1994 Fiscal Year Final Research Report Summary
Analysis of photoreceptor cell-specific retinol dehydrogenase gene in the patient with retinitis pigmentosa.
| Project/Area Number |
05454467
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | Tohoku University |
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Principal Investigator |
ISHIGU Sei-ichi Tohoku University School of Medicine, Ophthalmology, Assistant Professor, 医学部, 講師 (20111271)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAI Makoto Tohoku University School of Medicine, Ophthalmology, Professor, 医学部, 教授 (90004720)
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| Project Period (FY) |
1993 – 1994
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| Keywords | retinol dehydrogenase / cDNA / primary structure / gene / photoreceptor cells / retinitis pigmentosa |
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| Research Abstract |
In the visual cycle, all-trans retinal from bleaching rhodopsin is converted to all-trans retinol by all-trans specific retinol dehydrogenase in the rod outer segments (ROSRDH) of photoreceptor cells. All other reactions from all-trans retinol to 11-cis retinal occur in the retinal pigment epithelium (RPE). The 11-cis retinal formed is delivered to rod outer segments (ROS) to regenerate rhodopsin. Since a deficiency of the retinol dehydrogenase possibly causes the accumulation of toxic all-trans retinal derived from rhodopsin photolysis, it can be assumed that the enzyme is the action site of the retinal degeneration gene.
Previously, we purified the retinol dehydrogenase from bovine retinal rod outer segments. The enzyme is a membrane-bound, 37kDa protein and specifically localized in outer segments of photoreceptor cells as demonstrated by light microscopic immunocytochemistry. We attempted the cloning and sequencing of the cDNA for the bovine photoreceptor retinol dehydrogenase. The clone screened by the use of the antibody encodes an amino acid sequence in which amino terminus was identical to that of the purified protein. ROSRDH of photoreceptor cells had little similarity with the RPERDH (10%) but had a consensus sequence of the active sites of SCADs. Although ROSRDH does not have a typical consensus sequence GXXXGXG for the cofactor binding site (NAD,NADP or its reduced formes), a glycine rich region exists in the C-teminus region.
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