Search PubMed⌕ Search

Biomedical subjects

S Sanyal

Publications and source records attributed to S Sanyal.

At least 91 records · Page 5Linked to original sources
PubMed1988

Retinal damage by constant light in chimaeric mice: implications for the protective role of melanin.

Adult chimaeric mice, containing varying proportions of albino and pigmented cells in their ocular tissues, were exposed to constant light for 5 weeks and the distribution of the surviving rod perikarya in the retina and of the pigmented cells in various eye tissues were compared. In chimaeras which were mostly albino, the retinal lesion was similar to that in pure strain albino mice; in chimaeras with relatively more pigmented cells in their ocular tissues, the retina was unaffected as in fully pigmented mice. In chimaeras with amounts of pigmented cells in their ocular tissues varying between these two ends, lesions of intermediate degrees could be observed. Surviving rod cells in such chimaeric retinas were always found in regions adjoining the periphery. The location of the rod perikarya in such regions did not show an exact correlation with that of the overlying pigmented cells but regions of the outer nuclear layer with surviving rod perikarya were generally located in the half or quarter of the retina in which the overlying pigment epithelium also contained more pigmented cells than in the other regions. The proportions of the surviving photoreceptor cells varied between such chimaeras. The lesion appeared to be less extensive in individuals with more pigmented cells in the epithelium but no exact correlation was recorded. The findings suggest that while pigmentation in the iris reduces the amount of light reaching the retina, melanin in the pigment epithelium, in addition to preventing light reflection, may also play an antitoxic role, possibly as an antioxidative agent.

Albinism↗
PubMed1988

Development and degeneration of retina in rds mutant mice: analysis of interphotoreceptor matrix staining in chimaeric retina.

Chimaeric mice were produced by aggregating two morulae--one of homozygous rds mutant and another from a strain of mice with normal retina, which also differed in colour genes. The interphotoreceptor matrix in the retinal sections of these chimaeras was studied histochemically. In sections, stained with colloidal iron, regions with rds/rds photoreceptor layer, characteristically lacking the outer segments, showed more intense staining of the interphotoreceptor matrix, while regions with normal receptor outer segments showed less intense staining of the matrix. In sections, stained with toluidine blue, rds/rds regions showed more intense reaction along the pigment epithelial--photoreceptor interface and less intense reaction over the inner segments in comparison to the regions with normal photoreceptors. These differential staining reactions were independent of the overlying retinal pigment epithelial cell genotype and resembled the reaction patterns in the retina of pure strain controls of the same age. Small patches, showing rds/rds type staining were also observed within areas which appeared normal. We suggest that the altered properties of the interphotoreceptor matrix in the rds retina result from gene expression within the photoreceptor cells.

Animals↗
PubMed1988

Accumulation of glial fibrillary acidic protein in Müller radial glia during retinal degeneration.

Müller radial glia accumulate glial fibrillary acid protein (GFAP) in response to retinal injuries. We have studied the changes in cellular localization of GFAP in genetically caused retinal dystrophy in strains of cat and mouse: Abyssinian cats with progressive retinal dystrophy, and mice homo- and heterozygous for the retinal degeneration (rd) and retinal degeneration slow (rds) genes. The following observations were made: (1) Glial fibrillary acid protein-immunoreactive (GFAP-IR) radial Müller glia are present in normal cat and mouse retinae. (2) There is a general increase with age in numbers of GFAP-IR radial Müller glia, and other GFAP-IR elements in the retina of cat and mice with hereditary retinal dystrophy. (3) The increase in GFAP-accumulating Müller cells seems to proceed from peripheral to central retina in both cats and mice. This might reflect the direction of photoreceptor degeneration, which proceeds in the same direction in the retinal dystrophic cat and in mice bearing the rds gene. However, in the rd mouse photoreceptor degeneration proceeds from central to peripheral retina, indicating that GFAP accumulation is not a local direct effect of photoreceptor damage. (4) Comparing the different mutant mouse strains, there seem to be qualitative differences in the distribution of GFAP-IR elements. The numbers of tangential elements and fibrillary tangles in the inner plexiform and nuclear layers are highest in the +/+ rds/rds retina, followed by the +/+ rds/+, whereas such elements appear to be more scarce in rd/rd rds/rds, followed by the rd/rd +/+ and +/+ +/+ retinae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Synaptic changes in the terminals of rod photoreceptors of albino mice after partial visual cell loss induced by brief exposure to constant light.

