September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The role of dystrophin isoforms in retinal development and vaso-proliferative disease
Author Affiliations & Notes
  • Mollie Friedlander
    School of Medicine, Stanford University, Stanford, California, United States
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Felicitas Bucher
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Peter D Westenskow
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Edith Aguilar
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Stacey K Moreno
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Tim U Krohne
    University of Bonn, Bonn, Germany
  • Yoshihiko Usui
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Toshihide Kurihara
    Keio University, Tokyo, Japan
  • Lea Scheppke
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Martin Friedlander
    Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Mollie Friedlander, None; Felicitas Bucher, None; Peter Westenskow, None; Edith Aguilar, None; Stacey Moreno, None; Tim Krohne, None; Yoshihiko Usui, None; Toshihide Kurihara, None; Lea Scheppke, None; Martin Friedlander, None
  • Footnotes
    Support  NIH Grant EY11254
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4533. doi:
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    • Get Citation

      Mollie Friedlander, Felicitas Bucher, Peter D Westenskow, Edith Aguilar, Stacey K Moreno, Tim U Krohne, Yoshihiko Usui, Toshihide Kurihara, Lea Scheppke, Martin Friedlander; The role of dystrophin isoforms in retinal development and vaso-proliferative disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4533.

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

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Abstract

Purpose : Dystrophin defects have been associated with vascular abnormalities in muscular tissue, the heart and the central nervous system. While most organs strongly express one dystrophin isoform, the retina expresses at least four different dystrophin isoforms including Dp427, Dp260, Dp140 and Dp71. In the retina, the short isoform Dp71 has been associated with angiogenesis and vascular homeostasis. The potential contribution of other dystrophin isoforms to retinal angiogenesis is poorly understood. In this study, we investigated the expression and potential influence of dystrophin isoforms on retinal angiogenesis during physiologic development and under hypoxic stress.

Methods : qPCR, western blot and in situ analysis were used to characterize expression patterns of dystrophin isoforms during physiologic retinal development. Retinal angiogenesis during physiologic development and in the mouse model of oxygen-induced retinopathy (OIR) was compared in transgenic mouse models that lacked Dp427 (mdx), Dp427 and Dp260 (mdx-4cv) or all dystrophin isoforms (mdx-3cv). In OIR, pups of all strains were exposed to 75% oxygen from postnatal day 7 (P7) to P12 and then returned to normoxia to induce hypoxic stress. Vascular changes were measured by quantification of the areas of neovascularization and vaso-obliteration at P17.

Results : During physiologic retinal development, expression of the dystrophin isoforms Dp427 and Dp260 were significantly increased following P7, while expression levels of the short isoform Dp71 remained constant. In situ hybridization analysis detected Dp427 at the inner and outer nuclear layer as well as the nerve fiber layer of the retina. While no gross changes in the development of the superficial vascular plexus were detected in any of the three transgenic mouse models, mdx mice developed a 20% increase in pre-retinal neovascularization in the OIR model relative to littermate controls (N=9-13, P<0.05).

Conclusions : The retina regulates the expression of multiple dystrophin isoforms during physiologic development. Expression of Dp427 in the nerve fiber layer close to the primary vascular plexus suggests that Dp427 might be involved in retinal vascular homeostasis. Through the comparison of three transgenic mouse models that lack distinct dystrophin isoforms, we were able to identify Dp427 as a potential mediator of retinal vascular angiogenesis under conditions of hypoxic stress.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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