chondroitin-sulfates and Retinitis-Pigmentosa

The RCS rat is a widely studied model of human retinal dystrophies including retinitis pigmentosa. Chondroitin-6-sulphate (C6S) in the interphotoreceptor matrix was localised immunocytochemically in both the normal congenic and dystrophic strains of the RCS rat up to 65 days postnatally. From postnatal days 5 to 15 the distribution of C6S in both strains was similar, being localised in the interstices of developing inner and outer segments and adjacent to the RPE surface. In the normal rats, the distribution of C6S did not change with age. In the RCS rats, however, at postnatal days 20 to 35 staining was observed as a dense band at the junction of inner and outer segments and no staining was observed adjacent to the surface of the RPE. At postnatal day 45 onwards there was a decrease and a complete absence of C6S staining in these rats. This change in the pattern of staining correlated with the morphological observation of the progressive degeneration of photoreceptor cells suggesting that C6S may be important in photoreceptor degeneration in the RCS rat.

Topics: Aging; Animals; Antibodies, Monoclonal; Chondroitin Sulfates; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Photoreceptor Cells; Pigment Epithelium of Eye; Rats; Rats, Mutant Strains; Retina; Retinal Degeneration; Retinitis Pigmentosa

Proteoglycans, extracellular matrix molecules that have been shown to have filtration properties in some tissues, make up a significant proportion of the structural macromolecules of Bruch's membrane. Bruch's membrane may provide a selective filtration barrier between the choriocapillaris and the pigmented epithelium (PE) and outer retina. In this paper, we compare the proteoglycans extracted from metabolically-labeled normal and retinitis pigmentosa (RP) Bruch's membranes. Isolated RP Bruch's membrane proteoglycans were larger than those from normal donor eyes when chromatographed on a column of Sepharose CL-4B. In addition to the increased size, there was also a dramatic increase in the proportion of heparan sulfate proteoglycan being synthesized in RP. Considering the structural and filtration properties of proteoglycans, alterations such as these could affect the functioning of Bruch's membrane and, possibly, the PE and the outer retina.

Topics: Chondroitin Sulfates; Choroid; Chromatography; Dermatan Sulfate; Genes, Dominant; Heparitin Sulfate; Humans; Molecular Weight; Proteoglycans; Reference Values; Retinitis Pigmentosa

Cultured human retinal pigmented epithelium (RPE) synthesized and secreted glycosaminoglycans (GAGs) with the characteristics of chondroitin sulfate, dermatan sulfate, and hyaluronic acid from radioactive precursors. Cells subcultured for up to 18 passages from normal RPE and from the RPE of a patient with X-linked retinitis pigmentosa synthesized and secreted the same types and proportions of GAGs as primary cultures of normal RPE. Extracts of native human interphotoreceptor matrix contained hyaluronic acid and chondroitin sulfate but little or no dermatan sulfate, and the chondroitin sulfate differed in electrophoretic mobility and enzyme susceptibility from the chondroitin sulfates secreted by cultured RPE. Cultured human choroidal cells and cultured human skin fibroblasts secreted a much higher proportion of hyaluronic acid than cultured RPE. This study demonstrates that the profile of GAGs synthesized from radioactive precursors and secreted by cultured human RPE is a specific and stable characteristic of these cells that is retained even after extensive proliferation in vitro.

Topics: Adolescent; Adult; Aged; Cells, Cultured; Child; Chondroitin Sulfates; Choroid; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Fibroblasts; Glycosaminoglycans; Humans; Hyaluronic Acid; Middle Aged; Pigment Epithelium of Eye; Retinitis Pigmentosa