Lack of collagen XVIII/endostatin results in eye abnormalities.
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.
Fukai
Naomi
N
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Eklund
Lauri
L
Marneros
Alexander G
AG
Oh
Suk Paul
SP
Keene
Douglas R
DR
Tamarkin
Lawrence
L
Niemelä
Merja
M
Ilves
Mika
M
Li
En
E
Pihlajaniemi
Taina
T
Olsen
Bjorn R
BR
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D003094:Collagen / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D043170:Collagen Type XVIII; D004195:Disease Models, Animal; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000235:genetics; D005123:Eye / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005124:Eye Abnormalities / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005354:Fibrosarcoma; D015870:Gene Expression; D008222:Lymphokines / Q000235:genetics; D008297:Male; D008545:Melanoma; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012171:Retinal Vessels / Q000254:growth & development; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043170:Collagen Type XVIII; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen