151. Roles of lumican and keratocan on corneal transparency.
- Author
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Kao WW and Liu CY
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Chondroitin Sulfate Proteoglycans chemistry, Chondroitin Sulfate Proteoglycans drug effects, Chondroitin Sulfate Proteoglycans genetics, Corneal Opacity genetics, Corneal Opacity physiopathology, DNA genetics, Humans, Keratan Sulfate chemistry, Keratan Sulfate genetics, Lumican, Mice, Mice, Knockout, Molecular Sequence Data, Molecular Structure, Phenotype, Promoter Regions, Genetic, Proteoglycans chemistry, Proteoglycans deficiency, Proteoglycans genetics, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Chondroitin Sulfate Proteoglycans physiology, Cornea physiology, Keratan Sulfate physiology, Proteoglycans physiology
- Abstract
Lumican and keratocan are members of the small leucine-rich proteoglycan (SLRP) family, and are the major keratan sulfate (KS) proteoglycans in corneal stroma. Both lumican and keratocan are essential for normal cornea morphogenesis during embryonic development and maintenance of corneal topography in adults. This is attributed to their bi-functional characteristic (protein moiety binding collagen fibrils to regulate collagen fibril diameters, and highly charged glycosaminoglycan (GAG) chains extending out to regulate interfibrillar spacings) that contributes to their regulatory role in extracellular matrix assembly. The absence of lumican leads to formation of cloudy corneas in homozygous knockout mice due to altered collagenous matrix characterized by larger fibril diameters and disorganized fibril spacing. In contrast, keratocan knockout mice exhibit thin but clear cornea with insignificant alteration of stromal collaegenous matrix. Mutations of keratocan cause cornea plana in human, which is often associated with glaucoma. These observations suggest that lumican and keratocan have different roles in regulating formation of stromal extracellular matrix. Experimental evidence indicates that lumican may have additional biological functions, such as modulation of cell migration and epithelium-mesenchyme transition in wound healing and tumorgenesis, besides regulating collagen fibrillogenesis.
- Published
- 2002
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