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Peter Charbel Issa, Alun R. Barnard, Mandeep S. Singh, Emma Carter, Roxana A. Radu, Ulrich Schraermeyer, Robert E. MacLaren; Fundus Autofluorescence in the Abca4-/- Mouse, an Animal model for Stargardt disease - Correlation with Retinal Function, Histology and Accumulation of A2E. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4988.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the feasibility of quantitative and qualitative fundus autofluorescence (AF) assessment for monitoring lipofuscin accumulation in the Abca4-/- mouse, and to correlate findings with retinal function, histology and measurements of A2E.
Confocal scanning laser ophthalmoscopy (cSLO) was used for in vivo fundus AF excited at 488 nm in pigmented Abca4-/- mice and wild type controls. For quantitative AF analysis, the mean grey level on fundus AF images acquired with standardized detector sensitivity was measured within a ring shaped midperipheral area. Additional analysis included electroretinography (ERG), post-mortem histological assessment of the outer nuclear layer thickness, and measurements of A2E using HPLC.
Fundus AF intensity was similar in four weeks old animals. With age, a steady increase of AF occurred, which was more pronounced in Abca4-/- mice compared to wild type controls. Fundus AF was significantly higher (p<0.01) in Abca4-/- mice at 9 weeks and older. The grey level ratio between Abca4-/- and age-matched wild type mice, which accounts for confounding factors such as pupil size or other age-related changes, was 1.2 at 4 weeks, 2.0 at 3 months, and 2.25 at 6 months. A fleck pattern of high fundus AF was clearly visible in 6 month old Abca4-/- mice, but not in wild type controls. In Abca4-/- mice 12 months and older, there were spots of decreased AF suggesting atrophic changes of the retinal pigment epithelium.ERG a-wave and b-wave amplitudes and the outer nuclear layer thickness were not significantly different between Abca4-/- mice and wild type controls up to an age of 9 months. Total A2E measurements increased similar to fundus AF measures. However, the ratio was 4-5 times higher than on fundus AF measures, possibly due to other fluorophores contributing to the overall difference.
cSLO imaging in mice allows detecting significant differences in fundus AF intensity and pattern between Abca4-/- mice and wild type controls in age groups that show no significant difference in photoreceptor function (ERG) and number (outer nuclear layer thickness). Thus, fundus AF imaging is a useful technique to assess potential treatments aiming at reducing lipofuscin accumulation in the retinal pigment epithelium.
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