Regular Article
Smad Translocation and Growth Suppression in Lens Epithelial Cells by Endogenous TGFβ2 during Wound Repair

https://doi.org/10.1006/exer.2001.1002Get rights and content

Abstract

To determine whether endogenous TGFβ affects lens epithelial cells during repair after an anterior capsule injury in mice, we studied translocation of Smad proteins, which carry the TGFβ signal from cell surface receptors to promoters in nuclei. We immunolocalized Smads in murine lenses at intervals up to 8 weeks following capsular injury. Effects of injecting TGFβ neutralizing antibodies on Smad4 location and cell proliferation were examined at 24 hr after injury. Finally, we examined whether exogenous TGFβ2 induced Smad nuclear translocation in murine lenses in organ culture. Cell proliferation was quantitated by 5-bromo-2′-deoxyuridine (BrdU) labelling. In uninjured lenses, Smads were located in the cytoplasm. In injured lenses, nuclear localization of Smads was observed in cells next to the capsular break from 8 to 24 hr after the injury, and was observed peripheral to the break at 48 hr. Nuclear Smads then continued to be observed occasionally in a minority of cells. Injection of antibodies neutralizing TGFβ2, but not TGFβ1 or TGFβ3, inhibited Smad4 nuclear translocation and resulted in the appearance of BrdU-positive anterior epithelial cells. With the lenses in culture, transient nuclear localization of Smads occurred between 3 and 24 hr in response to continuous exposure to TGFβ2. No nuclear translocation was seen at 48 hr. Endogenous TGFβ2 affects lens cells during wound repair after anterior capsule injury, inhibiting lens cell proliferation during the early phase. Nuclear translocation of Smads in lens epithelial cells is transient even with continuous exposure to TGFβ2.

References (27)

  • A. Weinsieder et al.

    Aqueous humor in lens repair and cell proliferation

    Exp. Eye Res.

    (1976)
  • S.W. Cousins et al.

    Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor

    Invest. Ophthalmol. Vis. Sci.

    (1991)
  • C. Gordon-Thomson et al.

    Differential cataractogenic potency of TGF-β1, -β2, and -β3 and their expression in the postnatal rat eye

    Invest. Ophthalmol. Vis. Sci.

    (1998)
  • Cited by (0)

    f1

    Address correspondence to: Shizuya Saika, Department of Ophthalmology, Wakayama Medical College, 811-1 Kimiidera, Wakayama, 641-0012, Japan. E-mail: [email protected]

    View full text