Mao X W, Crapo J D, Mekonnen T, Lindsey N, Martinez P, Gridley D S, Slater J M
Department of Radiation Medicine, Molecular Radiation Biology Laboratories, Loma Linda University and Medical Center, Loma Linda, California, USA.
Curr Eye Res. 2009 Jan;34(1):62-72. doi: 10.1080/02713680802546948.
The purpose of this study was to evaluate the efficacy of the antioxidant Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) in protecting ocular tissue and retinal microvasculature from radiation damage.
75 rats were treated with Mn TE-2-PyP at 2.5 micro g/injection into one eye an hour before proton irradiation. The radiation was delivered in a single fraction to total doses of 8 Gray (Gy) or 28 Gy; Rats were sacrificed 3 days and 3, 6, 9, and 12 months thereafter for histology and quantification of photoreceptor cell populations and retinal capillary changes.
By 6 months following radiation, there was significant loss of retinal outer and inner nuclear layers in eyes receiving radiation only (8 and 28 Gy) (p < 0.05) compared to their controls and to the eyes of rats treated with radiation plus metalloporphyrin. Retinal microvessel length density decreased significantly 6 months following 28 Gy (p < 0.05) compared to their controls and to MnTE-2-PyP treated rats. By 12 months following irradiation, irradiated eyes showed extensive damage to the photoreceptor layer, whereas the eyes of animals receiving radiation plus MnTE-2-PyP showed almost no morphological damage. MnTE-2-PyP treatment also suppressed radiation-induced apoptosis in our study.
These results demonstrated that MnTE-2-PyP protected both photoreceptors and retinal capillaries from radiation damage, suggesting that this metalloporphyrin antioxidant is effective in regulating the damage induced by proton radiation.
本研究旨在评估抗氧化剂四(N-乙基吡啶-2-基)卟啉锰(III)(MnTE-2-PyP)在保护眼组织和视网膜微血管免受辐射损伤方面的疗效。
75只大鼠在质子照射前1小时,以2.5微克/注射量向一只眼睛注射Mn TE-2-PyP。单次给予8格雷(Gy)或28 Gy的总剂量辐射;此后3天以及3、6、9和12个月处死大鼠,进行组织学检查以及对光感受器细胞群体和视网膜毛细血管变化进行定量分析。
与对照组以及接受辐射加金属卟啉治疗的大鼠眼睛相比,仅接受辐射(8 Gy和28 Gy)的眼睛在辐射后6个月时,视网膜外核层和内核层出现明显损失(p < 0.05)。与对照组和接受MnTE-2-PyP治疗的大鼠相比,28 Gy辐射后6个月,视网膜微血管长度密度显著降低(p < 0.05)。照射后12个月时,受照射的眼睛光感受器层出现广泛损伤,而接受辐射加MnTE-2-PyP的动物眼睛几乎没有形态学损伤。在我们的研究中,MnTE-2-PyP治疗还抑制了辐射诱导的细胞凋亡。
这些结果表明,MnTE-2-PyP可保护光感受器和视网膜毛细血管免受辐射损伤,提示这种金属卟啉抗氧化剂在调节质子辐射诱导的损伤方面有效。