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Jeremiah K.H. Lim, Zheng He, Algis J Vingrys, Holly Rose Chinnery, Qiao-Xin Li, Bang V Bui, Christine Tram Oanh Nguyen; Age-related changes in retinal structure and function in a mouse model of Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):613. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Recent findings suggest ocular changes parallel brain changes in Alzheimer’s disease (AD). We investigate if AD mice show greater structural and function deficits in the retina with age.
Familial Alzheimer’s Disease mouse model B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax (5xFAD) was studied at 6 (6mo,N=7) and 17 months (17mo,N=8) of age, along with matching wild type (WT) littermates. Retinal function (photoreceptors:P3; bipolar:P2; amacrine:OPs; ganglion:pSTR) was characterised under anaesthesia (80:10 mg/kg ketamine:xylazine) using scotopic electroretinography (ERG). Structure (nerve fibre:RNFL; ganglion cell complex:GCC; total retinal thickness:TRT) was assessed using Optical Coherence Tomography (OCT). ERG and OCT are expressed relative to young (6mo) WT controls (%±SEM). One-way ANOVA compared parameters between groups. Paraffin sections of eye and brain tissues were stained with monoclonal amyloid-β (Aβ) antibodies (1E8, 1:200) and quantified using ELISA to assess Aβ content (Brain:N=6; Retina: pooled).
Deficits were observed at 6mo 5xFAD mice in the pSTR (83±14% of WT, P<0.05) but not in other ERG components when compared with WT (P3:100±6, P2:107±9, OPs:100±7%). At 17 mo, WT mice showed age-related reductions in all ERG components (P3:87±3, P2:84±3, OPs:87±7, pSTR:54±9%, P<0.05). Transgenic 5xFAD mice of 17 mo showed both age and strain related declines in function, particularly in the pSTR (P3:56±11, P2:58±9, OP:52±13, pSTR:28±11, P<0.05). At 6mo, OCT in 5xFAD mice showed significant RNFL thinning (72±4, P<0.05) but no change in GCC or TRT (95±1; 100±1% respectively). At 17mo, WT mice showed no ageing changes (RNFL: 91±5, GCC:96±1, TRT:101±1%). At 17mo, 5xFAD showed a strain effect in RNFL (70±3% P<0.05) but not in GCC and TRT (90±1, TRT 100±1% respectively). Between 6 and 17 mo, there was no further change in OCT. Histology showed Aβ deposition in the hippocampus and cortex in 5xFAD at both ages. ELISA showed Aβ content in brain and retina tissue in 17 mo 5xFAD (14.5±2.2, 14.5pg/mg respectively) but not detectable in WT.
Both young and older 5xFAD mice have worse inner retinal function than WT mice. RNFL thinning was present in 6mo animals but did not appear to progress at 17mo. Despite the lack of overt structural decline beyond 6 months of age, retinal function continued to decline in 5xFAD 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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