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Melissa Cooper, David J Calkins; Energy Transfer between Normal and Glaucomatous Optic Projections in Mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2011. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The most prevalent optic neuropathy is glaucoma, which is projected to afflict 80 million people worldwide by 2020. Glaucoma challenges retinal ganglion cell (RGC) RGC axons through sensitivity to intraocular pressure (IOP). This sensitivity causes functional and structural deficits within the optic projection even as the RGC body and axon segment in the retina persist. We have shown that axons expand with diminished mitochondrial density prior to frank degeneration, contributing to metabolic stress. We propose that these changes tax normal energy utilization and increases neuronal reliance on astrocyte-derived energy sources.
IOP was unilaterally elevated in mice via microbead occlusion of aqueous flow. IOP was monitored for up to 4 weeks using Tono-Pen XL rebound tonometry. Glycogen content was determined using Abcam glycogen assay ab65620. 1 week after unilateral IOP elevation, a subset of animals received an intravitreal (IVT) injection of 18F-FDG, a radioactive glucose analogue, in the contralateral naïve eye. After allowing 1 hour for uptake, the % injected dose transferred to the stressed optic nerve from the naïve eye was determined using positron emission tomography (PET) with a CT scan for reference.
Microbead occlusion significantly elevated IOP in all conditions (18.31±0.5188 vs 14.27±0.4108 mmHg; p<0.001). 4 days of IOP elevation result in a trend toward diminished glycogen stores in the microbead nerve compared to saline (p=0.058). However, 1 and 2 weeks after unilateral IOP elevation, saline nerves contain less glycogen than contralateral microbead nerves (p=0.014; p=0.083). Further, 1-4 weeks of unilateral IOP elevation cause glycogen stores to diminish in both the microbead and saline nerve compared to naïve levels (p<0.001; p<0.001; p<0.001). PET scans after IVT injection of 18F-FDG in the naïve eye show that glucose moves from the healthy to the stressed optic projection. This occurs to a much greater extent after 1 week of IOP elevation compared to naïve control animals (p<0.001).
After chronic IOP elevation, the contralateral internal control nerve demonstrates deficits in astrocytic energy reserves. Additionally, glucose moves to the stressed tissue from the healthy contralateral nerve. This evidence suggests a novel protective function of astrocytes, wherein they redistribute resources from healthy regions of the brain to areas actively undergoing stress.
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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