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Kristin Hösel, Jan Tode, Elisabeth Richert, Claus von der Burchard, Alexa Klettner, Johann Roider; Drusen-like Retinal Spots in NRF2-/- AMD Mouse Model correlate either to epi-RPE or sub BrM localization. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2992.
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© ARVO (1962-2015); The Authors (2016-present)
Current understanding of age related macular degeneration (AMD) pathogenesis is mainly based on cell and animal models. Drusen are a hallmark for AMD, however the nature and determination of drusen-like retinal spots (DRS) clinically depends on the observer’s interpretation. We analyzed DRS in the nuclear factor E2-related factor 2 knock out (NRF2-/-) AMD mouse model.
Six 10 months old NRF2-/- mice were examined clinically by funduscopy, optical coherence tomography (OCT) and fluorescein angiography (FLA) in deep anesthesia. Mice were euthanized and eyes were collected for histological preparation (HE staining). Clinical fundus findings were correlated to histological findings. All mice were genotyped for crumbs homologue gene (CRB)-1 retinal degeneration (rd)8 mutation and NRF2 genotype.
All mice were homozygous NRF2-/- and homozygous for rd8 mutation. 5/6 mice showed multiple yellow/white retinal spots. By means of OCT these findings could be attributed either to an epi RPE (retinal pigment epithelium) or to a sub-Bruch’s membrane (BrM) localization. Epi-RPE spots could be correlated histologically to drusen-like deposits between RPE and photoreceptor outer segments. Sub-BrM spots could be correlated histologically to loss of pigment in the otherwise pigmented choroid of the mouse. Larger diameter choroidal vessels were surrounded by immune cells in these areas, or granuloma-like cell conglomerates formed depigmented spots within the choroid. There were significantly more sub-BrM (mean 40 +/- 44 SD) than epi-RPE (mean 2 +/- 3 SD) spots.
Finding an appropriate murine model to study AMD pathomechanisms or for translational research is a challenge for many reasons. An AMD-like phenotype with DRS has been described before. These fundus alterations need to be differentiated concerning their content and localization. We can show that retinal spots clinically resembling drusen may be alterations at the choroid level rather than real drusen. Our findings may help others to interpret AMD-like fundus alterations.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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