Anterograde transport blockade precedes deficits in retrograde transport in the visual projection of the DBA/2J mouse model of glaucoma.
Anterograde transport blockade precedes deficits in retrograde transport in the visual projection of the DBA/2J mouse model of glaucoma.
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DOI：
10.3389/fnins.2014.00290
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发表时间：
2014
影响因子：
4.3
通讯作者：
Crish SD
中科院分区：
文献类型：
--
作者：
Dengler-Crish CM;Smith MA;Inman DM;Wilson GN;Young JW;Crish SD
据报道，轴突运输缺陷是包括青光眼在内的几种神经退行性疾病的早期病理学。然而，人们对这些缺陷的进展和机制知之甚少。先前的工作表明，顺行运输比逆行运输更早受到影响，影响程度也更大，但这从未在体内直接进行过检查。使用顺行和逆行相结合的纤维束追踪方法，我们检查了青光眼前（3个月大）和青光眼（9-13个月大）DBA/2J小鼠视网膜离断投影中顺行和逆行运输缺陷的时间过程。 DBA/2J-Gpnmb+ 小鼠被用作对照品系，其视网膜神经节细胞密度与 C57BL/6J 对照小鼠（视觉研究领域常用的品系）相似。通过将霍乱毒素 B 注射到眼睛中并将 FluoroGold 注射到上丘 (SC)，我们能够测量初级视觉投影中的顺行和逆行传输。在 DBA/2J 中，9-10 个月龄组中从视网膜到 SC 的顺行传输减少了 69%，而逆行传输仅比青光眼前小鼠的水平减少了 23%。尽管略有减少，但这些青光眼年龄组的逆行运输在 13 个月大之前仍基本保持完整。这些发现表明，轴突运输缺陷发生在仍与其大脑目标相连的半功能性轴突中。由浅层 SC 中雌激素相关受体 β 标记的存在所确定的结构持久性在逆行转运发生减少的时间点后得以维持，这也支持转运缺陷可能是由于生理或功能异常而不是明显的结构损失所致。
Axonal transport deficits have been reported as an early pathology in several neurodegenerative disorders, including glaucoma. However, the progression and mechanisms of these deficits are poorly understood. Previous work suggests that anterograde transport is affected earlier and to a larger degree than retrograde transport, yet this has never been examined directly in vivo. Using combined anterograde and retrograde tract tracing methods, we examined the time-course of anterograde and retrograde transport deficits in the retinofugal projection in pre-glaucomatous (3 month-old) and glaucomatous (9–13 month old) DBA/2J mice. DBA/2J-Gpnmb+ mice were used as a control strain and were shown to have similar retinal ganglion cell densities as C57BL/6J control mice—a strain commonly investigated in the field of vision research. Using cholera toxin-B injections into the eye and FluoroGold injections into the superior colliculus (SC), we were able to measure anterograde and retrograde transport in the primary visual projection. In DBA/2J, anterograde transport from the retina to SC was decreased by 69% in the 9–10 month-old age group, while retrograde transport was only reduced by 23% from levels seen in pre-glaucomatous mice. Despite this minor reduction, retrograde transport remained largely intact in these glaucomatous age groups until 13-months of age. These findings indicate that axonal transport deficits occur in semi-functional axons that are still connected to their brain targets. Structural persistence as determined by presence of estrogen-related receptor beta label in the superficial SC was maintained beyond time-points where reductions in retrograde transport occurred, also supporting that transport deficits may be due to physiological or functional abnormalities as opposed to overt structural loss.
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影响因子：
4
作者：
Lee, Sangmook;Sunil, Neethu;Shea, Thomas B.
通讯作者：
Shea, Thomas B.
影响因子：
5.3
作者：
López-Herrera, MPL;Mayor-Torroglosa, S;Vidal-Sanz, M
通讯作者：
Vidal-Sanz, M
影响因子：
4.4
作者：
Banitt, Michael R.;Ventura, Lori M.;Porciatti, Vittorio
通讯作者：
Porciatti, Vittorio
影响因子：
5.1
作者：
Brady, Scott;Morfini, Gerardo
通讯作者：
Morfini, Gerardo
视网膜神经节细胞变性是拓扑的，但在DBA/2J小鼠中不是特异性细胞类型。
影响因子：
7.8
作者：
Jakobs, Tatjana C;Libby, Richard T;Ben, Yixin;John, Simon W M;Masland, Richard H
通讯作者：
Masland, Richard H