May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Laminin Ablation From ILM Induces Progressive Retinal Ganglion Cell Loss and Abnormal Axonal Trajectories
Author Affiliations & Notes
  • G. A. Pinzon-Duarte
    Anatomy Cell Biology & Ophthalmology, SUNY Downstate Medical Center, Brooklyn, New York
  • Y. Li
    Anatomy Cell Biology & Ophthalmology, SUNY Downstate Medical Center, Brooklyn, New York
  • A. Kuver
    Anatomy Cell Biology & Ophthalmology, SUNY Downstate Medical Center, Brooklyn, New York
  • W. J. Brunken
    Anatomy Cell Biology & Ophthalmology, SUNY Downstate Medical Center, Brooklyn, New York
  • Footnotes
    Commercial Relationships  G.A. Pinzon-Duarte, None; Y. Li, None; A. Kuver, None; W.J. Brunken, None.
  • Footnotes
    Support  NIH Grant EY12676; NSF IBN-0637038
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5903. doi:https://doi.org/
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    • Get Citation

      G. A. Pinzon-Duarte, Y. Li, A. Kuver, W. J. Brunken; Laminin Ablation From ILM Induces Progressive Retinal Ganglion Cell Loss and Abnormal Axonal Trajectories. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5903. doi: https://doi.org/.

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

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Abstract

Purpose: : Genetic ablation of both β2 and γ3 chains of laminin leads to the disruption of the inner limiting membrane (ILM) causing a retinal dysplasia. Because retinal ganglion cell (RGC) development and survival are associated with the integrity of this membrane, we examine how disruptions in laminin expression affects RGC development, distribution and axonal targeting.

Methods: : Retinas from wild type (WT), β2-/-, γ3-/- and β2-/-:γ3-/- mice were collected during postnatal development from P0 to 15 were examined by conventional microscopy, immunohistochemistry and electron microscopy. The following markers were used: Brn-3a and DiI for RGCs; Tuj-1 for ganglion cell axons; collagen IV, nidogen and perlecan for the ILM.

Results: : In whole mounted WT retinas, the ILM was continuous and the Müller cell endfoot ended in a regular array encasing the cells in the RGC layer. Brn-3a or DiI labeled RGCs were evenly spaced throughout the RGC layer. In γ3-/- retina, the ILM, RGCs and Müller cells were unaffected. Ganglion cell axons trajectory and targeting was normal. In the β2-/- mouse there were some disruptions in ILM, and RGCs distribution. In the β2-/-:γ3-/- compound null the ILM was discontinuous and Müller cell endfeet were in disarray. The RGCs distribution, and axonal trajectories, and targeting were disrupted. Specifically, the cell density varied regionally_ i.e., regions of normally distributed cells alternated with regions of clustered cells or regions nearly devoid of labeled RGCs. Labeled RGCs were spatially restricted to those regions in which the ILM was undisturbed. At PO, the axon targeting and trajectories to the head of the optic nerve are normal. However, by P15 axon trajectories become tortuous and frequent de-fasciculations are seen. The targeting of axons to the head of the optic nerve is normal. The disruption of the axonal trajectories parallels the development of abnormal retinal vessels suggesting a physical disruption of the RGC axons occurs. At P15, the optic nerves of these animals are hypoplastic; we are studying the progressive degeneration in the RGC layer.

Conclusions: : Our hypothesis is that RGC and Müller cells adhere to the ILM; the absence of the ILM in the mutant animal causes a progressive loss of RGCs and concomitantly a disruption in axonal organization. These studies suggest that RGCs rely on contact with the ILM, thus there may be implications in the surgical stripping of the ILM used in the treatment of human ocular pathologies.

Keywords: ganglion cells • extracellular matrix • optic nerve 
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