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Shoujun Chen, Shukti Chakravarti, David Birk; Interclass Synergistic Effects of Small Leucine-Rich Proteoglycans in Regulating Collagen Fibrillogenesis During Corneal Development. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5255.
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© ARVO (1962-2015); The Authors (2016-present)
Small leucine-rich proteoglycans (SLRPs) are critical for the regulation of stromal fibrillogenesis and corneal transparency. Class I and II SLRPs are enriched in the corneal stroma. These two families bind to different sites on collagen fibrils. The purpose of this study is to investigate cooperative interclass interactions in the regulation of fibrillogenesis in corneal stromal assembly.
Compound Lum-/-/Bgn-/- mice were generated by cross-breeding the single null mice. All experiments conformed to the ARVO statement for the Use of Animals in Ophthalmic and Vision Research. Stromal fibrillogenesis in this mouse model was analyzed using in vivo confocal microscopy, immunohistochemistry, electron microscopy and molecular/biochemical approaches.
The phenotype of compound null mice was compared with wild type mice, Lum-/- mice, and Bgn-/- mice. The wild type mice and Bgn-/- mice were phenotypically normal. Lum-/- mice exhibited cloudy corneas, while the opacity in corneas of compound Lum-/-/Bgn-/- mice was significantly greater. Both anterior and posterior light scattering were significantly increased in compound Lum-/-/Bgn-/- mice compared to Lum-/- mice as demonstrated by in vivo confocal microscopy. Disorganized thinner lamellae were observed using electron microscopy in the compound null mice compared to Lum-/- mice. These disorganized lamellae contain disorganized collagen fibrils with increased numbers of irregular, large diameter fibrils. These irregular collagen fibrils are heterogeneous in contour. The disorganized collagen fibrils also were observed at P10 when both Lum-/- mice and compound null mice have similar diameter collagen fibrils. Immunoreactivities for lumican or biglycan were not detected in the corneas of compound Lum-/-/Bgn-/- mice as expected. The immuno-relativities of collagens I and V as well as other SLRPs including keratocan, fibromodulin and decorin were comparable between Lum-/- mice and compound null mice.
The data indicate biglycan and lumican have synergistic effects in regulating collagen fibrillogenesis during corneal stromal assembly. They demonstrate cooperative modulation of both linear and lateral fibril growth during early development and provide the foundation for the regular collagen fibril organization in corneal stroma associated with transparency.
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