April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
In vivo Location-dependent Differential Vulnerability of Rabbit RGCs to Excitotoxicity
Author Affiliations & Notes
  • Cun-Jian Dong
    Biological Sciences, Allergan Inc, Irvine, California
  • Yuanxing Guo
    Biological Sciences, Allergan Inc, Irvine, California
  • Agey Peter
    Biological Sciences, Allergan Inc, Irvine, California
  • William A. Hare
    Biological Sciences, Allergan Inc, Irvine, California
  • Footnotes
    Commercial Relationships  Cun-Jian Dong, Allergan Inc (E); Yuanxing Guo, Allergan Inc (E); Agey Peter, Allergan Inc (E); William A. Hare, Allergan Inc (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3095. doi:https://doi.org/
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      Cun-Jian Dong, Yuanxing Guo, Agey Peter, William A. Hare; In vivo Location-dependent Differential Vulnerability of Rabbit RGCs to Excitotoxicity. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3095. doi: https://doi.org/.

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

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Abstract

Purpose: : Progressive loss from peripheral to central visual field is a common finding in glaucoma. It has been proposed that higher sensitivity of the peripheral field to glaucomatous loss results from lower numbers of RGCs sampling the same patch of visual space (lower redundancy). Here, we have explored location-dependent sensitivity of RGCs to excitotoxic injury, a significant contributor to RGC loss in different models of experimental glaucoma.

Methods: : We used patch clamp and Ca++ imaging of in situ RGCs to characterize various tool compounds that protect RGCs in experimental glaucoma as well as NMDA-induced excitotoxicity models and used the latter to also determine the regional dependence of RGC sensitivity to excitotoxicity. RGC injury was evaluated by counting dye labeled cells in the ganglion cell layer at the visual streak (VS) and more peripheral regions in the inferior retina. RGC numbers were estimated by subtracting displaced starburst amacrine cells (dsACs) from the total cell count.

Results: : In normal rabbits, RGC density is highest at the VS with 167 cells/field (48,400 µ2). RGC density decreases to 28 cells/field at 5mm inferior to the VS. However, the density of dsACs shows a lesser decrease, from 31 cells/field to 16 cells/field, over the same 5mm retinal distance. Intravitreal injection of 3.6 µmol of NMDA resulted in an overall 56% loss of RGCs (average of 6 rabbits) at two weeks following injection but had no effect on counts of dsACs. Detailed analysis reveals that RGC sensitivity to NMDA toxicity increases with distance from the VS: 45% loss at the VS and 58, 66, 80, and 85% loss seen at 1.25, 2.5, 3.75, and 5 mm away from the VS inferiorly. We found that five classes of compounds that protect RGCs through different mechanisms of action in experimental glaucoma also protect RGCs from NMDA-induced injury. These results support the notion that excitotoxicity is a major contributor to RGC loss in experimental glaucoma.

Conclusions: : Our results confirm mechanistically the link between excitotoxicity and RGC loss in experimental glaucoma and show a selective vulnerability of RGC over dsACs to excitotoxicity. They also demonstrate for the first time a greater sensitivity of peripheral RGCs to excitotoxicity that could contribute to the clinical finding that central visual field is most resistant to glaucomatous vision loss.

Keywords: ganglion cells • visual fields • inner retina dysfunction: biochemistry and cell biology 
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