Loss Of Nrf-2 And Pgc1-Alpha Genes Changes Macromorphology Of The Eye And Evokes Microstructural And Pigmentation Pattern Changes Of The Retinal Pigmented Epithelium

PurposeNrf2 (NF-E2-related factor 2) and PGC1- α (peroxisome proliferator-activated receptor-gamma coactivator 1-alpha) regulate oxidative stress response in cells. Nrf-2 and PGC1-alpha double-knock-out (dKO) mice were used to monitor macro and morphological changes of eye, retina and retinal pigmented epithelium (RPE), respectively.MethodsThe mMRI and mCT imaging were carried out for mice aged at 6 weeks (mCT), 12 weeks and 12 months (mMRI). The retinal and RPE microanatomy and pigmentation were studied from HE-stained thin wax and toluidine blue-stained epoxy sections. Finally, cellular proliferation and pigmentation patterns were studied in the primary cell cultures.ResultsThe dKO samples showed smaller body parameters and weight. mMRI, mCT assays indicated size differences and dysmorphic body features in the dKO mice. Moreover, dKOs exhibited reduced retinal full tickness joined with retained RPE morphology. The melanosomes of dKO RPEs were heterogeneous in shape morphology, but comparable in size to aged matched wild type melanosomes, respectively. However, there was a striking trend of increase in the density of melanosomes in RPE of dKOs that was convinced by the primary RPE cultures.ConclusionsNrf-2/PGC-1α knockout mice provide a novel model to study degenerative changes in retina and RPE.