September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Dystroglycan regulates retinal development
Author Affiliations & Notes
  • Reena Clements
    Vollum Institute, Oregon Health and Science University, Portland, Oregon, United States
  • Kevin M Wright
    Vollum Institute, Oregon Health and Science University, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Reena Clements, None; Kevin Wright, None
  • Footnotes
    Support  NSF GRFP DGE 1448072, MRF 215 Wright
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1768. doi:
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    • Get Citation

      Reena Clements, Kevin M Wright; Dystroglycan regulates retinal development. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1768.

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

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Abstract

Purpose : The molecular basis for visual system defects observed in human patients with dystroglycanopathy is largely unknown. We have established a role for dystroglycan in maintenance of the retinal inner limiting membrane (ILM) over development. The ILM provides critical cues that direct retinal development, and in its absence, numerous defects arise. This study utilizes mouse models to study the role of dystroglycan in regulating cell migration, axon guidance, and circuit formation during retinal development.

Methods : Mice with a mutation in isoprenoid synthase domain (ISPDL79*) were utilized as a model of severe dystroglycanopathy over embryonic development, and mice in which dystroglycan is conditionally deleted in the visual system (DGF/-; Six3cre) were utilized to study postnatal development. Migration, axon guidance, and dendritic arborization were assessed using cryosections and flat mount retina preparations.

Results : Dystroglycan is required for retinal development and circuit formation. ISPDL79* and DGF/-; Six3cre mutants exhibit progressive neuronal migration and axon guidance defects. Studies at single cell resolution show that there are an increased proportion of retinal ganglion cells (RGCs) in mutants exhibiting aberrant cellular morphologies that include inappropriate axon extension. We find that many cell types, including RGCs and amacrine cells, are found in ectopic cellular clusters within the vitreous space. Furthermore, dendritic stratification and mosaic spacing of cells is abnormal in the absence of functional dystroglycan.

Conclusions : Our study utilizes genetic models to demonstrate a critical role for dystroglycan in the multiple aspects of retinal development.

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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