University of Iowa, Department of Ophthalmology and Visual Sciences, Iowa City, Iowa, United States.
Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care System, Iowa City, Iowa, United States.
Invest Ophthalmol Vis Sci. 2020 Dec 1;61(14):18. doi: 10.1167/iovs.61.14.18.
We previously demonstrated that passive transfer of lymphocytes from glaucomatous mice induces retinal ganglion cell (RGC) damage in recipient animals, suggesting a role for immune responses in the multifactorial pathophysiology of glaucoma. Here we evaluate whether absence of an adaptive immune response reduces RGC loss in glaucoma.
Elevated intraocular pressure (IOP) was induced in one eye of C57BL/6J (B6) or T- and B-cell-deficient Rag1-/- knockout mice. After 16 weeks RGC density was determined in both the induced and the normotensive contralateral eyes. Data were compared to mice having received injections of "empty" vector (controls). The number of extravascular CD3+ cells in the retinas was determined using FACS.
Retinas of eyes with elevated IOP contain significantly more extravasated CD3+ cells than control retinas (46.0 vs. 27.1, P = 0.025). After 16 weeks of elevated IOP the average RGC density in B6 mice decreased by 20.7% (P = 1.9 × 10-4). In contrast, RGC loss in Rag1-/- eyes with elevated IOP was significantly lower (10.3%, P = 0.006 vs. B6). RGC loss was also observed in the contralateral eyes of B6 mice, despite the absence of elevated IOP in those eyes (10.1%; P = 0.008). In RAG1-/- loss in the contralateral eyes was minimal (3.1%) and significantly below that detected in B6 (P = 0.02).
Our findings demonstrate that T Rag1-/- mice are significantly protected from glaucomatous RGC loss. In this model, lymphocyte activity contributes to approximately half of all RGC loss in eyes with elevated IOP and to essentially all loss observed in normotensive contralateral eyes.
我们之前的研究表明，从青光眼小鼠中被动转移淋巴细胞会导致受者动物的视网膜神经节细胞（RGC）损伤，这表明免疫反应在青光眼的多因素病理生理学中起作用。在这里，我们评估适应性免疫反应缺失是否会减少青光眼的 RGC 损失。
在 C57BL/6J（B6）或 T 和 B 细胞缺陷 Rag1-/- 敲除小鼠的一只眼中升高眼内压（IOP）。16 周后，在诱导的和正常眼压的对侧眼中确定 RGC 密度。将数据与接受“空”载体（对照）注射的小鼠进行比较。使用 FACS 确定视网膜中血管外 CD3+细胞的数量。
IOP 升高的眼睛的视网膜中含有明显更多的血管外 CD3+细胞，比对照视网膜多（46.0 对 27.1，P=0.025）。在 16 周的 IOP 升高后，B6 小鼠的平均 RGC 密度下降了 20.7%（P=1.9×10-4）。相比之下，Rag1-/- 小鼠的 RGC 损失在升高的 IOP 下明显较低（10.3%，P=0.006 与 B6 相比）。尽管这些眼睛中的 IOP 没有升高，但在 B6 小鼠的对侧眼中也观察到 RGC 损失（10.1%；P=0.008）。在 RAG1-/- 中，对侧眼的损失最小（3.1%），明显低于 B6 检测到的损失（P=0.02）。
我们的研究结果表明，T Rag1-/- 小鼠对青光眼性 RGC 损失有显著的保护作用。在这种模型中，淋巴细胞活性导致升高的 IOP 眼中约一半的所有 RGC 损失以及正常眼压对侧眼中观察到的所有损失。