Albino mice were exposed to constant light for 7 days and were then transferred to periodic light. After initial photic damage and partial cell loss, the remaining visual cells recovered and survived as a stable population. Regions of the outer nuclear layer containing 4-6 rows of nuclei were more affected than those containing 6-10 rows. Changes in the synaptic structures in the receptor terminals of these two regions were recorded after varying survival periods. Some of the rod terminals had multiple synaptic ribbons and larger numbers of horizontal cell processes and bipolar cell dendrites. The number of terminals with multiple ribbons increased during recovery in periodic light. Morphometry demonstrated that the perimeters of horizontal and bipolar cell processes within the rod terminals were significantly larger than those in age-matched control mice, especially 4 weeks after recovery; they remained significantly larger than controls after 2 and 3 months. We suggest that partial loss of rod cells within a group of cells that are synaptically related to a common bipolar or horizontal cell results in synaptic growth inside the terminals of the surviving cells.

Albinism↗
PubMed1987

Development and degeneration of retina in rds mutant mice: ultraimmunohistochemical localization of opsin.

In normal retina the developing photoreceptor cells first show presence of opsin over the distal ends of the ciliary protrusions. In a fully differentiated cell intense activity is seen over the rod outer-segment discs; some activity is also seen over the Golgi zone and near the distal ends of the inner segments but the other parts of the receptor cell appear negative. In the pigment epithelium opsin is seen only over phagosomes containing rod outer segment debris. In the homozygous rds mutant retina, developing receptor cells show opsin activity over the ciliary protrusions as in the normal. These ciliary protrusions grow in size and show increased opsin activity and presumably constitute the site of phototransduction in the mutant retina. Although typical disc structures remain lacking, variable amounts of immunopositive, irregular, membranous structures are occasionally observed. The inner segments in the mutant cells show very little immunoreactivity but the perikarya and the spherule terminals show increased immunoreactivity in comparison with the normal. At the onset of degeneration, some of the receptor cells in the mutant retina show extrusion of small, membrane-bound vesicles which are immunopositive for opsin. Some receptor cells undergoing lysis disintegrate and also add to the opsin-positive vesicular structures in the interphotoreceptor space. The vesicles are phagocytized by pigment epithelial cells. In older mutant mice at an advanced stage of degeneration, the receptor cells show reduced opsin activity. In heterozygous mutant mice the outer segments are reduced in length and the discs are abnormal in form. However, the intensity and the pattern of opsin localization in the outer segments and at other sites are similar to normal.

Animals↗
PubMed1987

Ontogeny of alpha-crystallin polypeptides during the lens development of a mutant mouse.

The ontogeny of alpha A, alpha B and alpha Ains polypeptides of the alpha-crystallin was investigated by the indirect immunofluorescence staining method with antibodies directed against these three polypeptides in a mutant mouse strain called dyl (27). In this strain cataractogenesis starts around day 16 of lens development but the early development of the lens and the ontogeny of lens crystallins do not differ from the normal genotype (29). The polypeptides were fractionated from normal adult Swiss albino mice total native alpha-crystallin by SDS gel electrophoresis, extracted, lyophilized and injected into young rabbits for production of the antibody. The isolated polypeptides were controlled by SDS gel re-electrophoresis and the antibodies were tested against rat lens native alpha-crystallin by immunoblotting. alpha A and alpha Ains antibodies cross reacted, while alpha B did not show any cross reaction. Results presented here show that alpha A and alpha B appear simultaneously while alpha Ains was detectable at a later stage of lens development. These results are discussed.

Animals↗
PubMed1987

Phospholipid dependence of rat brain microsomal glucose-6-phosphate phosphohydrolase.

Partial lipid removal of rat brain microsomes by acetone-butanol extraction resulted in 32% loss of activity of glucose-6-phosphate phosphohydrolase (G-6-Pase) and an increase in Km and energy of activation (Ea) of the enzyme while the Vmax was lowered. The activity was restored by supplementation of microsomal total phospholipid (PL) and phosphatidylcholine (PC) in sonicated dispersions but not with neutral lipids, phosphatidyl ethanolamine, sphingomyelin, phosphatidylglycerol and cholesterol. In both intact and delipidated membranes, the activity was decreased by sodium deoxycholate and enhanced by dimethylsulfoxide. Egg yolk PC and asolectin influenced the activity to the extent of that produced by microsomal PC. PC increased the Km of the enzymatic reaction in intact microsomes but decreased the same in disrupted membrane while the Vmax was not affected in both the membranes. Addition of PC into the assay system lowered Ea of the reaction in both the membrane systems. However, there was no break observed in the Arrhenius plot. Ability of liver nonspecific lipid transfer proteins to introduce alien PL into brain microsomes was used to study lipid dependence of G-6-Pase and investigation of membrane-enzyme interrelationship. Protein catalyzed transfer of egg PC from a donor PC-cholesterol unilamellar liposomes resulted in substantial increase in microsomal membrane PC and total PL and a net reduction in the enzyme activity was observed in intact and delipidated membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cellular site of expression and genetic interaction of the rd and the rds loci in the retina of the mouse.

