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Haihan Jiao, Laura Elizabeth Downie, Sara Oberrauch, Mengliang Wu, Holly Rose Chinnery, Laura Jacobson; Novel alterations to the corneal neuroimmune phenotype in mice with central nervous system tauopathy.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1352.
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© ARVO (1962-2015); The Authors (2016-present)
Disruptions to the microtubule protein tau in the central nervous system are a core, characteristic pathology of Alzheimer’s disease (AD). Although AD is accompanied by various ocular changes, the effects of tau pathology on the integrity of the cornea are still unknown. The corneal epithelium has a rich supply of sensory nerves and a well characterised population of resident dendritic cells (DCs). We investigated the morphological changes in the corneal sensory nerves and resident DCs using a transgenic mouse model of tau pathology (rTg4510).
We used 8- and 11-month old rTg4510 transgenic mice, which overexpress hyperphophorylated tau, and wild-type (WT) littermates. Anterior segment anatomy was examined using spectral domain optical coherence tomography (SD-OCT). Corneas were processed for wholemount immunofluorescence staining using anti-β-tubulin III and anti-CD45 antibodies. Image J was used to quantify the density of sensory nerves in the subbasal nerve plexus and superficial epithelium. Epithelial DC density and dendritic tree area were also compared between the two groups.
In 8-month old mice, the density of corneal nerves in the sub-basal nerve plexus (SBNP) was significantly lower in the peripheral cornea of rTg4510 mice compared to WT mice (P<0.05, n=6 per group), but the density of vertical axons and superficial nerve terminals (SNT) was similar in both genotypes. In 11-month old mice, the density of SBNP and SNT was lower in rTg4510 mice in both the central and peripheral cornea (P<0.05). The morphology of nerve axons in the SBNP was altered in rTg4510 mice, with a higher percentage of beaded nerves visible compared to WT mice (P<0.05, n=7 per group). The density of DCs was lower in the corneal epithelium of rTG4510 mice compared to WT mice in 8 month and 11 month old mice (P<0.05). The dendritic tree area of epithelial DCs was also smaller in rTg4510 mice compared to WT mice in both age groups (P<0.05). Corneal thickness and architecture was similar across all age groups and genotypes.
The corneal nerves and resident immune cells are altered in the rTg4510 mouse model , suggesting involvement of the cornea in AD-related tauopathy. This identifies the cornea as a useful window to visualise the peripheral nervous system pathology that occurs in age-related neurodegenerative disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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