UV-B–Induced DNA Damage and Repair in the Mouse Lens

Mesa, Rosana; Bassnett, Steven

doi:10.1167/iovs.13-12644

Cited by 29 publications

(17 citation statements)

References 50 publications

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“…The CZ is located in the pupil space and subject to lifelong light exposure, whereas, the other zones are located in the shadow of the iris. Exposure of CZ cells to UV light has been shown to result in potentially mutagenic DNA damage (Mesa and Bassnett, 2013). If somatic mutations indeed accrue in the CZ, the number of mutant cells would be amplified during transit through the mitotically active PGZ and GZ regions.…”

Section: Model Formulationmentioning

confidence: 99%

A stochastic model of eye lens growth

Šikić

Shi

Lubura

et al. 2015

Journal of Theoretical Biology

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The size and shape of the ocular lens must be controlled with precision if light is to be focused sharply on the retina. The lifelong growth of the lens depends on the production of cells in the anterior epithelium. At the lens equator, epithelial cells differentiate into fiber cells, which are added to the surface of the existing fiber cell mass, increasing its volume and area. We developed a stochastic model relating the rates of cell proliferation and death in various regions of the lens epithelium to deposition of fiber cells and lens growth. Epithelial population dynamics were modeled as a branching process with emigration and immigration between various proliferative zones. Numerical simulations were in agreement with empirical measurements and demonstrated that, operating within the strict confines of lens geometry, a stochastic growth engine can produce the smooth and precise growth necessary for lens function.

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Section: Model Formulationmentioning

confidence: 99%

A stochastic model of eye lens growth

Šikić

Shi

Lubura

et al. 2015

Journal of Theoretical Biology

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“…Eyes have a certain capacity to resist damage; however, for cataract patients, functional defects in the defense against UV and oxidative stress may enable damage factors to cause epithelial apoptosis in the crystalline lens more easily, which may be the cytological basis underlying the formation of cataracts (3). Generally, UV exposure may lead to a series of complex acute or chronic reactions and produce a surplus reactive oxygen species, including hydrogen peroxide and peroxide ions (4,5). Degradation, cross-linking and polymerization of proteins in the crystalline lens may occur if the reactive oxygen species are not eliminated by reduction and accumulate substantially (6).…”

Section: Introductionmentioning

confidence: 99%

Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens

Dong

Zheng

Xiao

et al. 2015

Experimental and Therapeutic Medicine

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The aim of the present study was to analyze the role of Bcl-2 during the process of apoptosis in the mouse crystalline lens. In total, 12 normal mice served as the control group and 12 Bcl-2 knockout (K.O) mice served as the experimental group. The mouse crystalline lens was sampled for the detection of Bcl-2 and caspase-3 expression following exposure to ultraviolet (UV) radiation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine Bcl-2 expression in the groups of normal mice receiving UV radiation or not receiving UV radiation. Samples of the murine crystalline lens were microscopically harvested and analyzed using western blotting. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Furthermore, caspase 3 activity was examined using enzyme-linked immunosorbent assay kits, and RT-qPCR was used to analyze caspase-3 expression levels. The results of the present study demonstrated that there was no statistically significant difference in the level of Bcl-2 gene transcription between the two groups. In addition, UV radiation did not change the macrostructure of the crystalline lens in the group of normal mice or the group of Bcl-2 K.O mice. The results of the TUNEL assay indicated that the normal-UV group exhibited a more significant apoptosis level compared with the Bcl-2 K.O-UV group. Furthermore, the mRNA expression level of caspase-3 in the normal-UV group was significantly higher compared with the normal-nonUV group (P<0.05), while the levels in the Bcl-2 K.O-UV group were significantly higher compared with the Bcl-2 K.O and normal-nonUV groups (P<0.05). In addition, the mRNA expression level of caspase-3 was significantly higher in the normal-UV, as compared with the Bcl-2 K.O-UV group (P<0.05), and the variation trends in caspase-3 activity were consistent. In conclusion, the results of the present study demonstrated that Bcl-2 may have an important role in the promotion of UV-induced apoptosis in the crystalline lens.

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“…A major insult to the lens epithelium is UV light exposure (21)(22)(23)(24). The human cornea absorbs all incident light below 300 nm wavelength and ϳ92% of UVB between 300 and 315 nm (24,83,84).…”

Section: Discussionmentioning

confidence: 99%

“…A major consequence of UV light exposure to the lens is damage to the light-facing monolayer of anterior epithelial cells (21)(22)(23)(24)) that overlie and are required for the homeostasis of the organelle-free fiber cells that make up the lens core (11,25,26). UV light exposure has been shown to result in apoptosis of lens epithelial cells (21,22,(27)(28)(29), and damage to lens epithelial cells and their subcellular components results in cataract formation (22, 24, 30 -32).…”

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confidence: 99%

Integrin αVβ5-mediated Removal of Apoptotic Cell Debris by the Eye Lens and Its Inhibition by UV Light Exposure

Chauss

Brennan

Бакина

et al. 2015

Journal of Biological Chemistry

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Accumulation of apoptotic material is toxic and associated with cataract and other disease states. Identification of mechanisms that prevent accumulation of apoptotic debris is important for establishing the etiology of these diseases. The ocular lens is routinely assaulted by UV light that causes lens cell apoptosis and is associated with cataract formation. To date, no molecular mechanism for removal of toxic apoptotic debris has been identified in the lens. Vesicular debris within lens cells exposed to UV light has been observed raising speculation that lens cells themselves could act as phagocytes to remove toxic apoptotic debris. However, phagocytosis has not been confirmed as a function of the intact eye lens, and no mechanism for lens phagocytosis has been established. Here, we demonstrate that the eye lens is capable of phagocytizing extracellular lens cell debris. Using high throughput RNA sequencing and bioinformatics analysis, we establish that lens epithelial cells express members of the integrin ␣V␤5-mediated phagocytosis pathway and that internalized cell debris co-localizes with ␣V␤5 and with RAB7 and Rab-interacting lysosomal protein that are required for phagosome maturation and fusion with lysosomes. We demonstrate that the ␣V␤5 receptor is required for lens epithelial cell phagocytosis and that UV light treatment of lens epithelial cells results in damage to the ␣V␤5 receptor with concomitant loss of phagocytosis. These data suggest that loss of ␣V␤5-mediated phagocytosis by the eye lens could result in accumulation of toxic cell debris that could contribute to UV light-induced cataract formation.

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UV-B–Induced DNA Damage and Repair in the Mouse Lens

Cited by 29 publications

References 50 publications

A stochastic model of eye lens growth

A stochastic model of eye lens growth

Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens

Integrin αVβ5-mediated Removal of Apoptotic Cell Debris by the Eye Lens and Its Inhibition by UV Light Exposure

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