April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Hyperglycemia is Neuroprotective in a Rat Model of Experimental Glaucoma
Author Affiliations & Notes
  • A. Ebneter
    Ophthalmic Research Laboratories, S Australian Institute of Ophthalmology, Adelaide, Australia
  • G. Chidlow
    Ophthalmic Research Laboratories, S Australian Institute of Ophthalmology, Adelaide, Australia
  • J. P. M. Wood
    Ophthalmic Research Laboratories, S Australian Institute of Ophthalmology, Adelaide, Australia
  • R. J. Casson
    Ophthalmic Research Laboratories, S Australian Institute of Ophthalmology, Adelaide, Australia
  • Footnotes
    Commercial Relationships  A. Ebneter, None; G. Chidlow, None; J.P.M. Wood, None; R.J. Casson, None.
  • Footnotes
    Support  Foundation OPOS, St.Gallen, Switzerland
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3193. doi:https://doi.org/
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      A. Ebneter, G. Chidlow, J. P. M. Wood, R. J. Casson; Hyperglycemia is Neuroprotective in a Rat Model of Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3193. doi: https://doi.org/.

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

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Abstract

Purpose: : It might be expected that diabetic microangiopathy would exacerbate glaucomatous optic neuropathy (GON); however, the preponderance of epidemiological evidence does not support this expectation. Indeed, the Ocular Hypertension Treatment Study (OHTS) reported that diabetes protected against the conversion of OHT to GON. Furthermore, hyperglycemia is neuroprotective in rodent models of acute retinal ischemia and chronic retinal hypoperfusion. The aim of the current work was to investigate the effect of short-term hyperglycemia on optic nerve damage in a rat model of experimental glaucoma.

Methods: : Adult Sprague-Dawley rats were divided into two groups: the first was made hyperglycemic by intraperitoneal injection of streptozotocin 4 days before induction of GON (n=26) and the second remained normoglycemic (n=28). Experimental GON was induced by lasering the trabecular meshwork using a standard protocol. After two weeks of elevated intraocular pressure, rats were killed by transcardial perfusion.The optic nerves were dissected and processed for transverse and longitudinal analysis. Axonal loss was graded semi-quantitatively, by a well characterised methodology, on transverse sections. The longitudinal sections were immunohistochemically stained for the microglial markers ED1 and Iba1. The histological/immunohistochemical outcomes for each group were compared using unpaired, non-parametric statistics.

Results: : The degree of axonal loss following 2 weeks of experimental glaucoma was significantly lower in the hyperglycemic group of rats compared to the normoglycemic group. Specifically, axonal loss in the hyperglycemic animals was 8.8% versus 19.3% in the normoglycemic rats. This equates a 54% reduction in damage, which was statistically significant. Experimental glaucoma caused a marked proliferation and activation of microglia, as assessed by ED1 and Iba1, within the optic nerve, which correlated well with the degree of axonal damage measured by optic nerve grading. Increases in ED1 and Iba1 were significantly lower in the hyperglycemic rats.

Conclusions: : Underlying hyperglycemia appeared to be protective in this rat model of experimental GON after 2 weeks of OHT. Possible explanations for this effect are the attenuation of malperfusion induced energy failure by increasing the substrate for glycolysis or a shift in metabolism resulting in reduction of ROS-induced apoptosis. Further studies are needed to elucidate the potential of this novel neuroprotective strategy.

Keywords: neuroprotection • metabolism • optic nerve 
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