CRB1rd8 mutation influences the age-related macular degeneration phenotype of NRF2 knockout mice and favors choroidal neovascularization.

We examined the influence of retinal degeneration 8 (rd8) mutation of crumbs homolog 1 (CRB1) gene on age-related macular degeneration (AMD) phenotype in nuclear factor E2-related factor 2 knock out (NRF2-/-) mouse model. CRB1rd8 mutation genotype was determined by polymerase chain reaction from tail clips in 73 NRF2-/- mice originating from C57BL/6J background on mixed C57BL/6J and C57BL/6N ancestry. The clinical grade of AMD-like fundus alterations was determined by funduscopy, optical coherence tomography (OCT) and fluorescein angiography (FLA) at the age of 9 or 12 months. Twelve NRF2-/- mice were wildtype CRB1+/+, 61 NRF2-/- were homozygous CRB1rd8/rd8. NRF2-/-CRB1rd8/rd8 mice had a significantly higher probability to show an advanced grade (grade 4 and 5) of AMD-like fundus alterations known to appear in NRF2-/- mice. Choroidal neovascularization (CNV) was only detected in NRF2-/-CRB1rd8/rd8 homozygous mice. Homozygous CRB1rd8/rd8 mutation is common in commercial vendor mice strains of C57BL/6J origin if partly on C57BL/6N ancestry. The mutation has an influence on the extent of AMD-like retinal alterations in NRF2-/- mice and favors CNV formation.