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Recovery of retinal oxygenation after MEMS implant activation

Martinez, Juan Carlos and Scianmarello, Nicholas and Cook, Colin A. and Gonzalez-Calle, Alejandra and Tai, Yu-Chong and Humayun, Mark S. (2019) Recovery of retinal oxygenation after MEMS implant activation. Investigative Ophthalmology and Visual Science, 60 (9). Art. No. 3344. ISSN 0146-0404. https://resolver.caltech.edu/CaltechAUTHORS:20191031-114840016

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Abstract

Purpose: Retinal ischemia due to diabetic retinopathy or retinal vascular occlusions is the leading cause of blindness worldwide. Although, the underlying pathophysiology from each condition is different, the common end results are: inner retinal hypoxia and ischemia. Changes associated with retinal hypoxia include the simultaneous activation of different pathways including inflammatory, aerobic and anaerobic metabolic response. Supplementing intravitreal oxygen has been demonstrated as a novel option in preliminary reports. Our implantable MEMS oxygenator drivesoxygen from the sub-conjunctival space to the proximity of the inner retina. The main objective of this study is to determine the efficacy of the oxygenation therapy in an ischemic animal model. Methods: Nine eyes from six pigmented rabbits were included, split evenly between either healthy, implant-treated or non-treated groups. Retinal vein occlusion (RVO) was created in all animals from treated and non-treated groups 3 days prior to surgical implantation and activation of the oxygenator. Continuous measurements of pO2 levels were performed next to the diffuser and retinal vessels using an oxygen probe controlled by a micromanipulator and monitored under indirect ophthalmoscopy. Eyes were then enucleated and the retina was peeled off and cryogenically preserved in liquid nitrogen for subsequent analysis of protein expression. Results: RVO was confirmed in all animals immediately after the procedure and remained occluded over the experiment. Oxygenator devices were successfully implanted without complications. In the treated group, oxygen levels increased progressively after a couple of minutes of activation and remained over 15 mmHg and 100 mmHg respectively (Figure 1A). For the non-treated group, pO₂ levels did not increase at the retina or nearby the device (below 5mmHg). Changes among protein expression and ratio (upregulation on NFkB and PDH; down-regulation of HIF1a, NFkB/IKKa ratio and P-PDH/PDH ratio) were observed in the treated group (Figure 1B-C). Conclusions: The MEMS oxygenator device can be safely implanted into the eye. This study supports the feasibility of intravitreal oxygen delivery for treatment of ischemic retinal diseases through inflammatory response modulation. Future experiments will evaluate long-term efficacy.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://iovs.arvojournals.org/article.aspx?articleid=2746719&resultClick=1PublisherArticle
ORCID:
AuthorORCID
Cook, Colin A.0000-0002-6283-5105
Tai, Yu-Chong0000-0001-8529-106X
Humayun, Mark S.0000-0002-5830-5208
Additional Information:© 2019 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Issue or Number:9
Record Number:CaltechAUTHORS:20191031-114840016
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191031-114840016
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99584
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:31 Oct 2019 19:43
Last Modified:09 Mar 2020 13:18

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