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J Cameron Millar, Hannah C. Webber, Tien Phan, Sandra Neubauer, Abbot F Clark; PRIMARY OPEN ANGLE GLAUCOMA AND ALZHEIMER’S DISEASE: IS THERE AN ASSOCIATION IN 5XFAD MICE?. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2543.
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© 2017 Association for Research in Vision and Ophthalmology.
Primary open-angle glaucoma (POAG) and Alzheimer’s Disease (AD) are neurodegenerative disorders. POAG is a major cause of vision loss, characterized by apoptosis of retinal ganglion cell (RGC) axons, and optic nerve head neuropathy. Intraocular pressure (IOP) is often increased. AD is a major cause of dementia and impacts cognition, including: memory, functionality, personality, and behavior. Increased prevalence of POAG amongst AD patients has been reported. In AD, Amyloid-beta (Aβ) plaques are deposited in the CNS. In mouse models of POAG, Aβ has been found in RGCs and retinas of affected eyes. 5XFAD mice express several familial AD mutations, and develop Aβ plaques, cognitive deficits, and neurodegeneration. We assessed 5XFAD mice at various ages for POAG.
In live 5XFAD mice and WT controls (C57) (n=10 mice, each group), we conducted: (1) weekly IOP measurements; (2) pattern electroretinography (PERG), and (3) outflow facility (C) measurements. Animals were sacrificed at various ages and whole eyes harvested/fixed. 5µm sagittal sections were prepared. Some sections were stained (H&E) to determine RGC counts/section and retinal layer thicknesses. Others were immunostained (anti-Aβ Ab) to determine if Aβ was expressed in the retina or chamber angle.
5XFAD mice exhibited a ~6-week periodic cyclical IOP disturbance (amplitudes ~4-6mmHg), commencing at age 14 weeks. Immunostaining revealed Aβ in photoreceptors, RPE, and chamber angle, but not RGCs. PERG amplitude and C both declined (but not significantly) over 15-24 weeks (PERG, 31.27±10.85 vs. 23.04±4.71µV (P=0.26); C, 0.017±0.002 vs. 0.014±0.002µL/min/mmHg (P=0.13)) (mean±SEM). At 16 weeks, RGC counts (405.92±35.53) were greater than those from eyes 24 weeks (382.64±17.19), but the difference did not reach significance (P=0.17). Retinal layer thicknesses were greater in 24 week sections compared with 16 weeks, but the increases were not significant. In control mice no change in IOP or C was seen and Aβ was not detected.
5XFAD mice accumulate Aβ in their photoreceptors, RPE, and chamber angle. They exhibit disturbed IOP patterns from 14 weeks. They may also progressively lose RGCs and exhibit increased retinal layer thicknesses, and develop reduced PERG amplitude. Studies are on-going to further characterize these findings in older mice.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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