定量眼底自发荧光在衰老和年龄相关性玻璃膜疣的恒河猴模型中的应用。
Quantitative Fundus Autofluorescence in Rhesus Macaques in Aging and Age-Related Drusen.
机构信息
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出版信息
Invest Ophthalmol Vis Sci. 2020 Jul 1;61(8):16. doi: 10.1167/iovs.61.8.16.
PURPOSE
To employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD).
METHODS
The qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 ± 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectral-domain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis.
RESULTS
Mean qAF levels increased with age (P < 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with age-matched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P < 0.001), with larger drusen appearing more hyperautofluorescent (R2 = 0.391, P < 0.001).
CONCLUSIONS
In rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.
目的
利用定量眼底自发荧光（qAF）成像技术，无创性评估恒河猴的视网膜色素上皮（RPE）脂褐素，作为衰老和年龄相关性黄斑变性（AMD）的非人灵长类动物（NHP）模型。
方法
使用共焦扫描激光检眼镜对 26 只恒河猴的眼睛进行 qAF 成像（平均年龄 18.8 ± 8.2 岁，范围 4-27 岁），这些眼睛的眼底外观正常或存在与年龄相关的软性玻璃膜疣，使用 488nm 激发和内部荧光参考。有软性玻璃膜疣的眼睛还进行了光谱域光学相干断层扫描成像，以测量玻璃膜疣体积和单个玻璃膜疣病变的高度。使用 Delori 网格从旁中心环形区（定量自发荧光 8 [qAF8]）测量 qAF 水平，以及在该区域内对单个玻璃膜疣病变进行局部测量。使用多变量回归分析确定 qAF 水平与年龄、性别以及玻璃膜疣的存在和体积之间的关系。
结果
平均 qAF 水平随年龄增加而升高（P < 0.001），女性更高（P = 0.047）。与年龄匹配的正常眼相比，有软性玻璃膜疣的眼的平均 qAF 水平降低（P = 0.003），玻璃膜疣体积越大，qAF 水平越低呈趋势。然而，qAF 水平在大多数单个玻璃膜疣上呈局部增加（P < 0.001），较大的玻璃膜疣呈现更明显的强荧光（R2 = 0.391，P < 0.001）。
结论
在恒河猴中，qAF 水平随年龄和性别增加而增加，但在有软性玻璃膜疣的眼中降低，与人类 AMD 相似。然而，与人类不同，玻璃膜疣病变呈强荧光，提示人类和 NHP 之间的 RPE 脂褐素存在相似和不同之处，这可能为玻璃膜疣的生物发生和 AMD 的发病机制提供深入了解。
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