Age-dependent changes in the expression of matrix components in the mouse eye.

Although the presence of 'cartilage-specific' collagens in the eye has been documented earlier, very little is known about their synthesis rates during ocular development, growth and aging. The purpose of the present study was to follow changes in the mRNA levels and distribution of key components of the extracellular matrix in the eyes of normal and transgenic Del1 mice, harboring a short deletion mutation in the type II collagen gene, during ocular growth and aging. Total RNAs extracted from mouse eyes were studied by Northern analysis for mRNA levels of type I, II, III, VI, IX and XI collagens, biglycan, fibromodulin and decorin. A predominant finding of the present study was the marked reduction in the mRNA levels of type I and II collagens in the eye upon aging. The changes in the mRNA levels of type III and VI collagen and proteoglycans were smaller. Localization of type II and IX collagen in the eye was performed by immunohistochemistry. Despite the reduction in the type II collagen mRNA levels, immunohistochemistry confirmed widespread distribution of the protein also in aging mouse eyes, suggesting its slow turnover. Although the Del1 mutation caused gradual degenerative lesions in the eyes, the distribution of the protein remained essentially unchanged. The widespread distribution and marked downregulation of type II collagen production in the mouse eye upon aging probably explain the gradual development of degenerative lesions, particularly in the eyes of transgenic Del1 mice, where production of mutant type II collagen chains also contributes to the process.

[1]  K. Mark,et al.  Study of differential collagen synthesis during development of the chick embryo by immunofluorescence. I. Preparation of collagen type I and type II specific antibodies and their application to early stages of the chick embryo. , 1976 .

[2]  E. Hay,et al.  Synthesis of two collagen types by embryonic chick corneal epithelium in vitro. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[3]  A. Aszódi,et al.  Mouse models for extracellular matrix diseases , 1998, Journal of Molecular Medicine.

[4]  M. Gordon,et al.  Extracellular matrices of the developing chick retina and cornea. Localization of mRNAs for collagen types II and IX by in situ hybridization. , 1990, Investigative ophthalmology & visual science.

[5]  M. Solursh,et al.  Widespread distribution of type II collagen during embryonic chick development. , 1989, Developmental biology.

[6]  A. Wood,et al.  The transient expression of type II collagen at tissue interfaces during mammalian craniofacial development. , 1991, Development.

[7]  Chia-Yang Liu,et al.  Developmental patterns of two α1(IX) collagen mRNA isoforms in mouse , 1993 .

[8]  P. Davison,et al.  Collagens of the bovine vitreous. , 1991, Investigative ophthalmology & visual science.

[9]  D. Wright,et al.  Structural and functional comparison of type IX collagen-proteoglycan from chicken cartilage and vitreous humor. , 1991, Journal of Biological Chemistry.

[10]  E. Vuorio,et al.  Osteoarthritis-like lesions in transgenic mice harboring a small deletion mutation in type II collagen gene. , 2000, Osteoarthritis and cartilage.

[11]  F. Keeley,et al.  Characterization of collagen from normal human sclera. , 1984, Experimental eye research.

[12]  R. Reed,et al.  Connective tissue biology : integration and reductionism , 1997 .

[13]  J. Rada,et al.  Proteoglycan composition in the human sclera during growth and aging. , 2000, Investigative ophthalmology & visual science.

[14]  M. Clarke,et al.  Stickler's syndrome associated with congenital glaucoma. , 1998, Ophthalmic genetics.

[15]  I. W. Mclean,et al.  PERIODATE-LYSINE-PARAFORMALDEHYDE FIXATIVE A NEW FIXATIVE FOR IMMUNOELECTRON MICROSCOPY , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[16]  E. Vuorio,et al.  Expression of type II and IX collagen isoforms during normal and pathological cartilage and eye development , 1998, Histochemistry and Cell Biology.

[17]  D. Newsome,et al.  Vitreous body collagen. Evidence for a dual origin from the neural retina and hyalocytes , 1976, The Journal of cell biology.

[18]  G. Ville,et al.  Biochemical properties and immunolocalization of minor collagens in foetal calf cartilage , 1982, FEBS letters.

[19]  I. Maumenee.  Vitreoretinal degeneration as a sign of generalized connective tissue diseases. , 1979, American journal of ophthalmology-glaucoma.

