Frontiers in neurology · 2026
Longitudinal assessment of intraocular pressure in the 5xFAD mouse model of Alzheimer's disease.
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Rubinshtein Raz, Obied Basel, Salti Talal, König Andres I, Zahavi Alon, Goldenberg-Cohen Nitza
Аннотация
OBJECTIVES: Glaucoma and Alzheimer's disease (AD) are major neurodegenerative disorders with increasing evidence of shared pathogenic pathways. Glaucoma involves progressive optic nerve degeneration and irreversible vision loss, often associated with elevated intraocular pressure (IOP) but also occurring independently of it. AD, the leading cause of dementia, results in progressive cognitive and functional decline, with vision disturbances including visual field defects. Epidemiological studies report higher co-prevalence of glaucoma and AD in older adults. This study longitudinally assessed IOP in a transgenic AD mouse model to determine whether AD-related amyloid pathology inherently drives alterations in ocular pressure.
METHODS: Ten young (25 weeks old; 9 males, 1 female) and fifteen aged 5xFAD (57-60 weeks old; 5 males and 10 females) transgenic mice, a well-established amyloidogenic model of AD, were examined. Age-matched control groups included ten young wild type (WT) mice (9 males and 1 female) and fourteen aged WT mice (7 males and 7 females). IOP was measured repeatedly without anesthesia using a rebound tonometer (Icare Tonolab) calibrated for mice. Four IOP measurement sessions were performed at days 1, 36, 55, and 77, with all measurements conducted during midday hours (11:00-14:00) to minimize circadian variability.
RESULTS: IOP remained stable across most groups and time points. Aged 5xFAD mice exhibited transient, statistically significant fluctuations, characterized by an initial decrease at day 36 followed by a return to baseline levels. Age-matched WT mice showed no significant longitudinal changes. When comparing between groups, the only significant difference was observed at day 36, where aged 5xFAD mice demonstrated significantly lower IOP than aged WT controls.
CONCLUSIONS: 5xFAD mice did not exhibit sustained IOP elevation compared with WT controls, with aged animals displaying only transient fluctuations that likely reflect physiological or measurement variability. These results suggest that amyloid-driven pathology in this model is not accompanied by chronic ocular hypertension. Consequently, our findings support the hypothesis that visual dysfunction in AD models may occur independently of elevated intraocular pressure, though the specific overlapping mechanisms between AD and glaucoma warrant cautious interpretation and further investigation.
METHODS: Ten young (25 weeks old; 9 males, 1 female) and fifteen aged 5xFAD (57-60 weeks old; 5 males and 10 females) transgenic mice, a well-established amyloidogenic model of AD, were examined. Age-matched control groups included ten young wild type (WT) mice (9 males and 1 female) and fourteen aged WT mice (7 males and 7 females). IOP was measured repeatedly without anesthesia using a rebound tonometer (Icare Tonolab) calibrated for mice. Four IOP measurement sessions were performed at days 1, 36, 55, and 77, with all measurements conducted during midday hours (11:00-14:00) to minimize circadian variability.
RESULTS: IOP remained stable across most groups and time points. Aged 5xFAD mice exhibited transient, statistically significant fluctuations, characterized by an initial decrease at day 36 followed by a return to baseline levels. Age-matched WT mice showed no significant longitudinal changes. When comparing between groups, the only significant difference was observed at day 36, where aged 5xFAD mice demonstrated significantly lower IOP than aged WT controls.
CONCLUSIONS: 5xFAD mice did not exhibit sustained IOP elevation compared with WT controls, with aged animals displaying only transient fluctuations that likely reflect physiological or measurement variability. These results suggest that amyloid-driven pathology in this model is not accompanied by chronic ocular hypertension. Consequently, our findings support the hypothesis that visual dysfunction in AD models may occur independently of elevated intraocular pressure, though the specific overlapping mechanisms between AD and glaucoma warrant cautious interpretation and further investigation.