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Ocular and scleral alterations in gene-targeted lumican-fibromodulin double-null mice.

Chakravarti, Shukti; Paul, Jennifer; Roberts, Luke; Chervoneva, Inna; Oldberg, Åke LU and Birk, David E (2003) In Investigative Ophthalmology & Visual Science 44(6). p.2422-2432
Abstract
PURPOSE: To elucidate the role of leucine-rich proteoglycans lumican and fibromodulin in the sclera. METHODS: Lumican- and fibromodulin-null heterozygous mice were intercrossed to obtain wild-type (Lum(+/+)Fmod(+/+)), lumican-null (Lum(-/-)Fmod(+/+)), fibromodulin-null (Lum(+/+)Fmod(-/-)), and double-null (Lum(-/-)Fmod(-/-)) littermates. Axial length was measured on enucleated whole eyes, and ocular structural changes were examined by histology. The morphology of collagen fibrils in the sclera was examined by transmission electron microscopy (TEM). RESULTS: Compared with the ocular axial length in wild type mice, the axial length was increased by 10% in Lum(-/-)Fmod(-/-) (P = 0.02) mice. Retinal detachment was frequent in the double-null... (More)
PURPOSE: To elucidate the role of leucine-rich proteoglycans lumican and fibromodulin in the sclera. METHODS: Lumican- and fibromodulin-null heterozygous mice were intercrossed to obtain wild-type (Lum(+/+)Fmod(+/+)), lumican-null (Lum(-/-)Fmod(+/+)), fibromodulin-null (Lum(+/+)Fmod(-/-)), and double-null (Lum(-/-)Fmod(-/-)) littermates. Axial length was measured on enucleated whole eyes, and ocular structural changes were examined by histology. The morphology of collagen fibrils in the sclera was examined by transmission electron microscopy (TEM). RESULTS: Compared with the ocular axial length in wild type mice, the axial length was increased by 10% in Lum(-/-)Fmod(-/-) (P = 0.02) mice. Retinal detachment was frequent in the double-null and rare in the lumican-null animals. Compared with the wild-type sclera, the sclera in all null mutants was significantly thinner with fewer lamellae (P < 0.05). The double-null sclera contained abnormally large-diameter (120-160 nm) and small-diameter (30-60 nm) collagen fibrils, whereas the fibromodulin-null sclera was enriched for the small-diameter fibrils. The collagen fibril diameter distribution in the lumican-null sclera was similar to that of the wild-type. CONCLUSIONS: An increase in small-diameter fibrils in the fibromodulin-null sclera suggests a key role for fibromodulin in the maturation and assembly of scleral collagen fibrils. That fibril diameter distribution in the lumican-null sclera was comparable to that in the wild type, but severely disrupted in the double null, suggests a role for lumican that is crucial in the absence of fibromodulin. The eyes of Lum(-/-)Fmod(-/-) mice show certain features of high myopia: increased axial length, thin sclera, and retinal detachment. Mutations or altered expression of these proteoglycans may contribute to myopia in humans. (Less)
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organization
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type
Contribution to journal
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published
subject
in
Investigative Ophthalmology & Visual Science
volume
44
issue
6
pages
2422 - 2432
publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
external identifiers
  • wos:000183081700009
  • pmid:12766039
  • scopus:0038147186
ISSN
1552-5783
DOI
language
English
LU publication?
yes
id
20c40bda-e982-4434-8b64-3164d7b580a9 (old id 113747)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12766039&dopt=Abstract
date added to LUP
2007-07-11 11:36:38
date last changed
2018-05-29 10:12:35
@article{20c40bda-e982-4434-8b64-3164d7b580a9,
  abstract     = {PURPOSE: To elucidate the role of leucine-rich proteoglycans lumican and fibromodulin in the sclera. METHODS: Lumican- and fibromodulin-null heterozygous mice were intercrossed to obtain wild-type (Lum(+/+)Fmod(+/+)), lumican-null (Lum(-/-)Fmod(+/+)), fibromodulin-null (Lum(+/+)Fmod(-/-)), and double-null (Lum(-/-)Fmod(-/-)) littermates. Axial length was measured on enucleated whole eyes, and ocular structural changes were examined by histology. The morphology of collagen fibrils in the sclera was examined by transmission electron microscopy (TEM). RESULTS: Compared with the ocular axial length in wild type mice, the axial length was increased by 10% in Lum(-/-)Fmod(-/-) (P = 0.02) mice. Retinal detachment was frequent in the double-null and rare in the lumican-null animals. Compared with the wild-type sclera, the sclera in all null mutants was significantly thinner with fewer lamellae (P &lt; 0.05). The double-null sclera contained abnormally large-diameter (120-160 nm) and small-diameter (30-60 nm) collagen fibrils, whereas the fibromodulin-null sclera was enriched for the small-diameter fibrils. The collagen fibril diameter distribution in the lumican-null sclera was similar to that of the wild-type. CONCLUSIONS: An increase in small-diameter fibrils in the fibromodulin-null sclera suggests a key role for fibromodulin in the maturation and assembly of scleral collagen fibrils. That fibril diameter distribution in the lumican-null sclera was comparable to that in the wild type, but severely disrupted in the double null, suggests a role for lumican that is crucial in the absence of fibromodulin. The eyes of Lum(-/-)Fmod(-/-) mice show certain features of high myopia: increased axial length, thin sclera, and retinal detachment. Mutations or altered expression of these proteoglycans may contribute to myopia in humans.},
  author       = {Chakravarti, Shukti and Paul, Jennifer and Roberts, Luke and Chervoneva, Inna and Oldberg, Åke and Birk, David E},
  issn         = {1552-5783},
  language     = {eng},
  number       = {6},
  pages        = {2422--2432},
  publisher    = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
  series       = {Investigative Ophthalmology & Visual Science},
  title        = {Ocular and scleral alterations in gene-targeted lumican-fibromodulin double-null mice.},
  url          = {http://dx.doi.org/},
  volume       = {44},
  year         = {2003},
}