Optic Nerve Head Myelin-Related Protein, GFAP, and Iba1 Alterations in Non-Human Primates With Early to Moderate Experimental Glaucoma.
Optic Nerve Head Myelin-Related Protein, GFAP, and Iba1 Alterations in Non-Human Primates With Early to Moderate Experimental Glaucoma.
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DOI：
10.1167/iovs.63.11.9
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发表时间：
2022-10-03
影响因子：
4.4
通讯作者：
Burgoyne CF
中科院分区：
文献类型：
--
作者：
Chaudhary P;Stowell C;Reynaud J;Gardiner SK;Yang H;Williams G;Williams I;Marsh-Armstrong N;Burgoyne CF
本研究的目的是检测非人灵长类动物（NHP）早期/中度实验性青光眼（EG）中视神经乳头（ONH）髓鞘碱性蛋白（MBP）、2′，3 ′-环核苷酸3′-磷酸二酯酶（CNE）、胶质细胞酸性蛋白（GFAP）和离子钙结合适配分子1（Iba 1）蛋白是否发生改变。在多聚甲醛灌注后，将来自四个NHP的对照和EG眼ONH组织石蜡包埋并连续（5 μm）垂直切片。使用亚饱和光强度对抗MBP、CNF 3、GFAP、Iba 1和核染料染色切片进行成像。对全切片图像进行分割，创建解剖结构一致的椎板（L）和椎板后（RL）区域/子区域。使用统计程序“R”中的随机效应模型比较EG与对照眼L和两个RL区域（RL 1 [1-250 µm]/RL 2 [251-500 µm]）内的强度/像素簇密度数据。EG眼视网膜神经纤维损失范围为0%至20%。在RL 1区（MBP = 31.4%，P < 0.001; CNR = 62.3%，P <0.001）和RL 2区（MBP = 19.6%，P <0.001; CNR = 56.1%，P = 0.0004），EG眼的MBP和CNR强度均降低。EG眼L区（41.6%，P < 0.001）和RL区（26.7%，RL 1和28.4%，P < 0.001）GFAP强度降低。在层流（28.2%，P = 0.03和16.6%，P = 0.008）和两个RL区域（RL 1 = 37.3%，P = 0.01和23.7%，P = 0.0002; RL 2 = 53.7%，P = 0.002和33.2%，P < 0.001），Iba 1+和NucBlue像素簇密度增加。层后髓鞘破坏发生在NHP EG的早期，可能伴随着星形胶质细胞过程标记的层和层后减少以及小胶质细胞/巨噬细胞密度的增加。这些发现的机制和治疗意义值得进一步研究。
The purpose of this study was to test if optic nerve head (ONH) myelin basic protein (MBP), 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), glial fibrillary acidic protein (GFAP), and ionized calcium binding adaptor molecule 1 (Iba1) proteins are altered in non-human primate (NHP) early/moderate experimental glaucoma (EG). Following paraformaldehyde perfusion, control and EG eye ONH tissues from four NHPs were paraffin embedded and serially (5 µm) vertically sectioned. Anti-MBP, CNPase, GFAP, Iba1, and nuclear dye-stained sections were imaged using sub-saturating light intensities. Whole-section images were segmented creating anatomically consistent laminar (L) and retrolaminar (RL) regions/sub-regions. EG versus control eye intensity/pixel-cluster density data within L and two RL regions (RL1 [1-250 µm]/RL2 [251-500 µm] from L) were compared using random effects models within the statistical program “R.” EG eye retinal nerve fiber loss ranged from 0% to 20%. EG eyes’ MBP and CNPase intensity were decreased within the RL1 (MBP = 31.4%, P < 0.001; CNPase =62.3%, P < 0.001) and RL2 (MBP = 19.6%, P < 0.001; CNPase = 56.1%, P = 0.0004) regions. EG eye GFAP intensity was decreased in the L (41.6%, P < 0.001) and RL regions (26.7% for RL1, and 28.4% for RL2, both P < 0.001). Iba1+ and NucBlue pixel-cluster density were increased in the laminar (28.2%, P = 0.03 and 16.6%, P = 0.008) and both RL regions (RL1 = 37.3%, P = 0.01 and 23.7%, P = 0.0002; RL2 = 53.7%, P = 0.002 and 33.2%, P < 0.001). Retrolaminar myelin disruption occurs early in NHP EG and may be accompanied by laminar and retrolaminar decreases in astrocyte process labeling and increases in microglial/ macrophage density. The mechanistic and therapeutic implications of these findings warrant further study.
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影响因子：
4.4
作者：
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