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

Kai Craenen; Mieke Verslegers; Livine Craeghs; Roel Quintens; Ann Janssen; Amelie Coolkens; Sarah Baatout; Lieve Moons; Mohammed Abderrafi Benotmane

doi:10.1016/j.reprotox.2019.10.002

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

Reprod Toxicol. 2020 Jan:91:59-73. doi: 10.1016/j.reprotox.2019.10.002. Epub 2019 Nov 6.

Authors

Kai Craenen¹, Mieke Verslegers², Livine Craeghs¹, Roel Quintens², Ann Janssen², Amelie Coolkens², Sarah Baatout², Lieve Moons³, Mohammed Abderrafi Benotmane⁴

Affiliations

¹ Radiobiology Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre SCK-CEN, Boeretang 200, Mol 2400, Belgium; Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology section, Department of Biology, Faculty of Science, KU Leuven, Naamsestraat 61 bus 2464, Leuven 3000, Belgium.
² Radiobiology Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre SCK-CEN, Boeretang 200, Mol 2400, Belgium.
³ Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology section, Department of Biology, Faculty of Science, KU Leuven, Naamsestraat 61 bus 2464, Leuven 3000, Belgium.
⁴ Radiobiology Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre SCK-CEN, Boeretang 200, Mol 2400, Belgium. Electronic address: rafi.benotmane@SCKCEN.be.

PMID: 31705956
DOI: 10.1016/j.reprotox.2019.10.002

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 unexplored, we irradiated pregnant C57BL/6J mice (1.0 Gy, X-rays) at embryonic day (E)7.5, followed by histological 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: Anophthalmos; Congenital defects; Exencephaly; Eye abnormalities; Microphthalmos; Pigmentation; Radiation; Retinal pigment epithelium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Embryonic Development / radiation effects
Female
Gene Expression Regulation, Developmental / radiation effects
Melanins / metabolism*
Mice, Inbred C57BL
Organ Size / radiation effects
Radiation Injuries, Experimental / genetics
Radiation Injuries, Experimental / metabolism*
Retinal Pigment Epithelium / abnormalities
Retinal Pigment Epithelium / metabolism
Retinal Pigment Epithelium / radiation effects*
X-Rays / adverse effects*

Substances

Melanins