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

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  • KUL - Katholieke Universiteit Leuven

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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.

Details

Original languageEnglish
Pages (from-to)59-73
Number of pages15
JournalReproductive toxicology
Volume91
Publication statusPublished - 6 Nov 2019

Keywords

  • Congenital defects, Radiation, Retinal pigment epithelium, Pigmentation, Eye abnormalities, Microthalmos, Anophthalmos, Exencephaly

ID: 6842621