June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
The Role of Annexin A4 in Stabilizing Cell Membranes Undergoing Biomechanical Stress Relevant to Glaucoma
Author Affiliations & Notes
  • Nevena Vicic
    Ophthalmology and Vision Science, University of Toronto, Toronto, ON, Canada
    Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  • Cindy Guo
    Ophthalmology and Vision Science, University of Toronto, Toronto, ON, Canada
    Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
  • John G. Flanagan
    Ophthalmology and Vision Science, University of Toronto, Toronto, ON, Canada
    School of Optometry, University of California, Berkeley, Berkeley, CA
  • Jeremy M Sivak
    Ophthalmology and Vision Science, University of Toronto, Toronto, ON, Canada
    Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
  • Footnotes
    Commercial Relationships Nevena Vicic, None; Cindy Guo, None; John Flanagan, None; Jeremy Sivak, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2440. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Nevena Vicic, Cindy Guo, John G. Flanagan, Jeremy M Sivak; The Role of Annexin A4 in Stabilizing Cell Membranes Undergoing Biomechanical Stress Relevant to Glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2440.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: The mechanotransduction mechanisms by which inner retinal cells respond to biomechanical stress in glaucoma are not well understood. We have previously shown that annexin A4 (ANXA4), a calcium-dependent membrane binding protein, is significantly upregulated in an in vitro biomechanical insult model. Here, we determine ANXA4 expression and localization in the retina in vivo, and test its potential protective role in membrane stabilization in response to biomechanical strain in vitro.

Methods: Immunofluorescence microscopy was used to identify the pattern of ANXA4 protein in mouse, rat, and human retinas. Acute biomechanical and ischemic stress was induced in rodent retinas in vivo, and in primary rodent retinal astrocytes in vitro. ANXA4 localization and expression was examined using fluorescence imaging and quantitative RT-PCR, respectively. Fluorescence imaging of an astrocytic cell line transiently transfected with GFP-tagged ANXA4 was used to visualize its localization and membrane dynamics in response to elevated intracellular calcium.

Results: ANXA4 antibody staining revealed conserved localization to the ganglion cell layer and optic nerve head (ONH) in healthy mouse, rat, and human retinas. Furthermore, there was a 6-fold increase in ANXA4 expression by 18 hours following elevation of intraocular pressure in vivo (p=0.039). Imaging of primary retinal astrocytes showed evidence of ANXA4 localization to cellular and nuclear membranes upon application of biomechanical stress. Furthermore, ANXA4 dramatically reduced membrane blebbing upon rapid elevation of intracellular calcium.

Conclusions: ANXA4 was localized to the cells lining the inner retina and ONH, and responded to calcium and biomechanical strain relevant to glaucoma. Results suggest that when translocated to the membrane, ANXA4 can increase membrane stability to improve cell survival under conditions of biomechanical strain.

×
×

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.

×