Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration

Area of Science:

• Ophthalmology
• Radiation Oncology
• Neuroscience

Background:

• Proton irradiation is a standard treatment for choroidal melanoma.
• The effects of proton irradiation on non-malignant retinal cells are not well understood.
• Developing reliable animal models is crucial for studying these effects.

Purpose of the Study:

• To establish a mouse model for investigating the impact of proton irradiation on the retina.
• To evaluate structural, functional, and cellular changes in the retina post-irradiation.
• To compare responses in wild-type (WT) and Cx3cr1-deficient mice.

Main Methods:

• Proton beam irradiation (5-15 CGE) was applied to the eyes of C57Bl6/J (WT), Cx3cr1^gfp/+, and Cx3cr1^gfp/gfp mice.
• Retinal structure, function, and cellular composition were assessed up to 24 weeks post-irradiation.
• Fundus imaging, NG2, GFAP, and Iba1 immunoreactivity were analyzed.

Main Results:

• 15 CGE proton irradiation induced cataract formation by 24 weeks.
• Significant decreases in NG2-positive cells and increases in GFAP immunoreactivity were observed at 10 and 15 CGE.
• Functional impairment and decreased NG2 cells occurred at 15 CGE; Iba1 cell increase was noted, but invasion was reduced in Cx3cr1 mice, correlating with less functional impairment.

Conclusions:

• Proton beam irradiation significantly alters retinal cellular composition and function, with cataract formation as a major long-term effect.
• The developed murine model (WT and Cx3cr1 genotypes) is suitable for studying proton-beam associated side effects and testing interventions.
• Loss of Cx3cr1 appears to provide partial protection against radiation-induced retinal damage and functional impairment.