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Abstract #12550 Published in IGR 7-3
Involvement of inflammation, degradation, and apoptosis in a mouse model of glaucoma
Zhou X; Li F; Kong L; Tomita H; Li C; Cao WJournal of Biological Chemistry 2005; 280: 31240-31248
Glaucoma is a common cause of blindness affecting at least 66 million people worldwide. Pigmentary glaucoma is one of the most common forms of secondary glaucoma, and its pathogenesis remains unclear. Interleukin-18 (IL-18) is an important regulator of innate and acquired immune responses and plays an important role in inflammatory/autoimmunity diseases. Using the DBA/2J mouse as an animal model of human pigmentary glaucoma, we demonstrated for the first time that the expression of the IL-18 protein and gene in the iris/ciliary body and level of IL-18 protein in the aqueous humor of DBA/2J mice are dramatically increased with age. This increase precedes the onset of clinical evidence of pigmentary glaucoma, implying a pathogenic role of inflammation/immunity in this disease. We also observed that activated NF-κB and phosphorylated MAPK are increased in the iris/ciliary body of DBA/2J mice, suggesting that both signaling pathways may be involved in IL-18 mediated pathogenesis of pigmentary glaucoma in the eyes of DBA/2 J mice. In addition, matrix metalloproteinase-2 (MMP-2) expression in the iris/ciliary body and the activity of MMP-2 in the aqueous humor are increased whereas tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) expression in the iris/ciliary body is decreased, indicating that the degradation process is involved in this mouse model of pigmentary glaucoma. Furthermore, the expressions of apoptosis-related genes, caspase-8, Fas, FADD, FAP, and FAF, and the activity of caspase-3 are increased in the iris/ciliary body of DBA/2J mice. Elucidation of biochemical and molecular mechanisms of IL-18 participation in the pathogenesis of pigmentary glaucoma should provide approaches for developing improved and targeted treatments to ameliorate this blinding disease. The possibility that altered IL-18 expression in the eye of DBA/2J mice initiates and/or amplifies the pathogenesis of pigmentary glaucoma requires further investigation.
Dr. W. Cao, Dept. of Ophthalmology, University of Oklahoma Health Sciences Center, Dean A. McGee Eye Inst., 608 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA
Classification:
5 Experimental glaucoma; animal models
2.8 Iris (Part of: 2 Anatomical structures in glaucoma)
2.6.3 Compostion (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
