April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Deficiency In Tgf Beta Signaling Enhances Apoptosis Of Retinal Neurons During Development
Barbara M. Braunger; Stefan M. Pielmeier; Cora Demmer; Victoria Landstorfer; Daniela Kawall; Herbert Jaegle; Ernst R. Tamm
Author Affiliations & Notes
  • Barbara M. Braunger
    Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany
  • Stefan M. Pielmeier
    Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany
  • Cora Demmer
    Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany
  • Victoria Landstorfer
    Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany
  • Daniela Kawall
    Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany
  • Herbert Jaegle
    Department of Ophthalmology, University Clinic, Regensburg, Germany
  • Ernst R. Tamm
    Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany
  • Footnotes
    Commercial Relationships  Barbara M. Braunger, None; Stefan M. Pielmeier, None; Cora Demmer, None; Victoria Landstorfer, None; Daniela Kawall, None; Herbert Jaegle, None; Ernst R. Tamm, None
  • Footnotes
    Support  Supported by DFG, Research Unit FOR 1075
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5417. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      Deficiency In Tgf Beta Signaling Enhances Apoptosis Of Retinal Neurons During Development
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      Barbara M. Braunger, Stefan M. Pielmeier, Cora Demmer, Victoria Landstorfer, Daniela Kawall, Herbert Jaegle, Ernst R. Tamm; Deficiency In Tgf Beta Signaling Enhances Apoptosis Of Retinal Neurons During Development. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5417.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

      ×
    • Get Permissions
  • Supplements
Abstract

Purpose: : To investigate the role of TGF-beta signaling during ontogenetic cell death in the mouse retina. In the spinal cord, TGF-beta does promote neuronal survival and may have similar effects on neurons in the retina.

Methods: : Floxed TGFbr2 mice in which LoxP sites had been introduced in the coding sequences of the gene encoding for the type 2 TGF-beta receptor (TGFbr2) were crossed with alpha-Cre mice expressing Cre recombinase in retinal neurons under control of the alpha- enhancer of the Pax6 promoter. As control, floxed Smad7 mice were used, in which LoxP sites had been introduced in the coding sequences of Smad7, an endogenous inhibitor of TGF-beta signaling. Western Blot analysis and quantitative real-time PCR were performed to confirm the conditional knockout. Apoptotic cell death of retinal neurons was analyzed at embryonic days (E) 12.4, 14.5, 16.5 and at postnatal days (P) 4, 7, 9 by TUNEL labeling and an ELISA for free nucleosomes.

Results: : Western blot analysis for TGFR-2 and Smad7 confirmed the conditional knock out in the retina in both mouse lines. Immunohistochemistry of phosphorylated Smad2/3 (pSmad) showed immunoreactivity in nuclei of retinal ganglion cells in wild-type animals, indicating activated TGF-beta signaling, whereas TGFbr2flox/flox/alpha-Cre mice showed dramatically reduced immunoreactivity. TUNEL analysis showed significantly (p < 0.01 - 0.05) more TUNEL positive cells in the retina of TGFbr2flox/flox/alpha-Cre mice at each time point when compared to their wild-type littermates. The increase in cell death resulted in a significantly thinner inner nuclear layer in adult mice and significantly fewer axons (p < 0.01) in the optic nerve. Standard flash-ERG indicates functional changes. In contrast, Smad7flox/flox/alpha-Cre mice showed significantly (p < 0.01 - 0.02) less apoptotic cell death in the retina when compared to their wild-type littermates.

Conclusions: : TGF-beta signaling protects retinal neurons from apoptotic cell death during development and may have comparable effects following retinal injury in adult animals.

Keywords: retina • neuroprotection • retinal development 
© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept