Radiation-Induced Alterations in Proliferation, Migration, and Adhesion in Lens Epithelial Cells and Implications for Cataract Development

The lens of the eye is one of the most radiosensitive tissues. Although the exact mechanism of radiation-induced cataract development remains unknown, altered proliferation, migration, and adhesion have been proposed as factors. Lens epithelial cells were exposed to X-rays (0.1–2 Gy) and radiation effects were examined after 12 h and 7 day. Proliferation was quantified using an MTT assay, migration was measured using a Boyden chamber and wound-healing assay, and adhesion was assessed on three extracellular matrices. Transcriptional changes were also examined using RT-qPCR for a panel of genes related to these processes. In general, a nonlinear radiation response was observed, with the greatest effects occurring at a dose of 0.25 Gy. At this dose, a reduction in proliferation occurred 12 h post irradiation (82.06 ± 2.66%), followed by an increase at 7 day (116.16 ± 3.64%). Cell migration was increased at 0.25 Gy, with rates 121.66 ± 6.49% and 232.78 ± 22.22% greater than controls at 12 h and 7 day respectively. Cell adhesion was consistently reduced above doses of 0.25 Gy. Transcriptional alterations were identified at these same doses in multiple genes related to proliferation, migration, and adhesion. Overall, this research began to elucidate the functional changes that occur in lens cells following radiation exposure, thereby providing a better mechanistic understanding of radiation-induced cataract development.

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Radiation-induced DNA Damage and Repair in Lens Epithelial Cells of both Ptch1(+/–) and Ercc2(+/–) Mutated Mice

Radiation Research ◽

10.1667/rade-20-00264.1 ◽

2021 ◽

Vol 197 (1) ◽

Author(s):

S. G. R. Barnard ◽

R. McCarron ◽

M. Mancuso ◽

I. De Stefano ◽

S. Pazzaglia ◽

...

Keyword(s):

Dna Damage ◽

Epithelial Cells ◽

Lens Epithelial Cells ◽

Dna Damage And Repair ◽

Radiation Induced

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In vitro exposure of human lens epithelial cells to X-rays at varied dose-rates leads to protein-level changes relevant to cataractogenesis

International Journal of Radiation Biology ◽

10.1080/09553002.2020.1846819 ◽

2020 ◽

pp. 1-13

Author(s):

Vinita Chauhan ◽

Ngoc Q. Vuong ◽

Simran Bahia ◽

Nazila Nazemof ◽

Premkumari Kumarathasan

Keyword(s):

Epithelial Cells ◽

Protein Level ◽

Human Lens ◽

Lens Epithelial Cells ◽

X Rays ◽

Dose Rates ◽

Human Lens Epithelial Cells ◽

In Vitro Exposure

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Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals.

The Journal of Cell Biology ◽

10.1083/jcb.130.1.169 ◽

1995 ◽

Vol 130 (1) ◽

pp. 169-181 ◽

Cited By ~ 210

Author(s):

W C Li ◽

J R Kuszak ◽

K Dunn ◽

R R Wang ◽

W Ma ◽

...

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Cell Apoptosis ◽

Lens Epithelial Cell ◽

Lens Epithelial Cells ◽

Cataract Formation ◽

Cellular Basis ◽

Epithelial Cell Apoptosis ◽

Cataract Development ◽

Cataract Patients

Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed. We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation.

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Protective effects of calbindin‑D28K on the UVB radiation‑induced apoptosis of human lens epithelial cells

International Journal of Molecular Medicine ◽

10.3892/ijmm.2020.4552 ◽

2020 ◽

Author(s):

Kang Liu ◽

Jianfeng Zhao ◽

Liushu Yang ◽

Meng Guan ◽

Ling Yuan ◽

...

Keyword(s):

Epithelial Cells ◽

Human Lens ◽

Lens Epithelial Cells ◽

Protective Effects ◽

Uvb Radiation ◽

Human Lens Epithelial Cells ◽

Radiation Induced ◽

Calbindin D28k ◽

Induced Apoptosis

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Protective effects of appropriate Zn2+ levels against UVB radiation-induced damage in human lens epithelial cells in vitro

JBIC Journal of Biological Inorganic Chemistry ◽

10.1007/s00775-015-1324-9 ◽

2015 ◽

Vol 21 (2) ◽

pp. 213-226 ◽

Cited By ~ 3

Author(s):

Yuxiang Du ◽

Dadong Guo ◽

Qiuxin Wu ◽

Jing Shi ◽

Dongmei Liu ◽

...

