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Sem Genini, Karina E. Guziewicz, William A. Beltran, Gustavo D. Aguirre; Common Apoptosis-Related miRNA Expression During Chronic Photoreceptor Cell Death in Canine Models. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1622.
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To quantify the expression of selected apoptomirs, apoptosis-related miRNAs, in dogs affected with XLPRA2, rcd1, and erd. These non-allelic retinal diseases are caused by mutations in RPGRORF15, PDE6B, and STK38L, respectively.
qRT-PCR comparisons of 11 miRNAs (miR-9, -19a, -20, -21, -29b, -122, -129, -146a, -155, -183, -221) between mutant and normal retinas (3/group/age) were performed using TaqMan assays. Ct values were normalized with those of U43 small nuclear RNA, the ratio of mutant vs. control calculated with the ddCt method, and differentially expressed (DE) miRNAs identified with an unpaired t-test (p<0.05 and fold change >2).
Minimal differences in miRNA expression were observed at early ages in XLPRA2 and rcd1. At 7 wks, miR-155 was elevated in XLPRA2, rcd1, and erd, while miR-21 was up-regulated in rcd1 and erd. At this age, additional up-regulated miRNAs were disease-specific: miR-9, -146a, -221 in rcd1; -122 in XLPRA2; and -19a, -29b in erd. Notable results for these three early-onset diseases at 16 wks included down-regulation of the pro-apoptotic miR-122 and -129, as well as up-regulation of almost all anti-apoptotic miRNAs, excluding miR-183 whose expression did not vary.
Our results indicate minimal expression differences of apoptomirs at disease onset (3 wks). However, during the peak (5 or 7 wks) of photoreceptor cell death there was only one apoptomir that was DE in common. This suggests that the early (5-7 wks) miRNA expression patterns are likely to be disease-specific. Furthermore, during the chronic cell degeneration phase (16 wks) there was a common signature of miRNA regulation in the three different diseases, especially between XLPRA2- and rcd1-mutants, and to a lesser extent for erd. This follows the pattern of disease in XLPRA2 and rcd1 that is characterized by synchronized photoreceptor cell death. In contrast, erd has a unique pattern of photoreceptor cell death or proliferation that occurs in parallel in this time period.
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