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Nimesh Bhikhu Patel, Louvenia Carter-Dawson, Ronald S Harwerth; Extracellular Matrix Tissue Content of the Neuroretinal Rim differs in Healthy and Glaucomatous Eyes. Invest. Ophthalmol. Vis. Sci. 2019;60(9):662. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The glaucomatous optic nerve head has characteristic cupping, with thinning of the retinal nerve fiber (RNFL) layer and optic nerve head neuroretinal rim (NRR) tissue. In prior longitudinal studies using optical coherence tomography (OCT), the NRR was shown to thin prior to the circumpapillary RNFL. While retinal ganglion cell (RGC) axons are a major constituent of both NRR and RNFL, its constituents also include glia, vasculature and extracellular matrix. The purpose of this study was to investigate extracellular matrix of the NRR between experimental glaucoma and control eyes in the non-human primate.
Unilateral argon laser application to the trabecular meshwork was used to elevate the intraocular pressure in three monkeys that were followed longitudinally with OCT. Minimum rim width (MRW) was used to quantify the NRR. Animals were euthanized at early and mild stages of neuropathy, as determined by the magnitude of circumpapillary RNFL thickness loss. The optic nerve head was dissected, and the constitution of the extracellular matrix was determined using immunohistochemistry and confocal microscopy. Cell bodies were identified using 4′,6-diamidino-2-phenylindole, glial cells were labeled using glial fibrillary acidic protein, components of the extracellular matrix with antibodies for hyluronan, tenacin C, aggrecan, fibrillin and elastin.
For the three animals, there was a global reduction of OCT quantified MRW of 130 (42%), 181 (63%), and 185µm (46%), and circumpapillary RNFL thickness of 42 (39%), 23 (26%), and 10 (8.8%) µm respectively. Compared to control eyes, the NRR of experimental glaucoma eyes has a significant increase in glial fibrillary acidic protein. While there was a mild increase in tenacin C in all three experimental eyes, there was significant reduction in hyluronan, fibrillin and elastin. The two more advanced eyes also had a reduction in aggrecan.
While RGC axons are the major constituent of both the RNFL and NRR, there are differences in the proportional loss of these measures in glaucoma. It is likely that thinning of these structures with disease not only reflects losses of RGC axons, but also changes in the non-axonal tissue including glia and the extracellular matrix.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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