TY - JOUR
T1 - Abnormal retinal pigment epithelium melanogenesis as a major determinant for radiation-induced congenital eye defects
AU - Craenen, Kai
AU - Verslegers, Mieke
AU - Craeghs, Livine
AU - Quintens, Roel
AU - Coolkens, Amelie
AU - Baatout, Sarah
AU - Moons, Lieve
AU - Benotmane, Rafi
N1 - Score=10
PY - 2020/1
Y1 - 2020/1
N2 - Recent studies highlighted a link between ionizing radiation exposure during neurulation and birth defects such as microphthalmos and anophthalmos. Because the mechanisms underlying these defects remain largely un-explored, we irradiated pregnant C57BL/6J mice (1.0 Gy, X-rays) at embryonic day (E)7.5, followed by histo-logical and gene/protein expression analyses at defined days. Irradiation impaired embryonic development at E9 and we observed a delayed pigmentation of the retinal pigment epithelium (RPE) at E11. In addition, a reduced RNA expression and protein abundance of critical eye-development genes (e.g. Pax6 and Lhx2) was observed. Furthermore, a decreased expression of Mitf, Tyr and Tyrp1 supported the radiation-induced perturbation in RPE pigmentation. Finally, via immunostainings for proliferation (Ki67) and mitosis (phosphorylated histone 3), a decreased mitotic index was observed in the E18 retina after exposure at E7.5. Overall, we propose a plausible etiological model for radiation-induced eye-size defects, with RPE melanogenesis as a major determining factor.
AB - Recent studies highlighted a link between ionizing radiation exposure during neurulation and birth defects such as microphthalmos and anophthalmos. Because the mechanisms underlying these defects remain largely un-explored, we irradiated pregnant C57BL/6J mice (1.0 Gy, X-rays) at embryonic day (E)7.5, followed by histo-logical and gene/protein expression analyses at defined days. Irradiation impaired embryonic development at E9 and we observed a delayed pigmentation of the retinal pigment epithelium (RPE) at E11. In addition, a reduced RNA expression and protein abundance of critical eye-development genes (e.g. Pax6 and Lhx2) was observed. Furthermore, a decreased expression of Mitf, Tyr and Tyrp1 supported the radiation-induced perturbation in RPE pigmentation. Finally, via immunostainings for proliferation (Ki67) and mitosis (phosphorylated histone 3), a decreased mitotic index was observed in the E18 retina after exposure at E7.5. Overall, we propose a plausible etiological model for radiation-induced eye-size defects, with RPE melanogenesis as a major determining factor.
KW - Congenital defects
KW - Radiation
KW - Retinal pigment epithelium
KW - Pigmentation
KW - Eye abnormalities
KW - Microthalmos
KW - Anophthalmos
KW - Exencephaly
UR - https://ecm.sckcen.be/OTCS/llisapi.dll/open/39180629
U2 - 10.1016/j.reprotox.2019.10.002
DO - 10.1016/j.reprotox.2019.10.002
M3 - Article
SN - 0890-6238
VL - 91
SP - 59
EP - 73
JO - Reproductive toxicology
JF - Reproductive toxicology
ER -