Effects of Linear Energy Transfer on the Formation and Fate of Radiation Damage to the Photoreceptor Cell Complement of the Rabbit Retina: Implications for the Projected Manned Mission to Mars

Lett, J. T.; Williams, Gerald R.

doi:10.1007/978-1-4615-2918-7_19

Cited by 9 publications

(3 citation statements)

References 21 publications

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“…Radiation-induced cell death in neurons is now known to occur through p53-induced apoptosis [65]. This is interesting in the light of earlier results of Lett and Williams [66] where late degradation of DNA in the photoreceptor cells of rabbits exposed to Fe irradiation was observed but not with low-LET irradiation. It is difficult to judge whether evidence exists for the importance of unique effects in tissue from HZE due to the lack of experimental studies.…”

Section: Tissue Damage From Hze Ionsmentioning

confidence: 67%

Applications of amorphous track models in radiation biology

Cucinotta

Nikjoo

Goodhead

1999

Radiation and Environmental Biophysics

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The average or amorphous track model uses the response of a system to gamma-rays and the radial distribution of dose about an ion's path to describe survival and other cellular endpoints from proton, heavy ion, and neutron irradiation. This model has been used for over 30 years to successfully fit many radiobiology data sets. We review several extensions of this approach that address objections to the original model, and consider applications of interest in radiobiology and space radiation risk assessment. In the light of present views of important cellular targets, the role of target size as manifested through the relative contributions from ion-kill (intra-track) and gamma-kill (inter-track) remains a critical question in understanding the success of the amorphous track model. Several variations of the amorphous model are discussed, including ones that consider the radial distribution of event-sizes rather than average electron dose, damage clusters rather than multiple targets, and a role for repair or damage processing.

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Section: Tissue Damage From Hze Ionsmentioning

confidence: 67%

Applications of amorphous track models in radiation biology

Cucinotta

Nikjoo

Goodhead

1999

Radiation and Environmental Biophysics

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“…4 However, direct damage to the outer retina and RPE by ionizing radiation has been reported in animal and human studies, and radiation-induced choroidal damage has been described. 31–35 In our study population, the size of GA tended to correlate with that of the CNVM rather than that of radiation treatment. The mean difference in size of the original CNVM and the final area of GA in 11 eyes with GA and no recurrent CNVM was 1.1-mm increase in calculated GLD over 5.3 years, a growth that can be attributed to the natural time course of expansion of GA because of AMD as previously reported.…”

Section: Discussionmentioning

confidence: 71%

Ten-Year Follow-Up of Eyes Treated With Stereotactic Fractionated External Beam Radiation for Neovascular Age-Related Macular Degeneration

Trikha

Morse

Zawadzki

et al. 2011

Retina

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Purpose To determine the long-term effects of stereotactic fractionated external beam radiation on eyes treated for neovascular age-related macular degeneration. Methods A retrospective review of all eyes treated with stereotactic fractionated external beam radiation (20–40 Gy, 2-Gy fractions) between 1997 and 2000 was performed to identify eyes with ≥2-year follow-up for analysis. A subset was imaged prospectively using a high-resolution Fourier-domain optical coherence tomography. Results Among 94 eyes treated, 33 eyes (32 subjects) had ≥2-year follow-up information (mean follow-up, 6.2 years; range, 2–10 years). Final visual acuity ranged from 20/50 to no light perception. Final macular findings included central geographic atrophy (49%), disciform scar (30%), and active choroidal neovascular membrane (9%). Fourier-domain optical coherence tomography images of three eyes with geographic atrophy revealed photoreceptor layer loss within areas of geographic atrophy with intact retinal morphology in areas of radiation exposure outside geographic atrophy. Radiation retinopathy was suspected in 18% and confirmed by fluorescein angiography in 15%, ranging from mild to neovascular glaucoma/phthisis bulbi (2 eyes). Mean time from stereotactic fractionated external beam radiation to development of radiation retinopathy was 5.4 years (range, 1–10 years). Conclusion A moderate rate of delayed radiation retinopathy was noted in eyes with neovascular age-related macular degeneration treated with stereotactic fractionated external beam radiation. Geographic atrophy was a common finding.

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“…Our previous study also showed that there were no significant differences in retinal endothelial cell density following single or split dose with two equal dose fractions of 8–28 Gy [ 15 ]. Evaluation of DNA repair of double-strand breaks in the rabbit retina, confirms that little DNA repair for dose recovery was found in the aged rabbit retinas [ 16 , 17 ], although retinal radiosensitivity of mice may be different compared to that of rats or rabbits. Surprisingly, a higher number of TUNEL positive cells were detected in the fractionated dose group compared to that of acute single dose exposure in the ONH region.…”

Section: Discussionmentioning

confidence: 72%

Evaluating Ocular Response in the Retina and Optic Nerve Head after Single and Fractionated High-Energy Protons

Mao

Stanbouly

Jones

et al. 2021

Life

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There are serious concerns about possible late radiation damage to ocular tissue from prolonged space radiation exposure, and occupational and medical procedures. This study aimed to investigate the effects of whole-body high-energy proton exposure at a single dose on apoptosis, oxidative stress, and blood-retina barrier (BRB) integrity in the retina and optic nerve head (ONH) region and to compare these radiation-induced effects with those produced by fractionated dose. Six-month-old C57BL/6 male mice were either sham irradiated or received whole-body high energy proton irradiation at an acute single dose of 0.5 Gy or 12 equal dose fractions for a total dose of 0.5 Gy over twenty-five days. At four months following irradiation, mice were euthanized and ocular tissues were collected for histochemical analysis. Significant increases in the number of apoptotic cells were documented in the mouse retinas and ONHs that received proton radiation with a single or fractionated dose (p < 0.05). Immunochemical analysis revealed enhanced immunoreactivity for oxidative biomarker, 4-hydroxynonenal (4-HNE) in the retina and ONH following single or fractionated protons with more pronounced changes observed with a single dose of 0.5 Gy. BRB integrity was also evaluated with biomarkers of aquaporin-4 (AQP-4), a water channel protein, a tight junction (TJ) protein, Zonula occludens-1 (ZO-1), and an adhesion molecule, the platelet endothelial cell adhesion molecule-1 (PECAM-1). A significantly increased expression of AQP-4 was observed in the retina following a single dose exposure compared to controls. There was also a significant increase in the expression of PECAM-1 and a decrease in the expression of ZO-1 in the retina. These changes give a strong indication of disturbance to BRB integrity in the retina. Interestingly, there was very limited immunoreactivity of AQP-4 and ZO-1 seen in the ONH region, pointing to possible lack of BRB properties as previously reported. Our data demonstrated that exposure to proton radiation of 0.5 Gy induced oxidative stress-associated apoptosis in the retina and ONH, and changes in BRB integrity in the retina. Our study also revealed the differences in BRB biomarker distribution between these two regions. In response to radiation insults, the cellular response in the retina and ONH may be differentially regulated in acute or hyperfractionated dose schedules.

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Effects of Linear Energy Transfer on the Formation and Fate of Radiation Damage to the Photoreceptor Cell Complement of the Rabbit Retina: Implications for the Projected Manned Mission to Mars

Cited by 9 publications

References 21 publications

Applications of amorphous track models in radiation biology

Applications of amorphous track models in radiation biology

Ten-Year Follow-Up of Eyes Treated With Stereotactic Fractionated External Beam Radiation for Neovascular Age-Related Macular Degeneration

Evaluating Ocular Response in the Retina and Optic Nerve Head after Single and Fractionated High-Energy Protons

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