Toyoko Yanagita

Novel mutation at the initiation codon in the Norrie disease gene in two Japanese families

We have identified a new mutation of Norrie disease (ND) gene in two Japanese males from unrelated families; they showed typical ocular features of ND but no mental retardation or hearing impairment. A mutation was found in both patients at the initation codon of exon 2 of the ND gene (ATG to GTG), with otherwise normal nucleotide sequences. Their mothers had the normal and mutant types of the gene, which was expected for heterozygotes of the disease. The mutation of the initiation codon would cause the failure of ND gene expression or a defect in translation thereby truncating the amino terminus of ND protein. In view of the rarity and marked heterogeneity of mutations in the ND gene, the present apparently unrelated Japanese families who have lived in the same area for over two centuries presumably share the origin of the mutation.

Glycohistochemical Study of Light-Induced Retinal Degeneration

We are interested in the physiological roles of the sialoglycoconjugates associated with rod photoreceptor cells, which specifically metabolize sialic acids by balancing sialyltransferase with sialidase (1, 2). Defects of O- and N-linked sialoglycoconjugates may cause retinal dysplasia and retinal degeneration, respectively, in humans (3). Retinal degeneration can be experimentally induced in rats by modification of sialic acids of retinal sialoglycoconjugates (4, 5), but the pathomechanism underlying this degenerative process remains to be clarified.

Glycohistochemical analysis of rat eyelid epithelium

The glycoconjugates in eyelids of adult rats were examined by lectin histochemistry and in situ hybridization histochemistry. Since Maackia amurensis lectin II and jacalin bound to the cell membranes of basal and apical epithelial cells, sialic acid alpha 2,3 galactose (Gal) beta 1,3 N-acetylgalactosamine (GalNAc) sequence is present in the glycoconjugates of their cell membranes. Peanut agglutinin bound to the cell membranes of spinous cells in the middle of the epithelium, suggesting that Gal beta 1, 3 GalNAc sequence is present in their glycoconjugates. The mRNA of Gal beta 1,3 GalNAc alpha 2,3-sialyltransferase was detected in the cytoplasm of the epithelial cells other than the basal cells. This observation suggests that sialoglycoconjugates may be newly synthesized in the spinous and apical cells, while the glycoconjugates in the cell membranes of basal cells may be produced at an early stage of development and are stable without turnover.

Immunohistochemical Localization of MUC 1 Glycoprotein in the Retina

Glycoconjugates on the photoreceptor cell surfaces and in the interphotoreceptor matrix (IPM) are involved in a variety of cell functions. The O-linked glycoconjugates, seen in the filaments of IPM by electron microscopy,’ may connect the neural retina with the retinal pigment epithelium (RPE) in the subretinal space.’ These O-linked glycoconjugates are found on the surfaces of both cone and rod photoreceptors except for the basal one-fourth of the inner segments, about the height of Miiller cell fiber baskets.3 These observations led us to speculate that Olinked glycoconjugates in the IPM may link the RPE-processes to the Miiller cell fiber baskets, on which some acceptors for glycoconjugates may be present. MUC 1 glycoprotein, the first mucin to be cloned, is localized on the apical surfaces of epithelial cells as a transmembrane, polymorphic glycoprotein.4 We recently examined the immunohistochemical distribution of MUC 1 in various tumors of the eyelid, orbit, and eyeball.5 During examination of the eyeball tumors, we noted a preferential distribution of MUC 1 in the retinal region that was free of tumor cells. We report this finding because MUC 1 appears to be one of the acceptors on Miiller cell fibers for the O-linked glycoconjugates in the IPM. One eyeball with retinoblastoma and two eyeballs with choroidal melanoma were enucleated and histopathologically examined; immunohistochemical examination of MUC 1 was done on the tumor-free retinal areas. The eyeballs were immersion fixed with buffer formalin at 4°C overnight, rinsed in Dul-