کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5704106 | 1602564 | 2017 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury
ترجمه فارسی عنوان
تجویز موضعی یک مهار کننده راک / خالص باعث افزایش بقای سلول گانگلیونی شبکیه و بازسازی آکسون پس از آسیب عصبی بینایی
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کلمات کلیدی
CTBRho-kinaseRGCiOpRegeneration - باززاییcholera toxin B - تومور مثانه BNorepinephrine transporters - حمل کننده های نوراپی نفرینNET - خالصCNS - دستگاه عصبی مرکزیretinal ganglion cell - سلول گانگلیونی شبکیهcentral nerve system - سیستم عصبی مرکزیtrabecular meshwork - شبکه مشبکOptic nerve - عصب بیناییIntraocular pressure - فشار داخل چشمGlaucoma - گلوکوم Rock - یا راک
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی و میکروب شناسی (عمومی)
چکیده انگلیسی
Intraocular pressure (IOP)-lowering ophthalmic solutions that inhibit Rho-associated protein kinases (Rock) and norepinephrine transporters (Net) are currently under clinical evaluation. Here we evaluate topical application of one such drug for its effects on retinal ganglion cell (RGC) survival and axon regeneration after optic nerve crush injury. We performed unilateral optic nerve crush on young rats (P18) and topically applied Rock/Net inhibitor AR-13324 or placebo 3 times a day for 14 days. IOP was measured starting 3 days before and up to 9 days after injury. On day 12, cholera toxin B (CTB) was injected intravitreally to trace optic nerve regeneration. On day 14, retinas and optic nerves were collected. The retinas were flat-mounted and stained with RBPMS to quantify RGC survival and the optic nerves were sectioned for optic nerve axon quantification using fluorescent and confocal microscopy. Rock phosphorylation targets implicated in axon growth including cofilin and LIMK were examined by fluorescence microscopy and quantitative western blotting. AR-13324 lowered IOP as expected. RGC survival and optic nerve axon regeneration were significantly higher with Rock/Net inhibitor treatment compared with placebo. Furthermore, topical therapy decreased Rock target protein phosphorylation in the retinas and proximal optic nerves. These data suggest that topical administration of a Rock/Net inhibitor promotes RGC survival and regeneration after optic nerve injury, with associated molecular changes indicative of posterior drug activity. Coordinated IOP lowering and neuroprotective or regenerative effects may be advantageous in the treatment of patients with glaucoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 158, May 2017, Pages 33-42
Journal: Experimental Eye Research - Volume 158, May 2017, Pages 33-42
نویسندگان
Peter X. Shaw, Alan Sang, Yan Wang, Daisy Ho, Christopher Douglas, Lara Dia, Jeffrey L. Goldberg,