2005 Fiscal Year Final Research Report Summary
Pharmacological control of genetic deficient in corneal dystrophies
| Project/Area Number |
16591768
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Ophthalmology
|
|---|
| Research Institution | JUNTENDO UNIVERSITY |
|---|
Principal Investigator |
MURAKAMI Akira Juntendo University, Dept of Ophthalmology, Professor, 医学部, 教授 (90157743)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJIMAKI Takuro Juntendo University, Dept of Ophthalmology, Assistant Professor, 医学部, 講師 (50333042)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | corneal dystrophy / Gelatinous drop-like corneal dystrophy / M1S1 / amyloid / lactoferrin / chymase / JAM-1 / laminin 5 |
|---|
| Research Abstract |
Gelatinous drop-like corneal dystrophy (GDLD) is an autosomal recessive disorder characterized by severe corneal amyloidosis. We focused on the studying of GDLD, because it is one of the most server corneal dystrophies. M1S1 gene had been isolated as a responsible gene and detected the disease-causing mutations. In this study, our protein expression analysis showed that the normal M1S1 product was accumulated at the cell-to-cell contact borders, but the mutant product did not. We and other researchers showed that the amyloid deposits in GDLD contain lactoferrin. The mutations result in a disturbance of cell-cell adhesion function and contribute to the pathogenesis of amyloid deposition. The pathological condition of corneal epithelium may allow the accumulation of lactoferrin within corneal tissue from the tears. Our studies show that some inflammatory mediators are induced in corneal tissue by lactoferrin and also the mast cell chymase also decreases the barrier function of corneal epithelial cell. We hypothesize that pharmacological enhancement of cell adhesion and controlling the expression of chymase-related mediators may reduce the severity of GDLD phenotype. The exogenous laminin-5 application and up-regulation of JAM-1 gene are now applying for in vitro experiments. And pharmacological screening for suppression of chymase activity is also ongoing.
|
