Purchase this article with an account.
Vickie Wong, Christine Tram Oanh Nguyen, Patricia Jusuf, Jeremiah K.H. Lim, Mourad Tayebi, Bang V Bui; Morphological changes to retinal ganglion cells in a murine model of Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5992.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To define retinal ganglion cell (RGC) morphology and function in relation to retinal structure in a transgenic murine model of Alzheimer’s disease
In 10 months old APP/PS1 (amyloid precursor protein and presenilin 1 mutations; n=8) and age-matched congenic littermates (WT: n=7), in vivo assessment (ketamine:xylazine, 80:10 mg/kg) of RGC function was assayed (dark-adapted electroretinography: scotopic threshold response), along with retinal structure (optical coherence tomography, OCT) and vasculature (OCT angiography). Following in vivo assays, a subset of eyes was enucleated for morphological analysis of RGCs (WT: n=17 RGCs, APP/PS1: n=10 RGCs). Individual RGCs were diolistically labelled with lipophilic dyes (DiI, DiD, DiO) using the Helios Gene Gun System (80 psi helium pulse). RGC dendritic fields imaged using confocal microscopy were skeletonised and quantified with Sholl analysis (5 μm rings; Fiji) to return dendritic branch complexity and area under the curve (AUC). Blood vessel density and the number of junctions within the superficial vessel complex were examined using AngioTool. Retinal layer thicknesses were extracted from the structural OCT for the same retinal regions. All data are shown as mean ± SEM. Unpaired two-tailed t-test was used for statistical analyses.
No significant differences were observed in RGC function (WT: 27.9±2.9 vs APP/PS1: 25.6±4.3 μV; P=0.691) and ganglion cell layer thickness (WT: 24.5±0.4 vs APP/PS1: 24.5±0.3 μm; P=0.167). Similarly, superficial vessel complex density (WT: 13.1±0.7 vs APP/PS1: 11.4±0.8 %; P=0.127) and total number of junctions (WT: 41.9±2.6 vs APP/PS1: 34.3±3.0; P=0.072) were not different between groups. Interestingly, RGCs from APP/PS1 mice had significantly smaller dendritic field diameter (204.9±13.1 μm) than their littermates (260.7±16.0 μm; P=0.022). Sholl analysis revealed that APP/PS1 RGCs have significantly fewer intersections between 10 to 115μm from the cell soma (P<0.05; peak number of intersections 19.1±2.4 vs. WT: 32.1±3.2) and a smaller AUC (3509±357 vs. WT: 6598±512 AU; P<0.001).
In APP/PS1 mice, RGC morphological changes appear to precede detectable difference in function and structural changes measured in vivo. This work lays the foundation for future studies to investigate whether early morphological changes in the retina can predict cortical neurodegeneration in Alzheimer’s disease.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only