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

Research output: Contribution to journalArticle

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 < 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.

Details

Authors
  • Shukti Chakravarti
  • Jennifer Paul
  • Luke Roberts
  • Inna Chervoneva
  • Åke Oldberg
  • David E Birk
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Ophthalmology
Original languageEnglish
Pages (from-to)2422-2432
JournalInvestigative Ophthalmology & Visual Science
Volume44
Issue number6
Publication statusPublished - 2003
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Cell and Matrix Biology (LUR000002), Åke Oldberg´s group (013212049)