In the retina of mice, the two genes, rd and rds, produce retinal degeneration. Depending on allelic combination and gene dosage at these loci, four different genotypes with distinct phenotypic traits and rates of photoreceptor cell loss are recognized. The cellular site of gene action and the nature of interaction, resulting in the variegation of the retinal phenotypes have been analyzed by comparing gene expression in the retina of pure line (unigenotypic) mice, and in the retina of chimaeric mice, experimentally produced by aggregating embryos of different genotypic constitution. The findings suggest that both rd and rds genes act intracellularly within the photoreceptor cells. The primary expression of the genes, producing specific phenotypic alterations of the photoreceptor cells, are invariant and are not affected by extracellular factors. The lethal effects of the genes, on the other hand, resulting in specified rates of photoreceptor cell death, are influenced by both genetic (intracellular), and environmental factors.

Alleles↗
PubMed1986

Development and degeneration of retina in rds mutant mice: effects of light on the rate of degeneration in albino and pigmented homozygous and heterozygous mutant and normal mice.

The effect of light on the rate of visual cell loss in mice afflicted by the rds (retinal degeneration slow) gene was analyzed by comparing the changes in the thickness of the outer nuclear layer. Visual cell loss in the pigmented, homozygous mutant mice, maintained in cyclic light, is slightly slower than in the albino mutant mice. In the pigmented mutant mice, exposed to constant light, and in the albino mutant mice, reared in darkness, rate of cell loss is not significantly altered. In the albino animals exposed to constant light, the rate of cell loss is faster in the homozygous mutant than in the normal, and intermediate in the heterozygous mutant retina. The accelerated cell loss in the mutant retina progresses from the centre to the periphery, and affects the rods earlier than the cones. This resembles the photic lesion in the normal retina but is unlike the genetic lesion in the mutant retina which appears to progress from the periphery to the centre and affects both rods and cones. It is concluded that the visual cells in the retina of rds mutant mice are more vulnerable to photic damage than those in the retina of normal mice.

Albinism↗
PubMed1986

Effect of acute sublethal and chronic administration of DDT (chlorophenotane) on brain lipid metabolism of rhesus monkeys.

Either a single oral dose of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl) ethane (DDT), 150 mg/kg body weight or a long-term chronic dose of the pesticide, 10 mg/kg body weight daily for 100 days was administered to rhesus monkeys and the level of various lipid classes was studied in the brain. A significant decrease was observed in total lipid, unesterified cholesterol and phospholipid (PL) level. Individual PL fractions showed a generalized pattern of reduction, so also did the cholesterol (chol)/PL ratio. Sphingomyelin (SM) registered a significant increase, while no significant alteration was observed in the brain galactolipid and ganglioside level. Lipid lowering effect of DDT was more pronounced in the chronic group. Lipids associated with the myelin sheath were found to be more resistant to pesticide injury, while cholesterol and PL metabolism were more affected.

Animals↗
PubMed1986

Genetic expression of cyclic GMP phosphodiesterase activity defines abnormal photoreceptor differentiation in neurological mutants of inherited retinal degeneration.

