Autophagic dysregulation in glaucomatous trabecular meshwork cells.
Autophagic dysregulation in glaucomatous trabecular meshwork cells.
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DOI：
10.1016/j.bbadis.2014.11.021
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发表时间：
2015-03
影响因子：
6.2
通讯作者：
Liton, Paloma B.
中科院分区：
文献类型：
--
作者：
Porter, Kristine;Hirt, Joshua;Stamer, W. Daniel;Liton, Paloma B.
原发性开角型青光眼（Primary open angle glaucoma，POAG）是一种常见的与年龄和眼内压升高相关的退行性疾病。对通过小梁网（TM）流出的房水（AH）的较高阻力导致POAG的IOP升高;不幸的是，导致阻力升高的潜在分子机制尚不清楚。然而，人们普遍认为正常组织和POAG TM组织之间的差异可能是细胞功能障碍的结果。在这里，我们研究了自噬功能和慢性氧化应激反应的TM细胞分离自青光眼和年龄匹配的供体眼睛。青光眼TM细胞显示衰老相关β-半乳糖苷酶（SA-β-Gal）和细胞脂褐素升高，连同LC 3B-II的稳态水平降低、pRPS 6 K-T389的水平降低和长寿蛋白的蛋白水解降低。此外，当暴露于高氧条件时，昏迷培养物未能激活自噬。这些结果强烈表明，mTOR依赖性失调的自噬途径的细胞分离自昏迷TM。这种失调的自噬能力可能对流出途径组织（即机械转导）具有不利影响，因此代表了促成疾病进展的重要因素。
Primary open angle glaucoma (POAG) is a degenerative disease commonly associated with aging and elevated intraocular pressure (IOP). Higher resistance to aqueous humor (AH) outflow through the trabecular meshwork (TM) generates the elevated IOP in POAG; unfortunately the underlying molecular mechanisms responsible for elevated resistance are unknown. It is widely accepted, however, that differences between normal and POAG TM tissues are presumably a consequence of cellular dysfunction. Here, we investigated the autophagic function and response to chronic oxidative stress in TM cells isolated from glaucomatous and age-matched donor eyes. Glaucomatous TM cells showed elevated senescence-associated-beta-galactosidase (SA-β-Gal) and cellular lipofuscin, together with decreased steady-state levels of LC3B-II, decreased levels of pRPS6K-T389 and reduced proteolysis of long-live proteins. Moreover, the glaucomatous cultures failed to activate autophagy when exposed to hyperoxic conditions. These results strongly suggest mTORdependent dysregulation of the autophagic pathway in cells isolated from the glaucomatous TM. Such dysregulated autophagic capacity can have a detrimental impact in outflow pathway tissue, i.e mechanotransduction, and thus represent an important factor contributing to the progression of the disease.
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影响因子：
3.9
作者：
Gerland, LM;Peyrol, S;Ffrench, M
通讯作者：
Ffrench, M
影响因子：
3.9
作者：
Liton, PB;Challa, P;Gonzalez, P
通讯作者：
Gonzalez, P
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
5.9
作者：
Izzotti, A;Saccà, SC;De Flora, S
通讯作者：
De Flora, S
影响因子：
13.3
作者：
Porter K;Nallathambi J;Lin Y;Liton PB
通讯作者：
Liton PB