Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration
Purpose: Proton irradiation is used to treat choroidal melanoma of the eye. The impact on non-malignant retinal cells is currently understudied. Therefore, we here report a mouse model to investigate the impact of proton irradiation on the retina. Methods: We performed a proton beam irradiation of 5...
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MDPI AG
2025-02-01
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| author | Anja-Maria Davids Inga-Marie Pompös Norbert Kociok Jens Heufelder Sergej Skosyrski Nadine Reichhart Antonia M. Joussen Susanne A. Wolf |
| author_facet | Anja-Maria Davids Inga-Marie Pompös Norbert Kociok Jens Heufelder Sergej Skosyrski Nadine Reichhart Antonia M. Joussen Susanne A. Wolf |
| author_sort | Anja-Maria Davids |
| collection | DOAJ |
| description | Purpose: Proton irradiation is used to treat choroidal melanoma of the eye. The impact on non-malignant retinal cells is currently understudied. Therefore, we here report a mouse model to investigate the impact of proton irradiation on the retina. Methods: We performed a proton beam irradiation of 5–15 Cobalt-Gray-Equivalent (CGE) of the eyes of female C57Bl6/J (Cx3cr1<sup>+/+</sup>), Cx3cr1<sup>gfp/+</sup> and Cx3cr1<sup>gfp/gfp</sup> mice mimicking the clinical situation and evaluated the structure, function and cellular composition of the retina up to 24 weeks after irradiation. Results: Proton beam irradiation of the eye with 15 CGE leads to cataract formation after 24 weeks without affecting the gross anatomy of the retinal vasculature as shown by Fundus imaging in all genotypes respectively. However, 10 and 15 CGE, lead to a significant decrease in NG2 positive cell numbers and all three dosages induced an increase in GFAP immunoreactivity. At 24 weeks a dosage of 15 CGE resulted in functional impairment and a decrease of NG2 positive cells in both WT and Cx3cr1 animals. Iba1 cell immunoreactivity was increased in all genotypes. However, in the Cx3cr1 animals the invasion of Iba1 cells into the deep vascular layer was partially prevented. This was accompanied by a less severe functional impairment in the irradiated Cx3cr1<sup>gfp/gfp</sup> vs. WT. Conclusions: Although the gross anatomy of the retina does not seem to be affected by proton beam irradiation, the cellular composition and retinal function changed significantly in both WT and Cx3cr1 mice reflecting the clinical situation. Moreover, cataract formation was one of the major long-term effects of irradiation. We conclude that the murine model (WT and Cx3cr1 genotype) can be used to investigate proton-beam associated side effects in vivo as well as to test prospective interventions. Moreover, the loss of Cx3cr1 seems to be partially protective. |
| format | Article |
| id | doaj-art-eec939ac37e04f838a82ebe22f4853d1 |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-eec939ac37e04f838a82ebe22f4853d12025-08-20T03:12:14ZengMDPI AGCells2073-44092025-02-0114429810.3390/cells14040298Radiation Retinopathy: Microangiopathy-Inflammation-NeurodegenerationAnja-Maria Davids0Inga-Marie Pompös1Norbert Kociok2Jens Heufelder3Sergej Skosyrski4Nadine Reichhart5Antonia M. Joussen6Susanne A. Wolf7Department of Ophthalmology, Charité–University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Ophthalmology, Charité–University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Ophthalmology, Charité–University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyBerlin Protonen am Helmholtz-Zentrum Berlin, Charité–University Medicine Berlin, 14109 Berlin, GermanyDepartment of Ophthalmology, Charité–University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Ophthalmology, Charité–University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Ophthalmology, Charité–University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Ophthalmology, Charité–University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyPurpose: Proton irradiation is used to treat choroidal melanoma of the eye. The impact on non-malignant retinal cells is currently understudied. Therefore, we here report a mouse model to investigate the impact of proton irradiation on the retina. Methods: We performed a proton beam irradiation of 5–15 Cobalt-Gray-Equivalent (CGE) of the eyes of female C57Bl6/J (Cx3cr1<sup>+/+</sup>), Cx3cr1<sup>gfp/+</sup> and Cx3cr1<sup>gfp/gfp</sup> mice mimicking the clinical situation and evaluated the structure, function and cellular composition of the retina up to 24 weeks after irradiation. Results: Proton beam irradiation of the eye with 15 CGE leads to cataract formation after 24 weeks without affecting the gross anatomy of the retinal vasculature as shown by Fundus imaging in all genotypes respectively. However, 10 and 15 CGE, lead to a significant decrease in NG2 positive cell numbers and all three dosages induced an increase in GFAP immunoreactivity. At 24 weeks a dosage of 15 CGE resulted in functional impairment and a decrease of NG2 positive cells in both WT and Cx3cr1 animals. Iba1 cell immunoreactivity was increased in all genotypes. However, in the Cx3cr1 animals the invasion of Iba1 cells into the deep vascular layer was partially prevented. This was accompanied by a less severe functional impairment in the irradiated Cx3cr1<sup>gfp/gfp</sup> vs. WT. Conclusions: Although the gross anatomy of the retina does not seem to be affected by proton beam irradiation, the cellular composition and retinal function changed significantly in both WT and Cx3cr1 mice reflecting the clinical situation. Moreover, cataract formation was one of the major long-term effects of irradiation. We conclude that the murine model (WT and Cx3cr1 genotype) can be used to investigate proton-beam associated side effects in vivo as well as to test prospective interventions. Moreover, the loss of Cx3cr1 seems to be partially protective.https://www.mdpi.com/2073-4409/14/4/298retinopathyradiationretina |
| spellingShingle | Anja-Maria Davids Inga-Marie Pompös Norbert Kociok Jens Heufelder Sergej Skosyrski Nadine Reichhart Antonia M. Joussen Susanne A. Wolf Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration Cells retinopathy radiation retina |
| title | Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration |
| title_full | Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration |
| title_fullStr | Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration |
| title_full_unstemmed | Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration |
| title_short | Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration |
| title_sort | radiation retinopathy microangiopathy inflammation neurodegeneration |
| topic | retinopathy radiation retina |
| url | https://www.mdpi.com/2073-4409/14/4/298 |
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