June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Necroptosis is responsible for RGC but not photoreceptor degeneration after blunt ocular trauma.
Author Affiliations & Notes
  • Chloe Naomi Thomas
    Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, United Kingdom
  • Adam Thompson
    Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, United Kingdom
  • Ann Logan
    Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, United Kingdom
    University Hospitals Birmingham, NIHR Surgical Reconstruction and Microbiology Centre, Birmingham, United Kingdom
  • Richard J Blanch
    Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, United Kingdom
    University Hospitals Birmingham, NIHR Surgical Reconstruction and Microbiology Centre, Birmingham, United Kingdom
  • Zubair Ahmed
    Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, United Kingdom
  • Footnotes
    Commercial Relationships   Chloe Thomas, None; Adam Thompson, None; Ann Logan, None; Richard Blanch, None; Zubair Ahmed, None
  • Footnotes
    Support  Fight for Sight PhD Studentship (Grant code: 1560/1561)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1759. doi:
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    • Get Citation

      Chloe Naomi Thomas, Adam Thompson, Ann Logan, Richard J Blanch, Zubair Ahmed; Necroptosis is responsible for RGC but not photoreceptor degeneration after blunt ocular trauma.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1759.

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

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Abstract

Purpose : Blunt ocular trauma causes commotio retinae and traumatic optic neuropathy (TON), characterised by photoreceptor and retinal ganglion cell (RGC) degeneration, respectively. Photoreceptor and RGC death occurs at and around the injury site, contributing to potentially irreversible visual loss. TON can be direct, where the optic nerve is crushed or cut, or more commonly indirect, where brain or ocular injury is associated with secondary RGC degeneration.
Receptor interacting protein-1 (RIP-1) is a cell death protein associated with regulated necrosis, termed necroptosis. We hypothesised that RIP-1 contributes to retinal degeneration after blunt ocular trauma and its inhibition would reduce retinal cell death.

Methods : Anaesthetised adult Lister hooded rats were subjected to bilateral ballistic ocular trauma. RIP-1 expression was assessed by western blots in whole retinal lysate at 5, 24 and 48 hours after injury. RIP-1 activity was inhibited by unilateral intravitreal injection of Necrostatin-1 at 0 and 7 days post injury, with contralateral PBS control. Animals were euthanized at 14 days and RGC survival assessed by Brn3a and RBPMS counts and photoreceptor survival by outer nuclear layer (ONL) thickness, on sagittal retinal sections.

Results : Retinal full-length RIP-1 protein expression increased at 48 hours after injury (ANOVA; p<0.01, post-hoc Tukey; p<0.01). RIP-1 inhibition by intravitreal injection of Necrostatin-1 protected RGC [Brn3a (GEE; p<0.01) and RBPMS (GEE; p<0.05) counts], at the centre of the injury site (student t-test p<0.01), but did not affect ONL thickness (GEE; p>0.05), compared to PBS control.

Conclusions : RIP-1 mediates a proportion of RGC death in blunt ocular trauma towards the centre of the injury site, but does not mediate photoreceptor degeneration.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

 

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