Generation of activated sialoadhesin-positive microglia during retinal degeneration
Generation of activated sialoadhesin-positive microglia during retinal degeneration
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DOI：
10.1167/iovs.02-0824
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发表时间：
2003-05-01
影响因子：
4.4
通讯作者：
Dick, AD
中科院分区：
文献类型：
--
作者：
Hughes, EH;Schlichtenbrede, FC;Dick, AD
目的。视网膜的视网膜实质和周围血管内含有丰富的髓源性细胞（小胶质细胞）网络。它们在炎症和神经变性期间的反应和行为在很大程度上仍不清楚。在本研究中，仔细检查了 rds 小鼠感光细胞退化过程中小胶质细胞的行为，以评估它们在感光细胞凋亡中的作用。结果可能与人类类似的退化（色素性视网膜炎）有关。方法。在疾病最活跃的阶段，使用针对巨噬细胞表面标记物、诱导型一氧化氮合酶 (iNOS) 和增殖细胞核抗原 (PCNA) 的抗体，对 8、14、16、17、19、21、30 和 40 天的 rds 和野生型 CBA 小鼠的视网膜进行免疫组织化学检查。 TUNEL用于评估光感受器凋亡。结果。在rds小鼠中，小胶质细胞原位增殖（PCNA），迁移到视网膜下间隙，并采取激活的表型。小胶质细胞数量最多出现在出生后第 21 天，即光感受器细胞凋亡峰值 (P16) 后 5 天。小胶质细胞不表达 iNOS，并且不存在硝基酪氨酸。唾液酸粘附素从 P14 开始在小胶质细胞上表达，并且在 P21 时表达量最大。结论。在视网膜变性期间，小胶质细胞被激活并表达唾液酸粘附素。光感受器凋亡和小胶质细胞反应之间的时间关系表明，小胶质细胞不负责光感受器死亡的初始波，iNOS 和硝基酪氨酸的缺失证实了这一点。唾液酸粘附素的表达可能表明血视网膜屏障的破坏，这对视网膜下基因治疗策略具有免疫意义。
PURPOSE. The retina contains a rich network of myeloid-derived cells (microglia) within the retinal parenchyma and surrounding vessels. Their response and behavior during inflammation and neurodegeneration remain largely undefined. In the present study, the behavior of microglia was closely examined during the onset of photoreceptor degeneration in the rds mouse, to assess their role in photoreceptor apoptosis. The results may have relevance to similar degeneration in humans (retinitis pigmentosa).METHODS. Retinas from rds and wild-type CBA mice aged 8, 14 16, 17, 19, 21, 30, and 40 days were examined immunohistochemically, with antibodies to macrophage cell surface markers, inducible nitric oxide synthase (iNOS), and proliferating cell nuclear antigen (PCNA), during the most active phase of the disease. TUNEL was used to assess photoreceptor apoptosis.RESULTS. In the rds mouse, microglia proliferated in situ (PCNA), migrated to the subretinal space, and adopted an activated phenotype. Maximum microglial cells occurred at postnatal day (P)21, 5 days after the peak in photoreceptor apoptosis (P16). Microglia did not express iNOS, and nitrotyrosine was absent. Sialoadhesin was expressed on microglia from P14, and expression was greatest at P21.CONCLUSIONS. During retinal degeneration, microglia are activated and express sialoadhesin. The temporal relationship between photoreceptor apoptosis and microglial response suggests that microglia are not responsible for the initial wave of photoreceptor death, and this is corroborated by the absence of iNOS and nitrotyrosine. Expression of sialoadhesin may indicate blood-retinal barrier breakdown, which has immune implications for subretinal gene therapeutic strategies.