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

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

doi:10.1016/j.reprotox.2019.10.002

Cited by 5 publications

(4 citation statements)

References 79 publications

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“…This phenomenon has also been observed in rodents with a study that dosed pregnant rats with varying levels of radiation on day nine of gestation and performed ocular examinations during postnatal week 5 finding iris and choroidal coloboma, microphthalmia, and anophthalmia in groups dosed with 3.2, 6.3 and 12.6 Gy along with additional ocular malformations in the 12.6Gy group 79 . Further investigation of these observations performed transcriptional analysis on irradiated mice, and linked the structural ocular defects observed to changes in RPE melanogenesis 22 . These studies collectively provide observational and experimental data from both humans and rodents that links radiation exposure to structural ocular defects.…”

Section: F Radiationmentioning

confidence: 99%

Review of evidence for environmental causes of uveal coloboma

Selzer

Blain

Hufnagel

et al. 2022

Survey of Ophthalmology

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Section: F Radiationmentioning

confidence: 99%

Review of evidence for environmental causes of uveal coloboma

Selzer

Blain

Hufnagel

et al. 2022

Survey of Ophthalmology

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“…Even though pre-natal irradiation had no marked impact on the olfactory system in the adult brain, behavioral tests for olfaction were included in the test battery. This decision was based on a previous study that showed transient transcriptional disturbances in the embryonic head following 1.0 Gy irradiation at E7.5 that were related to the development of the olfactory epithelium (Craenen et al, 2020b). This is an important observation, as the olfactory system starts to develop during this neurulation period (Treloar et al, 2010).…”

Section: Radiation-induced Fetal Morphological Defects and Preventiomentioning

confidence: 99%

“…The fourth potential mode-of-action lies in radiation-induced changes in the transcriptome and proteome. We previously demonstrated that X-irradiation (1.0 Gy) at E7.5 in mice reduced the expression of Lhx2, a key transcription factor for eye, brain and olfactory development (Craenen et al, 2020b). Furthermore, mutations in genes associated with Lhx2 are known to cause birth defects such as exencephaly (Barbera et al, 2002).…”

Section: Potential Mechanisms Underlying Fa-mediated Radioprotectionmentioning

confidence: 99%

“…However, depending on the dose or the developmental stage during which exposure occurs, these conventional shielding strategies may not suffice. Animal studies have shown that the neurulation period in the early embryo is especially radiosensitive with regard to the pathogenesis of radiation-induced NTDs and ED (Russell, 1950(Russell, , 1956Di Majo et al, 1981;Heyer et al, 2000;Craenen et al, 2017Craenen et al, , 2020b, but also in terms of cognitive disabilities and altered vision. Indeed, a decreased visual acuity in atomic-bomb survivors, irradiated in the first trimester, and born from mothers with acute radiation syndrome (≤2 km from hypocenter) has been reported (Burrow et al, 1964).…”

Section: Introductionmentioning

confidence: 99%

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Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation

Craenen

Verslegers

Callaerts-Végh

et al. 2021

Front. Behav. Neurosci.

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Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.

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