Abnormal retinal pigment epithelium melanogenesis as a major determinant for radiation-induced congenital eye defects

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@article{1e976030375741df93ef745011907cfa,
title = "Abnormal retinal pigment epithelium melanogenesis as a major determinant for radiation-induced congenital eye defects",
abstract = "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.",
keywords = "Congenital defects, Radiation, Retinal pigment epithelium, Pigmentation, Eye abnormalities, Microthalmos, Anophthalmos, Exencephaly",
author = "Kai Craenen and Mieke Verslegers and Livine Craeghs and Roel Quintens and Amelie Coolkens and Sarah Baatout and Lieve Moons and Rafi Benotmane",
note = "Score=10",
year = "2019",
month = "11",
day = "6",
language = "English",
volume = "91",
pages = "59--73",
journal = "Reproductive toxicology",
issn = "0890-6238",
publisher = "Elsevier",

}

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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 - 2019/11/6

Y1 - 2019/11/6

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

M3 - Article

VL - 91

SP - 59

EP - 73

JO - Reproductive toxicology

JF - Reproductive toxicology

SN - 0890-6238

ER -

ID: 6842621