July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Reversibility of retinal ganglion cell dysfunction due to chronic IOP elevation.
Author Affiliations & Notes
  • Da Zhao
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Vickie Hoi Ying Wong
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Zheng He
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Christine Tram Oanh Nguyen
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Andrew Ian Jobling
    Anatomy & Neuroscience , University of Melbourne, Melbourne, Victoria, Australia
  • Erica Fletcher
    Anatomy & Neuroscience , University of Melbourne, Melbourne, Victoria, Australia
  • Holly Chinnery
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Patricia Jusuf
    BioSciences, University of Melbourne, Melbourne, Victoria, Australia
  • Jeremiah K.H. Lim
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Algis J Vingrys
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Bang V Bui
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Da Zhao, None; Vickie Wong, None; Zheng He, None; Christine Nguyen, None; Andrew Jobling, None; Erica Fletcher, None; Holly Chinnery, None; Patricia Jusuf, None; Jeremiah Lim, None; Algis Vingrys, None; Bang Bui, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3696. doi:
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    • Get Citation

      Da Zhao, Vickie Hoi Ying Wong, Zheng He, Christine Tram Oanh Nguyen, Andrew Ian Jobling, Erica Fletcher, Holly Chinnery, Patricia Jusuf, Jeremiah K.H. Lim, Algis J Vingrys, Bang V Bui; Reversibility of retinal ganglion cell dysfunction due to chronic IOP elevation.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3696.

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

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Abstract

Purpose : To determine the duration of chronic IOP elevation beyond which ganglion cell function can no longer recover using the mouse circumlimbal suture model.

Methods : IOP elevation was induced in anaesthetized (isoflurane) adult male C57BL6/J mice by attaching a circumlimbal suture (nylon, 10/0) around the equator of one eye, with the contralateral eye serving as a control. The suture was left in place for 8, 12 and 16 weeks (n=27, 23 and 27), respectively, and animals underwent electroretinography and optical coherence tomography at these time points. In two other groups, the suture was removed after 8 and 12 weeks (n=26 and 28), and the capacity for recovery assessed 4 weeks later. IOP was measured weekly (Tonolab). Retinal ganglion cell (RGC) function (or integrity) was assessed with the positive scotopic threshold response (pSTR) and retinal nerve fibre layer (RNFL) thickness. Data (mean ± SEM) were compared using t-test (control vs. treatment) and one-way ANOVA (within groups).

Results : IOP in sutured eyes was higher than control eyes (8wk: 17.1 ± 0.3 vs. 26.8 ± 0.6 mmHg, 12wk: 13.8 ± 0.3 vs. 19.5 ± 0.5 mmHg, 16wk: 17.1 ± 0.2 vs. 27.4 ± 0.6 mmHg; all P<0.001). After suture removal, IOP returned to levels comparable to control eyes (8+4wk: 16.9 ± 0.3 vs. 16.1 ± 0.3 mmHg; P=0.08, 12+4wk: 17.3 ± 0.2 vs. 17.1 ± 0.3 mmHg; P=0.5). With IOP elevation, RGC function declined to 75% ± 8% (8wk), 78% ± 7% (12wk) and 59% ± 4% (16wk, all P<0.001) of control eyes. RNFL thinning was also evident (8wk: 84% ± 4%, 12wk: 83% ± 5%; 16wk: 83% ± 3%; P<0.001) but no change in total retinal thickness was noted (P=0.33). Suture removal at week 8 facilitated full recovery of RGC function (97% ± 7%, P=0.9 vs. baseline) 4 weeks later. However, there was no recovery in RNFL thickness (87% ± 3%, P<0.001 vs. baseline). When the suture was removed at week 12, neither function (79% ± 9%, P<0.05) nor RNFL thickness recovered (89% ± 3%, P<0.01) 4 weeks later.

Conclusions : RGC dysfunction can be recovered 4 weeks after an 8-week period of mild IOP elevation, but not after a 12-week period. Beyond 12 weeks, IOP reversal only served to prevent further functional decline. This identifies a critical chronic IOP duration that results in irreversible ganglion cell dysfunction.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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