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  • The EMBO Journal (2002) 21, 1535 - 1544
  • doi:10.1093/emboj/21.7.1535

Lack of collagen XVIII/endostatin results in eye abnormalities

Naomi Fukai1,8, Lauri Eklund2,8, Alexander G. Marneros1,8, Suk Paul Oh3, Douglas R. Keene4, Lawrence Tamarkin5, Merja Niemelä2, Mika Ilves6, En Li7, Taina Pihlajaniemi2 and Bjorn R. Olsen1

  1. Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
  2. Collagen Research Unit, Biocenter and Department of Medical Biochemistry, University of Oulu, Oulu, FIN-90014, Finland
  3. Department of Physiology, University of Florida, Gainesville, FL 32610, Finland
  4. Portland Imaging Center, Shriners Hospitals for Children, Portland, OR 97201, Finland
  5. CytImmune Sciences, Inc., College Park, MD 20740, Finland
  6. Biocenter and Department of Physiology, University of Oulu, FIN-90014, Finland
  7. Cardiovascular Research Division of Massachusetts General Hospital, Boston, MA 02114, USA
  8. N.Fukai, L.Eklund and A.G.Marneros contributed equally to this work

Correspondence to:

Bjorn R. Olsen, E-mail: bjorn_olsen@hms.harvard.edu

Received 31 October 2001; Accepted 5 February 2002; Revised 31 January 2002

Mice lacking collagen XVIII and its proteolytically derived product endostatin show delayed regression of blood vessels in the vitreous along the surface of the retina after birth and lack of or abnormal outgrowth of retinal vessels. This suggests that collagen XVIII/endostatin is critical for normal blood vessel formation in the eye. All basement membranes in wild-type eyes, except Descemet's membrane, showed immunogold labeling with antibodies against collagen XVIII. Labeling at sites where collagen fibrils in the vitreous are connected with the inner limiting membrane and separation of the vitreal matrix from the inner limiting membrane in mutant mice indicate that collagen XVIII is important for anchoring vitreal collagen fibrils to the inner limiting membrane. The findings provide an explanation for high myopia, vitreoretinal degeneration and retinal detachment seen in patients with Knobloch syndrome caused by loss-of-function mutations in collagen XVIII.

  • Keywords:

    • collagen XVIII,
    • endostatin,
    • eye abnormalities,
    • immunogold labeling,
    • knockout mice