We have examined cyclic GMP concentrations, guanylate cyclase activities, and cyclic GMP phosphodiesterase (PDE) activities in developing retinas of congenic mice with different allelic combinations at the retinal degeneration (rd) and retinal degeneration slow (rds) loci. Although guanylate cyclase activities were found to be uniformly low in the mutant retinas, striking differences in PDE activity and cyclic GMP levels were observed in retinas of the various genotypes. Homozygous rds mice, which lack receptor outer segments, showed reduced retinal PDE activity and cyclic GMP concentration in comparison to normal animals. In heterozygous rds/+ mice with abnormal outer segments, the levels were intermediate. In retinas of homozygous rd mice, PDE activity was lower than in rds retinas and cyclic GMP levels were much higher. In mice homozygous for both rd and rds genes, retinal PDE activities were even lower than in single homozygous rd mice; the cyclic GMP level reached the same high value as in the rd animals, persisted for a longer time at this high level, and did not correlate with the rate of photoreceptor cell loss. Thus, a marked variation in PDE activity appears to be the major manifestation of abnormal outer segment differentiation and eventual degeneration of photoreceptor cells in these neurological mutants. An increased cyclic GMP level seems to be an essential corollary in the expression of the rd gene even in the absence of outer segments, but it appears unlikely that an abnormally high nucleotide level in itself causes photoreceptor cell death.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Development and degeneration of retina in rds mutant mice: observations in chimaeras of heterozygous mutant and normal genotype.

In homozygous rds mutant mice the photoreceptor cells lack outer segment discs and slowly degenerate. In the heterozygotes the receptor cells develop abnormal outer segments and show altered disc shedding properties as revealed by the pigment epithelial phagosome content. The receptor cells also degenerate at a slower rate than in the homozygotes. The nature of the interaction resulting in dilution of the retinal lesion in the heterozygous retina was analysed in a series of chimaeras consisting of rds/+ and +/+ genotypes, which also differed in colour genes. In 64% of the chimaeras (18 out of 28) presence of both rds/+ and +/+ types of photoreceptors could be detected by electron microscopy. The relative proportion and patch size of the two components varied greatly between individuals but the location of the two types of photoreceptors was not related to the genotypes of the overlying pigment epithelial cells. Frequent occurrence of abnormally large phagosomes, resembling the rds/+ phenotype, was noted regularly in both rds/+ and +/+ types of pigment epithelial cells located above rds/+ types of receptors, but not in the cells of either genotype located above normal receptors. In the eyes examined at 12-18 months, localized and partial depletion of the perikaryal population in the outer nuclear layer was observed, and the location of such areas was also unrelated to the genotypes of the pigment epithelial cells. These findings confirm that the rds gene acts within the neural retina and possibly within the receptor cells and further show that the genetic interaction between the rds gene and its normal allele in the retina of the heterozygous mice takes place within the receptor cells.

Animals↗
PubMed1985

Immunoassay of rod visual pigment (opsin) in the eyes of rds mutant mice lacking receptor outer segments.

In 020/A mice, homozygous for the retinal degeneration slow (rds) gene, the photoreceptor cells fail to develop outer segments, and in the absorption spectra of retinal extracts the rhodopsin peak is lacking. Application of an enzyme-linked immunoassay using antisera against bovine opsin shows, however, that opsin is present in the homozygous mutant retina (0.010 nmol/eye) at 3% of the level of the normal retina (0.38 nmol/eye) of Balb/c mice. In the retina of heterozygous mice the opsin level (0.19 nmol/eye) is about half of the normal. Detection of opsin in the rds mutant retina demonstrates the functional basis for the reported electroretinographic response and light-mediated reduction in cyclic nucleotide levels in this mutant.

Animals↗
PubMed1985

Inosine diphosphatase as a histochemical marker of retinal microvasculature, with special reference to transformation of microglia.

Nucleoside diphosphatase (IDPase), localized using inosine diphosphate as substrate, allows the selective staining of blood vessels and cells of vascular origin, such as macrophages and microglia, whereas the neuroglial, the neuronal and the pigment epithelial cells remain unstained. The staining pattern observed in the retina of mouse, rat, cat and monkey are similar; some apparent quantitative differences reflect species differences in the distribution of retinal microvasculature. At the electron-microscopic level, most of the enzyme activity in the blood vessels appears to be located along the outer wall. The cell membrane, parts of the smooth endoplasmic reticulum and the nuclear membrane in the microglial perikarya appear positive; profiles of microglial processes are intensely stained. In the developing eyes of rats and mice, the blood vessels are stainable from the earliest stage of their appearance. An array of amoeboid cells precede the growing blood vessels and spread out over the future vascularized part of the retina. These cells eventually develop characteristic microglial features, and extend many elongated and branched processes between the neuroepithelial cells while remaining in contact with, or in close proximity to, the blood vessels. Intense IDPase activity in the microglial cells, in contrast to the absence of the enzyme in the neuroglial Müller cells, suggests that microglia are involved in phosphate metabolism and indicates functional compartmentalization within the glial tissue lying between the blood retinal barrier and the retinal neurons.

Acid Anhydride Hydrolases↗