Special Issue Research Article
Collagen fibril assembly during postnatal development and dysfunctional regulation in the lumican-deficient murine cornea
Article first published online: 19 JUN 2006
Copyright © 2006 Wiley-Liss, Inc.
Special Issue: Mouse Development Special Issue
Volume 235, Issue 9, pages 2493–2506, September 2006
How to Cite
Chakravarti, S., Zhang, G., Chervoneva, I., Roberts, L. and Birk, D. E. (2006), Collagen fibril assembly during postnatal development and dysfunctional regulation in the lumican-deficient murine cornea. Dev. Dyn., 235: 2493–2506. doi: 10.1002/dvdy.20868
- Issue published online: 9 AUG 2006
- Article first published online: 19 JUN 2006
- Manuscript Accepted: 12 MAY 2006
- National Institutes of Health. Grant Numbers: EY05129, EY11654
- extracellular matrix;
The transparent cornea is the outer barrier of the eye and is its major refractive surface. Development of a functional cornea requires a postnatal maturation phase involving development, growth and organization of the stromal extracellular matrix. Lumican, a leucine-rich proteoglycan, is implicated in regulating assembly of collagen fibrils and the highly organized extracellular matrix essential for corneal transparency. We investigated the regulatory role(s) of lumican in fibril assembly during postnatal corneal development using wild type (Lum+/+) and lumican-null (Lum−/−) mice. In Lum+/+ mice, a regular architecture of small-diameter fibrils is achieved in the anterior stroma by postnatal day 10 (P10), while the posterior stroma takes longer to reach this developmental maturity. Thus, the anterior and the posterior stroma follow distinct developmental timelines and may be under different regulatory mechanisms. In Lum−/− mice, it is the posterior stroma where abnormal lateral associations of fibrils and thicker fibrils with irregular contours are evident as early as P10. In contrast, the anterior stroma is minimally perturbed by the absence of lumican. In Lum+/+ mice, lumican is expressed throughout the developing stroma at P10, with strong expression limited to the posterior stroma in the adult. Therefore, the posterior stroma, which is most vulnerable to lumican-deficiency, demonstrates an early developmental defect in fibril structure and architecture in the Lum−/− mouse. These defects underlie the reported increased light scattering and opacity detectable in the adult. Our findings emphasize the early regulation of collagen structure by lumican during postnatal development of the cornea. Developmental Dynamics 235:2493–2506, 2006. © 2006 Wiley-Liss, Inc.