1994 Fiscal Year Final Research Report Summary
Investigation on the pathobiology of corneal ulcer and the development of new drugs.
| Project/Area Number |
05454479
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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 | Yamaguchi University |
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Principal Investigator |
NISHIDA Teruo Yamaguchi University School of Medicine Department of Ophthalmology, Professor, 医学部, 教授 (80036475)
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| Project Period (FY) |
1993 – 1994
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| Keywords | cornea / collagen / collagenase / interleukin I / interleukin I receptor antagonist / collagenolysis / 3D culture in collagen gel / corneal keratocytes |
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| Research Abstract |
The ultimate purpose of the present study is to seek for the new mode of treatment for the corneal ulceration. For this end, we investigated the regulatory mechanisms of the collagenolysis using the cultured corneal keratocytes in the collagen matrix three dimensionally. Collagenolysis was estimated by measuring the amounts of hydroxyproline in the culture media after acid hydrolysis. The amounts of matrix metalloproteinase (MMP,collagenase) was measured by ELISA assay using the monoclonal antibody against the mammalian MMP.The addition of interleukin 1 (IL-1) stimulated the collagen degradation in a dose dependent manner. Concomitantly, the activities of MMP and the amounts of MMP were increased. Transforming growth factor b and interleukin 1 receptor antagonist inhibited the IL-1 activated collagenolysis in a dose dependent manner. MMP induced by IL-1 was mostly active forms of MMP.These results suggested that IL-1 increased the synthesis and secretion of pro-MMP and plasminogen activator which activates the MMP.It was believed that invaded polymorphonuclear leukocytes (PMN) might play important role in the pathogenesis of corneal ulceration. However, the mixed culture of corneal keratocytes and PMN did not demonstrate the synergistic increase of collagenolysis. Thus, the activated corneal keratocytes at the inflamed cornea may play the major role in collagen degradation of the cornea. These results suggest that the principle cells playd in the corneal ulceration might be the cornea keratocytes compared to the PMN.
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