کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6196233 1602572 2016 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Retinal remodeling in human retinitis pigmentosa
ترجمه فارسی عنوان
بازسازی مجدد شبکیه در رنگدانه رتینیت انسانی
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی و میکروب شناسی (عمومی)
چکیده انگلیسی


• Demonstrate advanced negative plasticity and remodeling in human retinitis pigmentosa (RP) prior to photoreceptor loss.
• Alterations in both small molecule and protein signatures of neurons and glia.
• Müller cells are the first cells to show metabolic stress in retina and the last cells left in degenerate retina.
• Retinal network topologies are altered in RP.
• Unless we understand the mechanisms of retinal degeneration, interventions designed to rescue vision loss will likely fail.

Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 150, September 2016, Pages 149–165