An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: in vivo positron emission tomography imaging of glial activation.

An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: in vivo positron emission tomography imaging of glial activation.
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DOI:
10.1371/journal.pone.0030526
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Hara H
Hara H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shimazawa M;Ito Y;Inokuchi Y;Yamanaka H;Nakanishi T;Hayashi T;Ji B;Higuchi M;Suhara T;Imamura K;Araie M;Watanabe Y;Onoe H;Hara H

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我们用正电子发射断层扫描(PET)检查了外侧膝状核(LGN)变性作为可能诊断青光眼猴青光眼的指标。用激光小梁成形术对5只食蟹猴左眼进行慢性眼压升高。在激光治疗前和治疗后4周(中度青光眼阶段),用外周型苯二氮卓类受体(PBR)的PET配体[11C]PK11195进行PET成像,检测胶质细胞的激活情况。在轻度、中度和晚期实验性青光眼阶段(根据轴突丢失程度的组织学变化进行分类),用甲酚紫或针对PBR、Iba-1(小胶质细胞标记物)和GFAP(激活的星形胶质细胞标记物)的抗体进行大脑染色。在接受激光治疗的眼睛中,在所有观察期内眼压持续升高。 = 成像显示,激光治疗后4周,双侧LGN的[11C]PK11195结合电位增加,其中同侧LGN的增加具有统计学意义(P<0.05,n PET4)。免疫组织化学染色显示接受激光治疗眼的LGN层的小胶质细胞和星形胶质细胞的双侧激活。在所有实验青光眼阶段,包括轻度青光眼阶段,接受激光治疗眼的LGN层均可观察到PBR阳性细胞,其定位与Iba-1阳性的小胶质细胞和GFAP阳性的星形胶质细胞一致。这些结果提示轻度青光眼期LGN发生了胶质细胞的激活,在单眼高眼压后的中度实验性青光眼期,用[11C]PK11195进行的PET成像可以检测到LGN的变性。因此,激活的神经胶质标记物,如LGN中的PBR,可能在青光眼的无创分子成像诊断中有用。
We examined lateral geniculate nucleus (LGN) degeneration as an indicator for possible diagnosis of glaucoma in experimental glaucoma monkeys using positron emission tomography (PET). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eyes of 5 cynomolgus monkeys. Glial cell activation was detected by PET imaging with [11C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR), before and at 4 weeks after laser treatment (moderate glaucoma stage). At mild, moderate, and advanced experimental glaucoma stages (classified by histological changes based on the extent of axonal loss), brains were stained with cresyl violet, or antibodies against PBR, Iba-1 (a microglial marker), and GFAP (an activated astrocyte marker). In laser-treated eyes, IOP was persistently elevated throughout all observation periods. PET imaging showed increased [11C]PK11195 binding potential in the bilateral LGN at 4 weeks after laser treatment; the increase in the ipsilateral LGN was statistically significant (P<0.05, n = 4). Immunostaining showed bilateral activations of microglia and astrocytes in LGN layers receiving input from the laser-treated eye. PBR-positive cells were observed in LGN layers receiving input from laser-treated eye at all experimental glaucoma stages including the mild glaucoma stage and their localization coincided with Iba-1 positive microglia and GFAP-positive astrocytes. These data suggest that glial activation occurs in the LGN at a mild glaucoma stage, and that the LGN degeneration could be detected by a PET imaging with [11C]PK11195 during the moderate experimental glaucoma stage after unilateral ocular hypertension. Therefore, activated glial markers such as PBR in the LGN may be useful in noninvasive molecular imaging for diagnosis of glaucoma.
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