RT Journal Article
SR Electronic
T1 Genetic ablation of the DNA demethylation pathway in retinal progenitor cells impairs photoreceptor development and function, leading to retinal dystrophy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2024.06.19.599771
DO 10.1101/2024.06.19.599771
A1 Dvoriantchikova, Galina
A1 Moulin, Chloe
A1 Fleishaker, Michelle
A1 Almeida, Vania
A1 Pelaez, Daniel
A1 Lam, Byron L.
A1 Ivanov, Dmitry
YR 2024
UL http://biorxiv.org/content/early/2024/06/23/2024.06.19.599771.abstract
AB Rod and cone photoreceptors are critical for vision, and their loss leads to blindness. We explored the role of epigenetic mechanisms in photoreceptor development and function that is still poorly understood. To this end, we created mice in which the DNA demethylation pathway was inactivated in retinal progenitor cells (RPCs). We have shown that DNA demethylation caused by the activity of TET oxidases is necessary during the differentiation of RPCs into photoreceptors. Disruption of the TET-dependent DNA demethylation pathway prevents the proper expression of genes necessary for photoreceptor development and function (e.g., Rho, Nr2e3, Prph2, Pde6a, Pde6b, Pde6g, Cplx4, Grk1, Cnga1, Cngb1, Cplx4). The result of this is underdevelopment or complete absence of outer segments and synaptic termini in photoreceptors of TET-deficient retinas, resulting in loss of rod and cone function, as assayed by electroretinogram. The number of photoreceptors decreases in the TET-deficient retinas over time, leading to retinal dystrophy.Competing Interest StatementThe authors have declared no competing interest.