Latent TGF-{beta} binding protein-2 is essential for the development of ciliary zonule microfibrils

In this study, we explore the in vivo function of LTBP-2 by generating Ltbp2–/– mice. Ltbp2–/– mice survived to adulthood but developed lens luxation caused by compromised ciliary zonule formation without a typical phenotype related to glaucoma, suggesting that LTBP-2 deficiency primarily causes lens dislocation but not glaucoma. The suppression of LTBP2 expression in cultured human ciliary epithelial cells by siRNA disrupted the formation of the microfibril meshwork by the cells. Supplementation of recombinant LTBP-2 in culture medium not only rescued the microfibril meshwork formation in LTBP2-suppressed ciliary epithelial cells but also restored unfragmented and bundled ciliary zonules in Ltbp2–/– mouse eyes under organ culture. Although several reported human mutant LTBP-2 proteins retain normal domain structure and keep the fibrillin-1-binding site intact, none of these mutant proteins were secreted from their producing cells, suggesting secretion arrest occurred to the LTBP-2 mutants owing to conformational alteration. The findings of this study suggest that LTBP-2 is an essential component for the formation of microfibril bundles in ciliary zonules.

Source: Human Molecular Genetics - October 8, 2014 Category: Genetics & Stem Cells Authors: Inoue, T., Ohbayashi, T., Fujikawa, Y., Yoshida, H., Akama, T. O., Noda, K., Horiguchi, M., Kameyama, K., Hata, Y., Takahashi, K., Kusumoto, K., Nakamura, T. Tags: ARTICLES Source Type: research