Biological function of matrix protein LTBP-2 and its involvement in eye diseases

• Project/Area Number: 25462741
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kansai Medical University
• Principal Investigator: AKAMA Tomoya 関西医科大学, 医学部, 准教授 (10548788)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 細胞外マトリックス構築 / ミクロフィブリル / 遺伝子改変動物 / 遺伝病 / 疾患モデル動物 / 細胞外マトリックス / 緑内障 / 水晶体脱臼 / 毛様小帯 / 毛様小体

Outline of Final Research Achievements

Using gene knockout mice, we studied biological function of latent TGR-beta binding protein-2 (LTBP-2) and found the mutant mice develop lens dislocation due to malformation of ciliary zonules, which anchors lens to ciliary bodies in the eye. Since mutations of LTBP2, a gene encoding LTBP-2, have been found on patients of inherited eye diseases, such as primary congenital glaucoma and ectopia lentis, we analyzed any phenotypes related to glaucoma in the mutant mice. We observed LTBP-2-deficent DBA2 mice show higher intraocular pressure compared to wild type mice, but this phenotype was not observed in B6 strain. These results indicated that LTBP-2 deficient mice will be one of the model animals for analysis of human ocular diseases.

Research Products

• [Journal Article] Latent TGFβ binding protein-2 is essential for the development of ciliary zonule microfibrils. (2014)
  • Author(s): Inoue T., Ohbayashi T., Fujikawa Y., Yoshida H., Akama T.O., Noda K., Horiguchi M., Kameyama K., Hata Y., Takahashi K., Kusumoto K. and Nakamura T.
  • Journal Title: Human Molecular Genetics Volume: 23 Issue: 21 Pages: 5672-5682
  • DOI: 10.1093/hmg/ddu283
  • Peer Reviewed / Open Access
• [Journal Article] Latent TGF-beta binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. (2013)
  • Author(s): Noda K., Dabovic B., Takagi K., Inoue T., Horiguchi M., Hirai M., Fujikawa Y., Akama T. O., Kusumoto K., Zilberberg L., Sakai L. Y., Koli K., Naitoh M., von Melchner H., Suzuki S., Rifkin D. B., Nakamura T
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 110 Issue: 8 Pages: 2852-2857
  • DOI: 10.1073/pnas.1215779110
  • Peer Reviewed
• [Presentation] Mutant LTBP-2 proteins lack secretion ability and fibrillin-1 binding ability. (2013)
  • Author(s): Akama, T.O., Fujikawa, Y., Inoue, T., Nakamura, T.
  • Organizer: Annual meeting of Association for Research in Vision and Ophthalmology
  • Place of Presentation: Seattle, WA, USA