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视网膜色素变性啮齿动物模型体内视网膜假体的局部信号传导。

Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model in vivo.

作者信息

Fransen James W, Pangeni Gobinda, Pardue Machelle T, McCall Maureen A

机构信息

Department of Anatomical Sciences and Neurobiology, University of Louisville, KY 40202, USA.

出版信息

J Neural Eng. 2014 Aug;11(4):046012. doi: 10.1088/1741-2560/11/4/046012. Epub 2014 Jun 18.

Abstract

OBJECTIVE

In clinical trials, retinitis pigmentosa patients implanted with a retinal prosthetic device show enhanced spatial vision, including the ability to read large text and navigate. New prosthetics aim to increase spatial resolution by decreasing pixel/electrode size and limiting current spread. To examine spatial resolution of a new prosthetic design, we characterized and compared two photovoltaic array (PVA) designs and their interaction with the retina after subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3).

APPROACH

PVAs were implanted subretinally at two stages of degeneration and assessed in vivo using extracellular recordings in the superior colliculus (SC). Several aspects of this interaction were evaluated by varying duration, irradiance and position of a near infrared laser focused on the PVA. These characteristics included: activation threshold, response linearity, SC signal topography and spatial localization. The major design difference between the two PVA designs is the inclusion of local current returns in the newer design.

MAIN RESULTS

When tested in vivo, PVA-evoked response thresholds were independent of pixel/electrode size, but differ between the new and old PVA designs. Response thresholds were independent of implantation age and duration (⩽7.5 months). For both prosthesis designs, threshold intensities were within established safety limits. PVA-evoked responses require inner retina synaptic transmission and do not directly activate retinal ganglion cells. The new PVA design evokes local retinal activation, which is not found with the older PVA design that lacks local current returns.

SIGNIFICANCE

Our study provides in vivo evidence that prosthetics make functional contacts with the inner nuclear layer at several stages of degeneration. The new PVA design enhances local activation within the retina and SC. Together these results predict that the new design can potentially harness the inherent processing within the retina and is likely to produce higher spatial resolution in patients.

摘要

目的

在临床试验中,植入视网膜假体装置的视网膜色素变性患者表现出空间视觉增强,包括阅读大字和导航的能力。新型假体旨在通过减小像素/电极尺寸并限制电流扩散来提高空间分辨率。为了研究一种新型假体设计的空间分辨率,我们对两种光伏阵列(PVA)设计进行了表征和比较,并在转基因S334ter 3系大鼠(Tg S334ter-3)视网膜下植入后研究了它们与视网膜的相互作用。

方法

在变性的两个阶段将PVA植入视网膜下,并使用上丘(SC)的细胞外记录进行体内评估。通过改变聚焦在PVA上的近红外激光的持续时间、辐照度和位置,对这种相互作用的几个方面进行了评估。这些特征包括:激活阈值、反应线性、SC信号地形图和空间定位。两种PVA设计之间的主要设计差异在于较新的设计中包含局部电流回路。

主要结果

在体内测试时,PVA诱发的反应阈值与像素/电极尺寸无关,但新旧PVA设计之间存在差异。反应阈值与植入年龄和持续时间(≤7.5个月)无关。对于两种假体设计,阈值强度均在既定的安全范围内。PVA诱发的反应需要内视网膜突触传递,不会直接激活视网膜神经节细胞。新的PVA设计会引起局部视网膜激活,而缺乏局部电流回路的旧PVA设计则不会出现这种情况。

意义

我们的研究提供了体内证据,表明假体在变性的几个阶段与内核层建立了功能性联系。新的PVA设计增强了视网膜和SC内的局部激活。这些结果共同预测,新设计可能利用视网膜内的固有处理能力,并可能在患者中产生更高的空间分辨率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/4128185/581b5aab471b/nihms608759f1.jpg

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