July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Subretinal Aβ injections induce a localised, early CNV phenotype in C57BL/6 mice
Author Affiliations & Notes
  • Savannah Lynn
    Clinical & Experimental Sciences, The University of Southampton, Southampton, United Kingdom
  • Jennifer Scott
    Clinical & Experimental Sciences, The University of Southampton, Southampton, United Kingdom
  • Helena helenalee100@yahoo.co.uk Lee
    Clinical & Experimental Sciences, The University of Southampton, Southampton, United Kingdom
  • Roshni Desai
    Clinical & Experimental Sciences, The University of Southampton, Southampton, United Kingdom
  • Tracey Newman
    Clinical & Experimental Sciences, The University of Southampton, Southampton, United Kingdom
  • Angela Cree
    Clinical & Experimental Sciences, The University of Southampton, Southampton, United Kingdom
  • Andrew Lotery
    Clinical & Experimental Sciences, The University of Southampton, Southampton, United Kingdom
  • J. Arjuna Ratnayaka
    Clinical & Experimental Sciences, The University of Southampton, Southampton, United Kingdom
  • Footnotes
    Commercial Relationships   Savannah Lynn, None; Jennifer Scott, None; Helena Lee, None; Roshni Desai, None; Tracey Newman, None; Angela Cree, None; Andrew Lotery, None; J. Arjuna Ratnayaka, None
  • Footnotes
    Support  Gift of Sight Grant
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5827. doi:
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      Savannah Lynn, Jennifer Scott, Helena helenalee100@yahoo.co.uk Lee, Roshni Desai, Tracey Newman, Angela Cree, Andrew Lotery, J. Arjuna Ratnayaka; Subretinal Aβ injections induce a localised, early CNV phenotype in C57BL/6 mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5827.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Amyloid β (Aβ) is associated with clinical hallmarks of Age-related macular degeneration (AMD), yet its potential role in AMD pathogenesis remains unknown. The purpose of this study was to test Aβ induced morphological/functional changes to the outer retina in situ by conducting non-invasive retinal imaging techniques in a mouse model.

Methods : Female C57BL/6 mice aged 117±4 days were subject to subretinal injection with 1.5μl 625nM human oligomeric Aβ1-42(n=7), sham(n=6) or 625nM BSA(n=5). At 8 and 15 days post injection full-field electroretinography (ffERG) and optical coherence tomography (OCT) were performed to assess treatment effects compared to baseline. Scotopic ffERGs were conducted by stimulation with 1.5mm diameter, 6.8 cd-s/m2 white LED light for 1ms in 2 sweeps with a 120s interval, from which average A-wave and B-wave amplitudes, and T(A) and T(B) implicit times were calculated. OCT images were acquired as 1.4mm volumetric scans (100 B-scans comprising 1000 A-scans). Scans were segmented at 24 locations using the InVivoVue 2.4 Diver software for Inner segments (IS), Outer segments (OS), Photoreceptor end tips (ETPRS) and the RPE, to assess treatment effects on layer thickness. One-way ANOVA with Tukey’s post hoc test assessed statistical comparisons with individual mice as the statistical unit. Data is presented as mean ± SEM.

Results : Localised subretinal hyperreflective exudation (SHE) and subretinal hyper-reflective material (SHRM) were evident in OCT scans after Aβ1-42 and BSA treatment at 8 and 15 days, with SHE/SHRM reduction associated with subretinal cystic spaces on day 15. No significant difference was seen in global thickness of the IS(p=0.46,p=0.80), OS(p=0.97,p=0.81), ETPRS(p=0.95,p=1.0) or RPE(p=0.95,p=0.28) compared to sham at 8 and 15 days respectively. Similarly, ffERGs saw no significant difference in the A-wave(p=0.94,p=1.00), B-wave(p=0.87,0.89), T(A) (p=0.43,p=0.19) and T(B) (p=0.94,p=0.82) between Aβ and sham at 8 and 15 days.

Conclusions : Aβ exposure induced pathology consistent with an early-CNV phenotype. However, this did not translate to a global reduction in IS, OS, ETPRS or RPE thickness, or retinal function, likely due to the localised nature of pathology observed. Nonetheless, our findings suggest a pro-angiogenic role for Aβ, where cumulative damage over time may cause statistically significant thickness/functional deficits.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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