Johnson Elaine C, Cepurna William O, Choi Dongseok, Choe Tiffany E, Morrison John C
The Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
The Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States Public Health & Preventive Medicine, Oregon Health & Science University, Portland, Oregon, United States.
Invest Ophthalmol Vis Sci. 2014 Dec 18;56(1):412-9. doi: 10.1167/iovs.14-15094.
Optic nerve injury has been found to be dramatically reduced in a genetic mouse glaucoma model following exposure to sublethal, head-only irradiation. In this study, the same radiation treatment was used prior to experimental induction of elevated intraocular pressure (IOP) to determine if radiation is neuroprotective in another glaucoma model.
Episcleral vein injection of hypertonic saline was used to elevate IOP unilaterally in two groups of rats: (1) otherwise untreated and (2) radiation pretreated, n > 25/group. Intraocular pressure histories were collected for 5 weeks, when optic nerves were prepared and graded for injury. Statistical analyses were used to compare IOP history and nerve injury. The density of microglia and macrophages in two nerve head regions was determined by Iba1 immunolabeling.
Mean and peak IOP elevations were not different between the two glaucoma model groups. Mean optic nerve injury grades were not different in glaucoma model optic nerves and were equivalent to approximately 35% of axons degenerating. Nerves selected for lower mean or peak IOP elevations did not differ in optic nerve injury. Similarly, nerves selected for lower injury grade did not differ in IOP exposure. By multiple regression modeling, nerve injury grade was most significantly associated with mean IOP (P < 0.002). There was no significant effect of radiation treatment. Iba1+ cell density was not altered by radiation treatment.
In contrast to previous observations in a mouse genetic glaucoma model, head-only irradiation offers the adult rat optic nerve no protection from optic nerve degeneration due to chronic, experimentally induced IOP elevation.
在一个遗传性小鼠青光眼模型中，已发现暴露于亚致死性、仅头部照射后，视神经损伤显著减少。在本研究中，在实验性诱导眼内压（IOP）升高之前采用相同的放射治疗，以确定放射在另一个青光眼模型中是否具有神经保护作用。
在两组大鼠中通过巩膜静脉注射高渗盐水单侧升高IOP：（1）未进行其他治疗的组和（2）放射预处理组，每组n>25。收集5周的眼内压病史，之后制备视神经并对损伤进行分级。采用统计分析比较眼内压病史和神经损伤情况。通过Iba1免疫标记确定两个视神经乳头区域小胶质细胞和巨噬细胞的密度。
两个青光眼模型组之间的平均和峰值IOP升高无差异。青光眼模型视神经的平均视神经损伤分级无差异，且相当于约35%的轴突发生退变。选择平均或峰值IOP升高较低的神经，其视神经损伤无差异。同样，选择损伤分级较低的神经，其IOP暴露情况无差异。通过多元回归建模，神经损伤分级与平均IOP最显著相关（P<0.002）。放射治疗无显著效果。放射治疗未改变Iba1+细胞密度。
与先前在小鼠遗传性青光眼模型中的观察结果相反，仅头部照射对成年大鼠视神经因慢性实验性诱导的IOP升高所致的视神经退变无保护作用。