Keyword(s):

Epithelial Cells ◽

Human Lens ◽

Lens Epithelial Cells ◽

Protective Effects ◽

Uvb Radiation ◽

Human Lens Epithelial Cells ◽

Radiation Induced

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Over-expression of translationally controlled tumor protein in lens epithelial cells seems to be associated with cataract development

Transgenic Research ◽

10.1007/s11248-009-9283-y ◽

2009 ◽

Vol 18 (6) ◽

pp. 953-960 ◽

Cited By ~ 5

Author(s):

Min-Jeong Kim ◽

Jungmook Lyu ◽

Kyu-Been Sohn ◽

Miyoung Kim ◽

Myeong-Chan Cho ◽

...

Keyword(s):

Epithelial Cells ◽

Lens Epithelial Cells ◽

Over Expression ◽

Translationally Controlled Tumor Protein ◽

Cataract Development

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DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation

Scientific Reports ◽

10.1038/s41598-020-78383-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ion Udroiu ◽

Antonella Sgura ◽

Agnese Chendi ◽

Lorenzo Lasagni ◽

Marco Bertolini ◽

...

Keyword(s):

Dna Damage ◽

Monte Carlo ◽

Epithelial Cells ◽

Lens Epithelial Cells ◽

Eye Lens ◽

Monte Carlo Code ◽

Cataract Formation ◽

X Ray ◽

Radiation Induced ◽

The Relationship

AbstractThe current framework of radiological protection of occupational exposed medical workers reduced the eye-lens equivalent dose limit from 150 to 20 mSv per year requiring an accurate dosimetric evaluation and an increase understanding of radiation induced effects on Lens cells considering the typical scenario of occupational exposed medical operators. Indeed, it is widely accepted that genomic damage of Lens epithelial cells (LEC) is a key mechanism of cataractogenesis. However, the relationship between apoptosis and cataractogenesis is still controversial. In this study biological and physical data are combined to improve the understanding of radiation induced effects on LEC. To characterize the occupational exposure of medical workers during angiographic procedures an INNOVA 4100 (General Electric Healthcare) equipment was used (scenario A). Additional experiments were conducted using a research tube (scenario B). For both scenarios, the frequencies of binucleated cells, micronuclei, p21-positive cells were assessed with different doses and dose rates. A Monte-Carlo study was conducted using a model for the photon generation with the X-ray tubes and with the Petri dishes considering the two different scenarios (A and B) to reproduce the experimental conditions and validate the irradiation setups to the cells. The simulation results have been tallied using the Monte Carlo code MCNP6. The spectral characteristics of the different X-ray beams have been estimated. All irradiated samples showed frequencies of micronuclei and p21-positive cells higher than the unirradiated controls. Differences in frequencies increased with the delivered dose measured with Gafchromic films XR-RV3. The spectrum incident on eye lens and Petri, as estimated with MCNP6, was in good agreement in the scenario A (confirming the experimental setup), while the mean energy spectrum was higher in the scenario B. Nevertheless, the response of LEC seemed mainly related to the measured absorbed dose. No effects on viability were detected. Our results support the hypothesis that apoptosis is not responsible for cataract induced by low doses of X-ray (i.e. 25 mGy) while the induction of transient p21 may interfere with the disassembly of the nuclear envelop in differentiating LEC, leading to cataract formation. Further studies are needed to better clarify the relationship we suggested between DNA damage, transient p21 induction and the inability of LEC enucleation.

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Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22084290 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4290

Author(s):

Simonetta Pazzaglia ◽

Barbara Tanno ◽

Francesca Antonelli ◽

Paola Giardullo ◽

Gabriele Babini ◽

...

Keyword(s):

Radiation Effects ◽

Critical Role ◽

Hippocampal Neurogenesis ◽

Whole Body ◽

Potential Contribution ◽

X Rays ◽

Neurocognitive Dysfunction ◽

Post Irradiation ◽

Radiation Induced ◽

Partial Body

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.

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