1.陆军军医大学(第三军医大学)第一附属医院眼科,视觉损伤与再生修复重庆市重点实验室,重庆
2.南部战区总医院眼科,广东广州
Received:27 June 2025,
Revised:2025-09-10,
Accepted:11 September 2025,
Published:15 October 2025
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敖光军,陈霞,杨君玲,等.富勒醇纳米颗粒不同给药方式对放射性视网膜损伤安全性及有效性评价[J].陆军军医大学学报,2025,47(19):2327-2339.DOI:10.16016/j.2097-0927.202506081.
AO G J,CHEN X,YANG J L,et al.Impact of various administration routes of fullerenol nanoparticles on therapeutic outcomes of radiation-induced retinal injury[J].J Army Med Univ,2025,47(19):2327-2339.DOI:10.16016/j.2097-0927.202506081.
敖光军,陈霞,杨君玲,等.富勒醇纳米颗粒不同给药方式对放射性视网膜损伤安全性及有效性评价[J].陆军军医大学学报,2025,47(19):2327-2339.DOI:10.16016/j.2097-0927.202506081. DOI:
AO G J,CHEN X,YANG J L,et al.Impact of various administration routes of fullerenol nanoparticles on therapeutic outcomes of radiation-induced retinal injury[J].J Army Med Univ,2025,47(19):2327-2339.DOI:10.16016/j.2097-0927.202506081. DOI:
目的
2
探究富勒醇纳米颗粒不同给药方式对放射性视网膜损伤治疗效果的差异及可能机制。
方法
2
将8周龄成年雄性SD大鼠按随机数字表法分为空白组(Control)、辐照组(X-Ray)、辐照+玻腔给药组[X+F(IVT)]、辐照+眼表给药组[X+F(OS)]、辐照+静脉给药组[X+F(IV)],每组5只。空白组不做处理,辐照组用X射线辐照造模,剩余组在辐照后接受不同途径的富勒醇纳米颗粒治疗,对应检测时间点分别为7、14、28 d;通过检测各组大鼠体质量及眼底改变评估药物安全性,视网膜光学相干断层扫描(optical coherence tomography, OCT)评比视网膜组织结构变化,视网膜电图(electroretinogram, ERG)和功能振荡电位(oscillatory potentials, OPs)评价视觉功能,CD31免疫荧光染色评价视网膜内皮血管状态,活体成像评价富勒醇纳米颗粒在眼部的蓄积情况。
结果
2
体质量生长曲线结果显示,富勒醇纳米颗粒不影响大鼠生长发育,给药组与对照组无统计学差异;与空白组相比,辐照组的视觉功能显著降低,视网膜电图a波、b波和OPs振幅显著下降(
P
<
0.01),OCT检测显示视网膜节细胞层(ganglion cell layer, GCL)和内核层(inner nuclear layer, INL)厚度显著增加(
P
<
0.01),同时CD31
+
细胞明显缺失(
P
<
0.01)。辐照+玻璃体腔给药组大鼠视觉功能显著改善,治疗有效维持GCL+INL厚度和挽救CD31
+
细胞缺失(
P
<
0.01),辐照+静脉给药组和辐照+眼表给药组治疗效果不明显。活体成像结果显示玻璃体腔注射能维持96 h眼部高浓度药物蓄积,眼表滴药仅能维持12 h眼部高浓度药物蓄积,静脉注射药物主要分布在血管丰富的区域,在眼部蓄积浓度低。
结论
2
富勒醇纳米颗粒对放射性视网膜损伤具有治疗作用,玻璃体腔给药组相比于眼表给药组和静脉给药组疗效更好。
Objective
2
To explore the differences in therapeutic efficacy and possible mechanism of different routes of administration of fullerene nanoparticles in the treatment of radiation retinopathy.
Methods
2
Eight-week-old adult male SD rats were randomly divided into blank group (Control)
irradiation group (X-Ray)
irradiation+vitreous cavity administration group [X+F(IVT)
]
irradiation+ocular surface administration group [X+F(OS)
]
and irradiation+intravenous administration group [X+F (IV)
]
with 5 rats in each group. The blank group was not treated
the irradiation groups exposed to X-ray irradiation to establish the model
and fullerenol nanoparticles were given to the treatment groups through different routes after irradiation. At 7
14
and 28 d after modeling
body weight and fundus changes were measured to evaluate drug safety
retinal optical coherence tomography (OCT) was used to observe the change in retinal tissue structure
and electroretinography (ERG) was applied for oscillatory potentials (OPs) to evaluate visual function. CD31 immunofluorescence staining was carried out to evaluate retinal endothelial vascular status
and i
n vivo
imaging was utilized to evaluate the accumulation of fullerenol nanoparticles in the eyes.
Results
2
The growth curves of body weight demonstrated that fullerenol nanoparticles did not affect the growth and development of rats
with no statistical difference between the treatment groups and the control group. Irradiation resulted in a significant reduction in visual function
decreased amplitudes of a-wave and b-wave
and declined OPs (
P
<
0.01)
and significantly increased thickn
esses of the ganglion cell layer (GCL) and the inner nuclear layer (INL) in the retinas
as evidenced by OCT (
P
<
0.01)
along with a notably absent presence of CD31-positive cells (
P
<
0.01). Notably
the X+F(IVT) group obtained significantly improved visual function after intravitreal administration
effectively maintained thickness of the GCL and INL
and prevention against the loss of CD31-positive cells (
P
<
0.01). However
no such effective results were observed in the irradiated groups receiving intravenous either ocular surface administration.
In vivo
imaging revealed that intravitreal administration maintained high ocular accumulation of fullerene for 96 h
while ocular surface administration sustained these concentrations for only 12 h. Intravenous administration
in contrast
only led to a predominant drug distribution in vascular-rich areas
but reduced ocular accumulation.
Conclusion
2
Fullerene nanoparticles possess a therapeutic effect on radiation retinopathy
and the intravitreal administration route demonstrates better efficacy than ocular surface and intravenous administration.
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