Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 171 64, Stockholm, Sweden.
St. Erik Eye Hospital, 171 64, Stockholm, Sweden.
Acta Neuropathol Commun. 2022 Aug 19;10(1):118. doi: 10.1186/s40478-022-01427-3.
Neuroinflammation is recognized as a key component of neurodegenerative disease. In glaucoma, a common neurodegenerative disease and the leading cause of irreversible blindness, the evidence for neuroinflammation in patients is lacking. Animal models have demonstrated significant pro-inflammatory activation of resident glia in the retina, as well as influx of blood-derived monocytes and pro-inflammatory factors. Confirmation of this in human donor tissue has been challenging due to a lack of well-preserved and well-characterized post-mortem tissue. To address this we utilize archived, wax embedded eyes fixed immediately following enucleation from living glaucoma patients. We compared glaucoma to control eyes (enucleated for uveal melanoma where the tumor did not impact the central retina or optic nerve). We performed immunolabelling for neurodegenerative and glial markers (CD45, CD163, IBA1, GFAP, Vimentin) which were quantified by high-resolution light microscopy and image analysis in FIJI. Glaucoma eyes demonstrated significant neural loss consistent with advanced neurodegeneration. IBA1 and GFAP were significantly increased in the retina and optic nerve head of the glaucomatous eyes indicating that significant neuroinflammation had occurred which support findings in animal models. Inflammation is a treatable symptom of many diseases and as such, identification of earlier inflammatory processes in glaucoma could be important for potential future treatment options.
神经炎症被认为是神经退行性疾病的一个关键组成部分。在青光眼这种常见的神经退行性疾病和导致不可逆失明的主要原因中，缺乏患者神经炎症的证据。动物模型已经证明了视网膜内固有神经胶质的显著促炎激活，以及血液衍生的单核细胞和促炎因子的涌入。由于缺乏保存良好且特征明确的死后组织，在人类供体组织中证实这一点具有挑战性。为了解决这个问题，我们利用从活体青光眼患者眼球摘除后立即固定的存档、蜡包埋的眼睛。我们将青光眼与对照组眼睛（因脉络膜黑色素瘤而摘除，肿瘤未影响中央视网膜或视神经）进行了比较。我们对神经退行性和神经胶质标志物（CD45、CD163、IBA1、GFAP、Vimentin）进行免疫标记，并用 FIJI 中的高分辨率显微镜和图像分析进行定量。青光眼眼睛表现出与晚期神经退行性变一致的显著神经丢失。IBA1 和 GFAP 在青光眼眼睛的视网膜和视神经头中显著增加，表明发生了显著的神经炎症，这支持了动物模型的发现。炎症是许多疾病的可治疗症状，因此，在青光眼早期识别炎症过程可能对潜在的未来治疗选择很重要。
