title: Roles of lumican and keratocan on corneal transparency.
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.
authors.affiliation: Department of Ophthalmology, University of Cincinnati, Cincinnati, OH 45267-0527, USA. Winston.Kao@UC.Edu
authors.forename: Winston W-Y
authors.initials: WW
authors.lastname: Kao
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D003315:Cornea / Q000502:physiology*; D003318:Corneal Opacity / Q000235:genetics / Q000503:physiopathology; D004247:DNA / Q000235:genetics; D006801:Humans; D007632:Keratan Sulfate / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000071234:Lumican; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C490948:KERA protein, human; C099280:Kera protein, mouse; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D004247:DNA; D007632:Keratan Sulfate