Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
PLoS One. 2012;7(1):e30526. doi: 10.1371/journal.pone.0030526. Epub 2012 Jan 27.
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 [(11)C]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 [(11)C]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 [(11)C]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.
我们使用正电子发射断层扫描（PET）检查外侧膝状体核（LGN）退化，作为实验性青光眼猴青光眼可能诊断的指标。通过激光小梁成形术在 5 只食蟹猴的左眼引起慢性眼内压（IOP）升高。在激光治疗前（轻度青光眼阶段）和治疗后 4 周（中度青光眼阶段），用[11C]PK11195（外周型苯二氮䓬受体（PBR）的 PET 配体）通过 PET 成像检测神经胶质细胞激活。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分类），用 Cresyl 紫或针对 PBR、Iba-1（小胶质细胞标志物）和 GFAP（活化星形胶质细胞标志物）的抗体对大脑进行染色。在激光治疗的眼中，IOP 在整个观察期间持续升高。PET 成像显示，激光治疗后 4 周双侧 LGN 的[11C]PK11195 结合潜能增加；同侧 LGN 的增加具有统计学意义（P<0.05，n=4）。免疫染色显示，在接受激光治疗眼输入的 LGN 层中，小胶质细胞和星形胶质细胞均发生双侧激活。在包括轻度青光眼阶段在内的所有实验性青光眼阶段，均在接受激光治疗眼输入的 LGN 层中观察到 PBR 阳性细胞，其定位与 Iba-1 阳性小胶质细胞和 GFAP 阳性星形胶质细胞重合。这些数据表明，在轻度青光眼阶段，LGN 中发生神经胶质细胞激活，并且在单侧眼压升高后的中度实验性青光眼阶段，可通过[11C]PK11195 的 PET 成像检测到 LGN 变性。因此，LGN 中的激活神经胶质标志物（如 PBR）可能在青光眼的非侵入性分子成像中有用。
