Figure 1. Reduced RPE mtDNA gene expression and diminished OXPHOS capacity in RPEΔMT mice.

(A–D) In situ hybridization demonstrates reduced Cox1 mRNA expression in most RPE cells of a 5-week-old albino RPEΔMT mouse (B and D) compared with that of a control (A and C), which refers to littermates with genotype of Tfam^loxp/loxp hereafter, unless otherwise stated. (A and B) original magnification, ×200. (C and D) Original magnification, ×400. (E) Relative mRNA levels of Tfam and 3 mitochondrial-encoded genes were measured by Q-PCR in pigmented RPEΔMT RPE cells. Error bars represent the average deviation from 2 independent experiments. RPE cells from 6 RPEΔMT mice were pooled for each experiment. (F–I) Enzyme histochemical costaining for SDH and COX at 6 weeks shows diminished COX enzymatic activity specifically in a majority of albino RPEΔMT RPE cells (G and I) compared with that of a control (F and H). Cells with normal COX and SDH activity appear brown, whereas COX-adeficient cells appear blue. (F and G), original magnification, ×50. (H and I) Original magnification, ×400. (J and K) Enlarged mitochondria with tubular cristae (K, circled) are evident by electron microscopy in 35-week-old pigmented RPEΔMT RPE. (L) Quantification of maximal area of mitochondria (mito) in 35-week-old RPEΔMT mice (n = 3) and controls (n = 3). Scale bar: 2 μm. ^#P < 0.001.