[20]  D. McLeod,et al.  Extraction and characterization of the tissue forms of collagen types II and IX from bovine vitreous. , 1994, The Biochemical journal.

[21]  E. Vuorio,et al.  Chondrodysplasia in transgenic mice harboring a 15-amino acid deletion in the triple helical domain of pro alpha 1(II) collagen chain , 1992, The Journal of cell biology.

[22]  D. Heinegård,et al.  Interaction of a 59-kDa connective tissue matrix protein with collagen I and collagen II. , 1989, The Journal of biological chemistry.

[23]  E. Vuorio,et al.  Localization of type II collagen mRNA isoforms in the developing eyes of normal and transgenic mice with a mutation in type II collagen gene. , 1997, Investigative ophthalmology & visual science.

[24]  G. E. Marshall,et al.  Collagens in ocular tissues. , 1993, The British journal of ophthalmology.

[25]  D. Wright,et al.  Vitreous humor of chicken contains two fibrillar systems: an analysis of their structure. , 1988, Journal of ultrastructure and molecular structure research.

[26]  Steinberg Ag,et al.  Hereditary progressive arthro-ophthalmopathy , 1965 .

[27]  T. Linsenmayer,et al.  Monoclonal antibodies to connective tissue macromolecules: type II collagen. , 1980, Biochemical and biophysical research communications.

[28]  K. Cheah,et al.  Expression of the mouse alpha 1(II) collagen gene is not restricted to cartilage during development. , 1991, Development.

[29]  M. Iruela-Arispe,et al.  Differential expression of extracellular proteins is correlated with angiogenesis in vitro. , 1991, Laboratory investigation; a journal of technical methods and pathology.

[30]  L. Ala‐Kokko,et al.  An inbred line of transgenic mice expressing an internally deleted gene for type II procollagen (COL2A1). Young mice have a variable phenotype of a chondrodysplasia and older mice have osteoarthritic changes in joints. , 1993, The Journal of clinical investigation.

[31]  R. Mayne,et al.  Monoclonal antibody against chicken type IX collagen: preparation, characterization, and recognition of the intact form of type IX collagen secreted by chondrocytes , 1985, The Journal of cell biology.

[32]  E. Traboulsi,et al.  The ocular findings in Kniest dysplasia. , 1985, American journal of ophthalmology.

[33]  A. Spallone.  Stickler's syndrome: a study of 12 families. , 1987, The British journal of ophthalmology.

[34]  E. Vuorio,et al.  Specific hybridization probes for mouse type I, II, III and IX collagen mRNAs. , 1991, Biochimica et biophysica acta.

[35]  B. Olsen,et al.  Embryonic chicken cornea and cartilage synthesize type IX collagen molecules with different amino-terminal domains. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[36]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[37]  J. Akiba,et al.  Age-related changes in the molecular properties of vitreous collagen. , 1993, Current eye research.

[38]  S. Mundlos,et al.  Heritable diseases of the skeleton. Part II: Molecular insights into skeletal development‐matrix components and their homeostasis , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[39]  H Kresse,et al.  Interaction of Biglycan with Type I Collagen (*) , 1995, The Journal of Biological Chemistry.

[40]  E. Vuorio,et al.  Ocular Abnormalities in Transgenic Mice Harboring Mutations in the Type Ii Collagen Gene , 1996, European journal of ophthalmology.

[41]  D. Heinegård,et al.  Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon. , 1984, The Biochemical journal.

[42]  R. Mayne,et al.  An analysis by rotary shadowing of the structure of the mammalian vitreous humor and zonular apparatus. , 1991, Journal of structural biology.

[43]  P. Bishop.  Structural macromolecules and supramolecular organisation of the vitreous gel , 2000, Progress in Retinal and Eye Research.

[44]  M. Cremer,et al.  Monoclonal antibodies against bovine type IX collagen (LMW fragment): production, characterization, and use for immunohistochemical localization studies. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[45]  S. Mundlos,et al.  Kniest and Stickler dysplasia phenotypes caused by collagen type II gene (COL2A1) defect , 1993, Nature Genetics.

[46]  B. Olsen,et al.  Secretion of collagen types I and II by epithelial and endothelial cells in the developing chick cornea demonstrated by in situ hybridization and immunohistochemistry. , 1988, Development.

[47]  Immunoassay techniques for the detection of circulating antibodies to collagen following the use of collagen medical devices. , 1992, Clinical materials.