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Christopher Ardeljan, Chi-Chao Chan, Mones S Abu-Asab; State of Retinal and Choroidal Capillaries in Murine AMD Mouse Models: A Comparative Study. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2327.
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© ARVO (1962-2015); The Authors (2016-present)
AMD mouse models such as Ccl2-/- and Ccl2-/-/Cx3cr1-/- have been shown to contain abnormal chromatin and mitochondria in their RPE. We have published on nuclear DNA leakage to the cytoplasm and damaged mitochondria in three AMD mouse models (Ogilvy et al. 2014). Since little is known about the state of retinal and choroidal vascular capillaries in these mice, we sought to determine the scope of ultrastructural aberrations.
Eyes of 24 mice, aged 1.5 to 6 months old, from 4 strains (6/strain), C57BL/6J, C57BL/6N, Ccl2 -/-on C57BL/6N background, and Ccl2 -/-/Cx3cr1 -/- on C57BL/6N background, were enucleated and prepared for transmission electron microscopy.
In the wild type C57BL/6J, choriocapillaries were normal, and endothelial cells had normal cytoplasm. In the wild type C57BL/6N, choriocapillaries had degenerate endothelial cytoplasm, split basement membrane, and fenestration was absent. Bruch’s membrane disintegrated. Retinal vascular mural cells in the OPL and some endothelial cells were degenerate; basement membrane was degenerate, and lumen occluded. In the single knockout Ccl2-/- the choriocapillary wall was very thin with scant cytoplasm and pores absent; endothelial cytoplasm was scant, degenerate, or absent; nuclei were pyknotic, and capillary lumen was occluded. Capillaries in the OPL had degenerate basement membrane and lacked mural cells or mural cells were necrotic, and capillary lumen occluded. In the double knockout Ccl2 -/-/Cx3cr1 -/-, the choriocapillaries as well as capillaries in the inner plexiform layer (IPL), outer plexiform layer (OPL), ganglion cell layer (GCL) and nerve fiber layer (NFL) contained inclusions, and their basement membrane split into pockets. Choriocapillaries lacked pores at the interface with Bruch’s membrane. Endothelial cells in the IPL had degenerative cytoplasm and degeneration of mural cell processes; and nuclei of endothelial cells enlarged filling the capillary’s lumen. Mitochondria of examined mural cells and adjacent fibrocytes are swollen and without inner membranes.
Our ultrastructural survey shows that the aberrations in these AMD mouse models extend beyond degenerate mitochondria and enDNA of retina to both retinal and choroidal vasculature of the eye. The state of the capillaries in the mutant mice suggests that the capillaries also contribute to the pathological phenotype.
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