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. 2014 Jun;184(6):1660–1667. doi: 10.1016/j.ajpath.2014.02.007

Figure 2.

Figure 2

Progressive age-dependent RPE abnormalities in heterozygous VMD2-Cre mice (Cre+/WT). A: Quantitative analysis shows that RPE cell size of Cre-expressing (Cre+/WT; gray bars) cells compared with Cre-negative (black bars) cells is unchanged in 1-month-old heterozygous VMD2-Cre mice (het), whereas Cre-expressing (Cre+/WT) RPE cells in 4- and 7-month-old heterozygous VMD2-Cre mice show a significant reduction in cell size. B: Scoring cytoplasmic active β-catenin labeling in Cre-expressing (Cre+/WT) and Cre-negative RPE cells reveals a significant attenuation of cytoplasmic active β-catenin with progressive age in heterozygous VMD2-Cre mice. C: One-month-old heterozygous VMD2-Cre mice show Cre-expressing (Cre+/WT) RPE cells with normal cell morphology and normal cytoplasmic active β-catenin staining (long arrow), compared with adjacent Cre-negative RPE cells (short arrow). D: A representative image of a choroidal flat mount from a 7-month-old heterozygous VMD2-Cre mouse (Cre+/WT). Although Cre-negative cells show normal cell size and honeycomb morphology with uniform cytoplasmic active β-catenin staining, Cre-expressing (Cre+/WT) cells show loss of cytoplasmic active β-catenin staining and atypically formed small RPE cells (white arrow). Notably, some Cre-expressing (Cre+/WT) cells appear normal (black arrow). A subset of Cre-expressing (Cre+/WT) cells show a displacement of cell nuclei toward the periphery, opposed to the normal central or paracentral localization of RPE cell nuclei (yellow short arrows). Although normal RPE cells show one or two cell nuclei, few Cre-expressing (Cre+/WT) cells show three nuclei (short white arrow). E and F: Phalloidin labeling of the flat mounts shown in C and D. Although 1-month-old heterozygous VMD2-Cre mice show normal phalloidin labeling of Cre-expressing (Cre+/WT) cells (E, long arrow) as seen in adjacent Cre-negative cells (E, short arrow), 7-month-old heterozygous VMD2-Cre mice show loss of phalloidin labeling in Cre-expressing (Cre+/WT) cells, while adjacent Cre-negative RPE cells show normal phalloidin labeling (arrows as in D). G and H: Age-matched 1- or 7-month-old wild-type control mice do not show these RPE abnormalities and instead reveal a uniform labeling pattern for phalloidin (lower part of images) and cytoplasmic active β-catenin (upper part of images), which is maintained with increasing age of the mice. Data are expressed as means ± SD. n = 3 mice per group (A and B). ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. Scale bars: 100 μm.