a persistent lens-ectodermal connection as well as degeneration and extrusion of lens materials after the initial differentiation of the fibres. Immunohistochemical investigation of the ontogeny of the lens crystallins in this developing mutant lens has been carried out using the indirect immunofluorescence staining method with antiserum to adult mouse lens total soluble proteins. The results have been compared with those for coisogenic normal lens used as a control. In both, the first positive reaction was detectable at identical stages of lens development. A rapid increase in the intensity of fluorescence, most marked in the elongating fibre progressing through the equatorial region to the epithelium, was recorded in the mutant as well as in the normal lens. However, the stalk leading to the lens epithelium did not show any reaction. Appearance of vacuoles in the lens nucleus and cortex marked the beginning of degeneration of fibres which otherwise showed strong fluorescence. This was followed by extrusion of lens crystallin materials through the stalk. As a result, the lens became increasingly reduced and malformed but the surviving cells making up the vestigeal lens in the adult showed positive immunofluorescence. The results demonstrate that despite a failure of lens-ectoderm separation in the mutant mice, the ontogeny of the lens crystallins and differentiation of the lens up to a certain stage of development follow an apparently normal course before the commencement of cataractous degeneration.
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Testosterone stimulates the Accessory Reproductive Glands (ARG) and may increase the serum titres of prolactin in castrated male rats. Bromocriptine antagonizes the testosterone-induced alteration of ARG responses; the testosterone antagonistic action of bromocriptine depends on the degree of serum prolactin depletion.
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When pimozide was given to maturing rats, a rise in the level of prolactin in the serum was accompanied by a fall in LH. There was also incomplete initiation of spermatogenesis as well as simultaneous adrenal hypertrophy. Bilateral adrenalectomy failed to prevent hyperprolactinaemia-induced antispermatogenic response, while a significant ameliorating effect was observed with LH, indicating that hyperprolactinaemia influenced the quantitative initiation of spermatogenesis by affecting the secretion of LH.
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