|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1994 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1993 : ¥1,200,000 (Direct Cost : ¥1,200,000)
(1) A progressive decrease in the mRNA-expression of alpha2,6-sialyltransferase, involving in the terminal sialylation of N-linked glycoconjugates was commonly observed in the process of various types of retinal degeneration using in situ hybridization histochemistry. The mRNA-expression of alpha2,3-sialyltransferase, involving in the terminal sialylation of 0-linked glycoconjugates, was exclusively detected at post-natal day (p) 16 and p18. It is likely that 0-linked sialoglycoconjugates, which are detected in the normal mature photoreceptors, are actively synthesized from P16 to P18 in the rat photoreceptor inner segments, suggesting that the 0-linked sialoglycoconjugates in the photoreceptor layr are stable with little turn over in the mature retina. These suggest that abnormal N-linked glycoconjugates may induce retinal degeneration, whereas genetic defects of 0-linked ones may cause congenital retinal dysplasia.
(2) Comparing the in situ hybridization histochemistry of the peripherin/rds mRNA and electron microscopic examination of free ribosomes in the inner segments, the disparsed and clustered ribosomes correspond to active and inactive types, respectively.
(3) Two genomic DNA clones of mouse alpha2,6-sialyltransferase were isolated by using a Bam H1-Bg1 II-digested fragment of the cDNA of rat alpha2,6-sialyltransferase as a probe. The sequences of the clones were determined for preparing an animal model of retinal degeneration by gene targeting.
(4) The sequence of the exon 6 of genomic DNA coding human alpha2,6-sialyltransferase in the peripheral blood of the patients of retinitis pigmentosa was analyzed using PCR-heteroduplex method. Any point mutation is not yet detected up to the present.