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Federica Staurenghi, Cristina Martinez-Fernandez dela Camara, Alun R Barnard, Robert E MacLaren; Fundus autofluorescence abnormalities and microglia/macrophage activation in the Rpgr-deficient mouse.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):433.
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© ARVO (1962-2015); The Authors (2016-present)
Fundus autofluorescence (AF) imaging is a technique widely used in the clinic to diagnose and monitor retinal diseases. Abnormally increased or decreased 488 nm AF, or specific alterations of the AF pattern have been associated to different retinal degenerations. The aim of this study was to investigate fundus AF abnormalities in the Rpgr-deficient mouse and its correlation with microglia activation and photoreceptor cell degeneration.
Blue (488 nm) fundus AF imaging was performed using a scanning laser ophthalmoscope (SLO) in Rpgr knock out (KO) mice and wild type (WT) controls from 1 to 9 months of age (n=5 per group). Optical coherence tomography (OCT) was used to detect structural changes in the retina and measure the thickness of the outer nuclear layer (ONL) over time. Distribution of microglia/macrophages in retina was evaluated by immunostaining of specific markers, such as Iba1, in retinal cryosections and flatmount retinas.
The Rpgr KO mouse exhibited hyper-AF punctae distributed throughout the retina and increasing in number with age. OCT analysis showed a progressive reduction of the ONL thickness in the Rpgr KO mouse, but no other structural alterations coincident with hyper-AF punctae. Immunohistochemistry analysis revealed that, in Rpgr KO retinas, Iba1-positive cells were abundant in the outer layers of the retina, where they had an amoeboid shape with fewer branches compared to cells in the inner retina. Iba1-positive cells were most evident and abundant in the outer retina of 3 months old Rpgr KO eyes and appeared to reduce in number by 6 months of age.
The Rpgr KO mouse shows hyper-AF punctae on SLO imaging that increase in number as the animal ages. The KO line also shows numerous Iba1-positive cells in the outer layers of the retinas, which appear to peak in number around 3 months of age and then decline. As the time courses appear to be different, the accumulation of hyper-AF punctae cannot be exclusively attributable to the increased presence of Iba1-positive cells in the outer layer of the retina. This suggests that there is an additional cellular source responsible for the fundus AF abnormalities observed in this mouse model and it remains to be determined whether these cells are helpful of harmful in the progression of photoreceptor cell death in the Rpgr KO mouse.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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