Multimodal imaging and functional analysis of the chick NMDA retinal damage model.

<h4>Objectives</h4>The chick is rapidly becoming a standardized preclinical model in vision research to study mechanisms of ocular disease. We seek to comprehensively evaluate the N-methyl-D-aspartate (NMDA) model of excitotoxic retinal damage using multimodal imaging, functional, and hi...

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Autores principales:	Tyler Heisler-Taylor, Richard Wan, Elizabeth G Urbanski, Sumaya Hamadmad, Mohd Hussain Shah, Hailey Wilson, Julie Racine, Colleen M Cebulla
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d4a2f49ddb6a456998e93fcebae605cc
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spelling	oai:doaj.org-article:d4a2f49ddb6a456998e93fcebae605cc2021-12-02T20:14:47ZMultimodal imaging and functional analysis of the chick NMDA retinal damage model.1932-620310.1371/journal.pone.0257148https://doaj.org/article/d4a2f49ddb6a456998e93fcebae605cc2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257148https://doaj.org/toc/1932-6203<h4>Objectives</h4>The chick is rapidly becoming a standardized preclinical model in vision research to study mechanisms of ocular disease. We seek to comprehensively evaluate the N-methyl-D-aspartate (NMDA) model of excitotoxic retinal damage using multimodal imaging, functional, and histologic approaches in NMDA-damaged, vehicle-treated, and undamaged chicks.<h4>Methods</h4>Chicks were either left undamaged in both eyes or were injected with NMDA in the left eye and saline (vehicle) in the right eye. TUNEL assay was performed on chicks to assess levels of retinal cell death one day post-injection of NMDA or saline and on age-matched untreated chicks. Spectral domain optical coherence tomography (SD-OCT) was performed weekly on chicks and age-matched controls day 1 (D1) up to D28 post-injection. Light adapted electroretinograms (ERG) were performed alongside SD-OCT measurements on post-injection chicks along with age-matched untreated controls.<h4>Results</h4>Untreated and vehicle-treated eyes had no TUNEL positive cells while NMDA-treated eyes accumulated large numbers of TUNEL positive cells in the Inner Nuclear Layer (INL), but not other layers, at D1 post injection. Significant inner retina swelling or edema was found on SD-OCT imaging at D1 post-injection which resolved at subsequent timepoints. Both the INL and the inner plexiform layer significantly thinned by one-week post-injection and did not recover for the duration of the measurements. On ERG, NMDA-treated eyes had significantly reduced amplitudes of all parameters at D1 with all metrics improving over time. The b-wave, oscillatory potentials, and ON/OFF bipolar responses were the most affected with at least 70% reduction immediately after damage compared to the fellow eye control.<h4>Conclusion</h4>This study establishes a normative baseline on the retinal health and gross functional ability as well as intraocular pressures of undamaged, vehicle-treated, and NMDA-damaged chicks to provide a standard for comparing therapeutic treatment studies in this important animal model.Tyler Heisler-TaylorRichard WanElizabeth G UrbanskiSumaya HamadmadMohd Hussain ShahHailey WilsonJulie RacineColleen M CebullaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257148 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tyler Heisler-Taylor Richard Wan Elizabeth G Urbanski Sumaya Hamadmad Mohd Hussain Shah Hailey Wilson Julie Racine Colleen M Cebulla Multimodal imaging and functional analysis of the chick NMDA retinal damage model.
description	<h4>Objectives</h4>The chick is rapidly becoming a standardized preclinical model in vision research to study mechanisms of ocular disease. We seek to comprehensively evaluate the N-methyl-D-aspartate (NMDA) model of excitotoxic retinal damage using multimodal imaging, functional, and histologic approaches in NMDA-damaged, vehicle-treated, and undamaged chicks.<h4>Methods</h4>Chicks were either left undamaged in both eyes or were injected with NMDA in the left eye and saline (vehicle) in the right eye. TUNEL assay was performed on chicks to assess levels of retinal cell death one day post-injection of NMDA or saline and on age-matched untreated chicks. Spectral domain optical coherence tomography (SD-OCT) was performed weekly on chicks and age-matched controls day 1 (D1) up to D28 post-injection. Light adapted electroretinograms (ERG) were performed alongside SD-OCT measurements on post-injection chicks along with age-matched untreated controls.<h4>Results</h4>Untreated and vehicle-treated eyes had no TUNEL positive cells while NMDA-treated eyes accumulated large numbers of TUNEL positive cells in the Inner Nuclear Layer (INL), but not other layers, at D1 post injection. Significant inner retina swelling or edema was found on SD-OCT imaging at D1 post-injection which resolved at subsequent timepoints. Both the INL and the inner plexiform layer significantly thinned by one-week post-injection and did not recover for the duration of the measurements. On ERG, NMDA-treated eyes had significantly reduced amplitudes of all parameters at D1 with all metrics improving over time. The b-wave, oscillatory potentials, and ON/OFF bipolar responses were the most affected with at least 70% reduction immediately after damage compared to the fellow eye control.<h4>Conclusion</h4>This study establishes a normative baseline on the retinal health and gross functional ability as well as intraocular pressures of undamaged, vehicle-treated, and NMDA-damaged chicks to provide a standard for comparing therapeutic treatment studies in this important animal model.
format	article
author	Tyler Heisler-Taylor Richard Wan Elizabeth G Urbanski Sumaya Hamadmad Mohd Hussain Shah Hailey Wilson Julie Racine Colleen M Cebulla
author_facet	Tyler Heisler-Taylor Richard Wan Elizabeth G Urbanski Sumaya Hamadmad Mohd Hussain Shah Hailey Wilson Julie Racine Colleen M Cebulla
author_sort	Tyler Heisler-Taylor
title	Multimodal imaging and functional analysis of the chick NMDA retinal damage model.
title_short	Multimodal imaging and functional analysis of the chick NMDA retinal damage model.
title_full	Multimodal imaging and functional analysis of the chick NMDA retinal damage model.
title_fullStr	Multimodal imaging and functional analysis of the chick NMDA retinal damage model.
title_full_unstemmed	Multimodal imaging and functional analysis of the chick NMDA retinal damage model.
title_sort	multimodal imaging and functional analysis of the chick nmda retinal damage model.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d4a2f49ddb6a456998e93fcebae605cc
work_keys_str_mv	AT tylerheislertaylor multimodalimagingandfunctionalanalysisofthechicknmdaretinaldamagemodel AT richardwan multimodalimagingandfunctionalanalysisofthechicknmdaretinaldamagemodel AT elizabethgurbanski multimodalimagingandfunctionalanalysisofthechicknmdaretinaldamagemodel AT sumayahamadmad multimodalimagingandfunctionalanalysisofthechicknmdaretinaldamagemodel AT mohdhussainshah multimodalimagingandfunctionalanalysisofthechicknmdaretinaldamagemodel AT haileywilson multimodalimagingandfunctionalanalysisofthechicknmdaretinaldamagemodel AT julieracine multimodalimagingandfunctionalanalysisofthechicknmdaretinaldamagemodel AT colleenmcebulla multimodalimagingandfunctionalanalysisofthechicknmdaretinaldamagemodel
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Multimodal imaging and functional analysis of the chick NMDA retinal damage model.

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