title: Low-dose-rate, low-dose irradiation delays neurodegeneration in a model of retinitis pigmentosa.
abstract: The existence of radiation hormesis is controversial. Several stimulatory effects of low-dose (LD) radiation have been reported to date; however, the effects on neural tissue or neurodegeneration remain unknown. Here, we show that LD radiation has a neuroprotective effect in mouse models of retinitis pigmentosa, a hereditary, progressive neurodegenerative disease that leads to blindness. Various LD radiation doses were administered to the eyes in a retinal degeneration mouse model, and their pathological and physiological effects were analyzed. LD gamma radiation in a low-dose-rate (LDR) condition rescues photoreceptor cell apoptosis both morphologically and functionally. The greatest effect was observed in a condition using 650 mGy irradiation and a 26 mGy/minute dose rate. Multiple rounds of irradiation strengthened this neuroprotective effect. A characteristic up-regulation (563%) of antioxidative gene peroxiredoxin-2 (Prdx2) in the LDR-LD-irradiated retina was observed compared to the sham-treated control retina. Silencing the Prdx2 using small-interfering RNA administration reduced the LDR-LD rescue effect on the photoreceptors. Our results demonstrate for the first time that LDR-LD irradiation has a biological effect in neural cells of living animals. The results support that radiation exhibits hormesis, and this effect may be applied as a novel therapeutic concept for retinitis pigmentosa and for other progressive neurodegenerative diseases regardless of the mechanism of degeneration involved.
authors.affiliation: Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan. otan@kuhp.kyoto-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.forename: Congrong
authors.initials: C
authors.lastname: Guo
authors.forename: Akio
authors.initials: A
authors.lastname: Oishi
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002452:Cell Count; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000627:therapeutic use; D059165:Hormesis / Q000528:radiation effects*; D051379:Mice; D008815:Mice, Inbred Strains; D054464:Peroxiredoxins / Q000502:physiology; D011879:Radiotherapy Dosage; D017949:Retinal Cone Photoreceptor Cells / Q000528:radiation effects; D012174:Retinitis Pigmentosa / Q000532:radiotherapy*; D015854:Up-Regulation
chemical_list: D054464:Peroxiredoxins