Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Department of Ophthalmology and Vision Sciences, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine & Pathobiology, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada; Ophthalmic Pathology Laboratory, University of Toronto, Toronto, Ontario, Canada; Department of Physics, Faculty of Science, Ryerson University, Toronto, Ontario, Canada; Institute of Biomedical Engineering, Science and Technology (iBEST), St. Michael's Hospital, Ryerson University, Toronto, Ontario, Canada; Department of Mechanical Engineering, Faculty of Engineering and Architectural Science, Ryerson University, Toronto, Ontario, Canada.
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Department of Ophthalmology and Vision Sciences, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada; Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Exp Eye Res. 2020 May;194:108029. doi: 10.1016/j.exer.2020.108029. Epub 2020 Apr 3.
We aim to determine whether lymphatic drainage from the eye changes with age. Using quantitative photoacoustic tomography, groups of young and older mice were studied in the live state. 10 CD-1 mice of 2-3 months (5M/5F) were studied in addition to 13 older mice of 12-13 months (6M/7F). In each of 23 mice, near-infrared tracer (a near-infrared dye, QC-1 conjugated with Bovine Serum Albumin) was injected into the right eye, and imaging of ipsilateral cervical lymph nodes was performed with laser pulses at 11 different wavelengths prior to and 20 min, 2, 4 and 6 h after injection. Mean pixel intensities (MPIs) of nodes were calculated at each imaging session. The areas under the curves (AUC) were calculated for both groups of mice and compared using the t-test. The slopes of MPI of each region of interest were compared using the linear mixed model before and after adjusting for sex, body weight and intraocular pressure of the right eye. The mean intraocular pressure of right eyes before injection was similar in older and younger groups (12.77 ± 2.01 mmHg and 12.90 ± 2.38 mmHg, respectively; p = 0.888). In each mouse, the photoacoustic signal was detected in the right cervical lymph nodes at the 2-h time point following tracer injection into the right eye. At the 4 and 6 h imaging times, a steady increase of tracer signal was observed. Areas under the curve in the right cervical nodes were decreased significantly in older mice compared to younger mice (p = 0.007). The slopes of MPI in the nodes were significantly decreased in old mice compared to young mice both before and after adjusting for sex, body weight and intraocular pressure of the right eye (p = 0.003). In conclusion, lymphatic drainage from the eye is significantly reduced in older eyes. This finding suggests that impaired lymphatic clearance of aqueous humor, proteins and antigens from the eye may contribute to age-related disease of the eye such as glaucoma and inflammatory eye disease.
我们旨在确定眼部的淋巴引流是否随年龄而变化。使用定量光声断层扫描技术，对处于活体状态的年轻和老年小鼠进行了分组研究。此外，还对 2-3 个月龄（5M/5F）的 10 只 CD-1 小鼠和 12-13 个月龄（6M/7F）的 13 只老年小鼠进行了研究。在 23 只小鼠中，每只右眼均注射近红外示踪剂（一种近红外染料，QC-1 与牛血清白蛋白偶联），在注射前和注射后 20 分钟、2 小时、4 小时和 6 小时，用激光脉冲对同侧颈部淋巴结进行成像。在每个成像时段计算节点的平均像素强度（MPI）。用 t 检验比较两组小鼠的曲线下面积（AUC）。在调整右眼性别、体重和眼内压后，用线性混合模型比较每个感兴趣区域的 MPI 斜率。在注射前，老年组和年轻组右眼的平均眼内压相似（分别为 12.77±2.01mmHg 和 12.90±2.38mmHg；p=0.888）。在每只小鼠中，在右眼注射示踪剂后 2 小时，在右侧颈部淋巴结中检测到光声信号。在 4 小时和 6 小时的成像时间点，示踪剂信号持续增加。与年轻小鼠相比，老年小鼠右侧颈部淋巴结的 AUC 显著降低（p=0.007）。在调整右眼性别、体重和眼内压后，老年小鼠的节点 MPI 斜率与年轻小鼠相比均显著降低（p=0.003）。综上所述，眼部的淋巴引流在老年眼部明显减少。这一发现表明，眼内房水、蛋白质和抗原的淋巴清除功能受损可能导致与年龄相关的眼部疾病，如青光眼和炎症性眼病。
