Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8455344 | Matrix Biology | 2014 | 9 Pages |
Abstract
The corneal stroma is enriched in small leucine-rich proteoglycans (SLRPs), including both class I (decorin and biglycan) and class II (lumican, keratocan and fibromodulin). Transparency is dependent on the assembly and maintenance of a hierarchical stromal organization and SLRPs are critical regulatory molecules. We hypothesize that cooperative interclass SLRP interactions are involved in the regulation of stromal matrix assembly. We test this hypothesis using a compound Bgnâ/0/Lumâ/â mouse model and single Lumâ/â or Bgnâ/0 mouse models and wild type controls. SLRP expression was investigated using immuno-localization and immuno-blots. Structural relationships were defined using ultrastructural and morphometric approaches while transparency was analyzed using in vivo confocal microscopy. The compound Bgnâ/0/Lumâ/â corneas demonstrated gross opacity that was not seen in the Bgnâ/0 or wild type corneas and greater than that in the Lumâ/â mice. The Bgnâ/0/Lumâ/â corneas exhibited significantly increased opacity throughout the stroma compared to posterior opacity in the Lumâ/â and no opacity in Bgnâ/0 or wild type corneas. In the Bgnâ/0/Lumâ/â corneas there were abnormal lamellar and fibril structures consistent with the functional deficit in transparency. Lamellar structure was disrupted across the stroma with disorganized fibrils, and altered fibril packing. In addition, fibrils had larger and more heterogeneous diameters with an abnormal structure consistent with abnormal fibril growth. This was not observed in the Bgnâ/0 or wild type corneas and was restricted to the posterior stroma in Lumâ/â mice. The data demonstrate synergistic interclass regulatory interactions between lumican and biglycan. These interactions are involved in regulating both lamellar structure as well as collagen fibrillogenesis and therefore, corneal transparency.
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Authors
Shoujun Chen, Marian F. Young, Shukti Chakravarti, David E. Birk,