July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Receptor for advanced glycation end product (RAGE) mediates retinal ganglion cell loss in experimental glaucoma
Author Affiliations & Notes
  • Nafiseh Alsadat Seyed Hosseini Fin
    Department of Orthoptics, University of Technology, Sydney, Sydney, New South Wales, Australia
  • Maria Sukkar
    Graduate School of Health, University of Technology, Sydney, Sydney, New South Wales, Australia
  • Mojtaba Golzan
    Department of Orthoptics, University of Technology, Sydney, Sydney, New South Wales, Australia
  • Footnotes
    Commercial Relationships   Nafiseh Alsadat Seyed Hosseini Fin, None; Maria Sukkar, None; Mojtaba Golzan, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3726. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Nafiseh Alsadat Seyed Hosseini Fin, Maria Sukkar, Mojtaba Golzan; Receptor for advanced glycation end product (RAGE) mediates retinal ganglion cell loss in experimental glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3726.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Glaucoma is associated with an increase in intraocular pressure (IOP) and subsequent retinal ganglion cell (RGC) loss. There is evidence that the receptor for advanced glycation end product (RAGE) and its ligand, beta amyloid (Aβ), are highly expressed in RGCs of glaucomatous eyes. In this study, we investigated if RAGE-deficient mice are protected against RGC loss.

Methods : Acute ocular hypertension (AOH) was induced in one eye of RAGE-/- and wild type (WT) mice using an elevated reservoir of sterile balanced salt solution. Pressure was raised to 90 mmHg and maintained for 45 minutes. The fellow eye was injected but not pressurized, acting as a control. At seven days’ post AOH, animals were euthanized and tissues collected. Baseline and terminal optical coherence tomography (OCT) was also performed. RGC count at the optic nerve head, retinal morphology and total RGC loss was quantified using Haemotoxylin and Eosin staining, OCT analysis and western blotting for Brn3a, a RGC specific marker.

Results : In WT and RAGE-/- mice, AOH induced a 36% (n=4, p<0001) and 18% (n=4, p=0.001) loss in RGC, relative to the control eye, respectively. While AOH induced RGC loss in both RAGE-/-and WT mice, however, there was significantly more RGC loss in WT compared to RAGE-/- mice (p<0.0001). Consistent with this, OCT in vivo imaging showed that AOH reduced RGC layer and total retinal thickness by 26% (n=4, p=0.05) and 10% (n=4, p=0.007) in WT mice, respectively. In contrast, AOH did not significantly reduce RGC layer and total retinal thickness in RAGE-/- mice (15% and 5%, n=4, p>0.05). In WT mice, compared to the control eye, AOH reduced Brn3a protein expression by 71% (n=3, p=0.04). In RAGE-/- mice, compared to the control eye, Brn3a protein expression was reduced by 21% but this was not statistically significant (n=3, p>0.05). Moreover, Brn3a protein expression following AOH in WT mice was 70% less than that following AOH in RAGE-/- mice (n=3, p=0.002).

Conclusions : In this study, we observed significantly less RGC loss in RAGE deficient mice following AOH, suggesting RAGE may play a pivotal role in glaucoma pathogenies. The exact mechanism in which RAGE mediates RGC loss in glaucoma is still unclear. We are currently investigating if RAGE orchestrates Aβ influx into RGCs via endocytosis, leading to cell death.

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

 

 

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×