April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Src Inhibition Reduces Neurodegeneration in a Mouse Model of Penetrating Posterior Ocular Trauma
Author Affiliations & Notes
  • M. J. Allingham
    University of North Carolina, Chapel Hill, North Carolina
  • G. Malek
    Duke University Eye Center, Durham, North Carolina
  • P. Saloupis
    Duke University Eye Center, Durham, North Carolina
  • S. W. Cousins
    Duke University Eye Center, Durham, North Carolina
  • Footnotes
    Commercial Relationships  M.J. Allingham, None; G. Malek, None; P. Saloupis, None; S.W. Cousins, None.
  • Footnotes
    Support  NEI 13818
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4157. doi:
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      M. J. Allingham, G. Malek, P. Saloupis, S. W. Cousins; Src Inhibition Reduces Neurodegeneration in a Mouse Model of Penetrating Posterior Ocular Trauma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4157.

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

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Purpose: : Combat ocular trauma resulting in retinal detachment, vitreous and choroidal hemorrhage or retinal vascular injury is one of the most common battlefield injuries among United States soldiers. Of note, a substantial fraction of these patients have poor visual outcome despite surgical intervention resulting in adequate anatomical repair. We hypothesized that low grade, chronic inflammation resulting in neurodegenerative changes in the retina contribute to poor visual outcomes in anatomically repaired eyes. It has previously been shown that Src family tyrosine kinases play a role in several steps of the inflammatory response from leukocyte diapedesis to monocyte production of TNFalpha. Accordingly, we tested the hypothesis that Src inhibition would reduce retinal inflammation and neurodegeneration in a mouse model of penetrating posterior ocular trauma (PPOT).

Methods: : We used a mouse model of PPOT to simulate penetrating ocular injury. In our model, both the site of penetrating injury as well as the retinal detachment resolve spontaneously within 7 days. This simulates surgical repair in humans. To test the role of Src in inflammation and neurodegeneration after PPOT, we intraperitonealy administered PP2 (3 mg/kg), a specific inhibitor of Src family kinases, or vehicle control in our mouse model. Eyes were harvested after 7 days. Retinas were removed from some eyes for western blot to quantify active Src . Other eyes were cryopreserved and 10 micron cryosections were examined immunohistologically for macrophage infiltration, reactive gliosis, and synaptic degeneration.

Results: : We found that retinal levels of active Src were increased after PPOT and that this was inhibited by administration of PP2. PP2 did not affect the number of monocytes recruited to injured eyes. However, we did observe a reduction in both reactive gliosis and synaptic degeneration in mice treated with PP2.

Conclusions: : These observations suggest that Src may not be required for monocyte recruitment in our model, but that it may play a role in mediating the neurodegenerative and wound healing responses in the retina following PPOT.

Keywords: retina • trauma • neuroprotection 

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