کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4011080 1602578 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting the ER-autophagy system in the trabecular meshwork to treat glaucoma
ترجمه فارسی عنوان
هدف قرار دادن سیستم ER ـ اتوفاژی در شبکه ترابکولار برای درمان گلوکوم
کلمات کلیدی
Myocilin؛ گلوکوم یا آب سیاه؛ شبکه ترابکولار؛ Grp94؛ اتوفاژی
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی و میکروب شناسی (عمومی)
چکیده انگلیسی


• Mutations in the MYOC gene lead to intra-ER protein accumulation and aggregation resulting in TM cell toxicity.
• Misfolded myocilin associates with Grp94, preventing autophagic degradation of aggregated protein.
• Grp94 inhibition allows misfolded myocilin aggregates to be processed and degraded through an autophagic mechanism.
• Treatment with Grp94 inhibitions in coordination with autophagic enhancers could be useful in treating glaucoma.

A major drainage network involved in aqueous humor dynamics is the conventional outflow pathway, which is gated by the trabecular meshwork (TM). The TM acts as a molecular sieve, providing resistance to aqueous outflow, which is responsible for regulating intraocular pressure (IOP). If the TM is damaged, aqueous outflow is impaired, IOP increases and glaucoma can manifest. Mutations in the MYOC gene cause hereditary primary open-angle glaucoma (POAG) by promoting the abnormal amyloidosis of the myocilin protein in the endoplasmic reticulum (ER), leading to ER stress-induced TM cell death. Myocilin accumulation is observed in approximately 70–80% of all glaucoma cases suggesting that environmental or other genetic factors may also promote myocilin toxicity. For example, simply preventing myocilin glycosylation is sufficient to promote its abnormal accretion. These myocilin amyloids are unique as there are no other known pathogenic proteins that accumulate within the ER of TM cells and cause toxicity. Moreover, this pathogenic accumulation only kills TM cells, despite expression of this protein in other cell types, suggesting that another modifier exclusive to the TM participates in the proteotoxicity of myocilin. ER autophagy (reticulophagy) is one of the pathways essential for myocilin clearance that can be impacted dramatically by aging and other environmental factors such as nutrition. This review will discuss the link between myocilin and autophagy, evaluating the role of this degradation pathway in glaucoma as well as its potential as a therapeutic target.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 144, March 2016, Pages 38–45
نویسندگان
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