heparitin-sulfate and Cataract

To investigate the chemical pathology in the blood and lens, in cases of congenital or infantile cataract in children excreting predominantly non-reducing carbohydrates in urine.. Urine samples from children with congenital or infantile cataract, and age and sex-matched controls, were analysed for (i) inherited errors of metabolism, (ii) paper chromatography of sugars, (iii) spectrophotometric assay of glycosaminoglycans (GAG), (iv) cetyl trimethyl ammonium bromide test, (v) electrophoresis using Alcian blue, (vi) ion exchange chromatography with IR 120 resin, and (vii) HPLC for xylose. Blood and lens material were also tested for GAG fragments and xylose. beta Glucuronidase was assayed in lymphocytes and urine.. Of 220 children of both sexes below 12 years of age, with congenital or infantile cataract treated in Sankara Nethralaya, Madras, India, during a period of 2 years, 145 excreted fragments of GAG (heparan and chondroitin sulphates) in their urine. There was no such excretion among the control group of 50 children. The same was found accumulated in the blood and lenses of affected children. In addition, xylose was present in small amounts in the urine and blood and xylitol was present in the lens. There was a significant elevation in the activity of beta glucuronidase in lymphocytes and urine, when compared with normals. All the above findings suggest deranged proteoglycan metabolism. As the urine contained mostly GAG fragments and very little xylose, Benedict's reagent was not reduced. This ruled out galactosaemia.. An increase of beta glucuronidase activity might have caused extensive fragmentation of GAG with resultant accumulation in the blood and lens and excretion in urine. Small amounts of xylose may have come from xylose links between GAG and core protein of proteoglycans. Owing to their polyanionic nature, GAG fragments in the lens might abstract sodium, and with it water, thereby increasing the hydration of the lens. Excessive hydration and the osmotic effect of xylitol from xylose might cause cataract. While corneal clouding has been reported in inborn acid mucopolysaccharidosis, congenital or infantile cataract with deranged metabolism of proteoglycans (acid mucopolysaccharide-xylose-protein complex) is reported in children for the first time.

Topics: Case-Control Studies; Cataract; Child; Child, Preschool; Chondroitin Sulfates; Chromatography; Female; Heparitin Sulfate; Humans; Infant; Infant, Newborn; Lens, Crystalline; Male; Proteoglycans; Spectrophotometry; Xylose

To investigate the possible role of transforming growth factor beta (TGF beta) in lens development and growth, the authors studied the influence of TGF beta, alone and in combination with fibroblast growth factor (FGF), on lens epithelial explants.. Lens explants were prepared from both postnatal and adult rats, and changes during 5 days of culture with growth factor(s) were monitored by light and electron microscopy, immunolocalization of laminin, heparan sulfate proteoglycan and fiber-specific crystallins, and crystallin enzyme-linked immunosorbent assays.. TGF beta induced cells in explants to undergo an extensive and rapid elongation with features that distinguished it from FGF-induced fiber differentiation. TGF beta also induced accumulation of extracellular matrix, capsule wrinkling, cell death by apoptosis, and distinctive arrangements of cells. Standard explants from 10-day-old rats responded to TGF beta only in the presence of FGF. Comparable explants from adult rats or from 21-day-old rats (cultured on a laminin substratum) responded readily to TGF beta whether or not FGF was present.. First, these results suggest a role for TGF beta in regulating normal processes in lens cells such as the production of extracellular matrix and capsule formation. Second, because many of the changes induced by TGF beta resembled changes reported to occur during the formation of various kinds of subcapsular cataracts, the results suggest that detailed studies of factors that influence the ability of lens cells to respond to TGF beta and the bioavailability of TGF beta in the ocular media may provide important insights into the etiology of some forms of cataract.

Topics: Animals; Cataract; Cells, Cultured; Crystallins; Drug Combinations; Epithelium; Extracellular Matrix; Fibroblast Growth Factors; Fluorescent Antibody Technique; Heparitin Sulfate; Laminin; Lens, Crystalline; Microscopy, Electron, Scanning; Rats; Rats, Wistar; Transforming Growth Factor beta