MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models

IntroductionLaser-induced photodamage is a robust method for investigating retinal pathologies in small animals. However, aiming of the photocoagulation laser is often limited by manual alignment and lacks real-time feedback on lesion location and severity. Here, we demonstrate MURIN: MUltimodal Ret...

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Main Authors: Jose J. Rico-Jimenez, Joel Jovanovic, Stephanie L. Nolen, Joseph D. Malone, Gopikrishna M. Rao, Edward M. Levine, Yuankai K. Tao
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Ophthalmology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fopht.2023.1141070/full
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author Jose J. Rico-Jimenez
Joel Jovanovic
Joel Jovanovic
Joel Jovanovic
Stephanie L. Nolen
Joseph D. Malone
Gopikrishna M. Rao
Edward M. Levine
Edward M. Levine
Edward M. Levine
Yuankai K. Tao
Yuankai K. Tao
Yuankai K. Tao
author_facet Jose J. Rico-Jimenez
Joel Jovanovic
Joel Jovanovic
Joel Jovanovic
Stephanie L. Nolen
Joseph D. Malone
Gopikrishna M. Rao
Edward M. Levine
Edward M. Levine
Edward M. Levine
Yuankai K. Tao
Yuankai K. Tao
Yuankai K. Tao
author_sort Jose J. Rico-Jimenez
collection DOAJ
description IntroductionLaser-induced photodamage is a robust method for investigating retinal pathologies in small animals. However, aiming of the photocoagulation laser is often limited by manual alignment and lacks real-time feedback on lesion location and severity. Here, we demonstrate MURIN: MUltimodal Retinal Imaging and Navigated-laser-delivery, a multimodality OCT and SLO ophthalmic imaging system with an image-guided scanning laser lesioning module optimized for the murine retina. The proposed system enables targeting of focal and extended area lesions under OCT guidance to benefit visualization of photodamage response and the precision and repeatability of laser lesion models of retinal injury.MethodsMURIN optics were optimized for simultaneous near-infrared and visible wavelength imaging/laser lesioning. Custom LabView control software was developed to steer the photocoagulation laser and automatically deliver laser pulses to targets-of-interest. In vivo retinal imaging was performed in transgenic Müller glia-tdTomato reporter mice (Rlbp1:CreER; Rosaai14, 5 animals, 10 eyes) and microglia-GFP/Müller glia-tdTomato reporter mice (Cx3cr1GFP; Rlbp1:CreER; Rosaai14, 9 animals, 15 eyes) to visualize cellular changes in the retina after laser lesion delivery.ResultsReal-time MURIN imaging concurrent with laser lesioning allowed us to visualize lesion formation dynamics and any corresponding changes in retinal morphology. We observe increasing fluorescence photoconversion on SLO and scattering contrast on OCT. Significant morphological changes are visible on MURIN after high-severity photodamage. OCT cross-sections show the spatial extent of the lesions contract over time from diffusion areas of increased scattering to granular scatterers and corresponding SLO images show a radial pattern surrounding severe focal lesions, which may be a result of a change in Müller cell shape or orientation in response to injury. The inner plexiform layer is distorted and increased RPE thickness and scattering are observed, all of which are confirmed on corresponding hematoxylin and eosin (H&E) histology and differential interference contrast (DIC) microscopy.DiscussionMURIN as a unique imaging platform that enables combined SLO and OCT imaging with an integrated image-guided laser lesioning module. This technology has clear benefits over existing multimodal imaging and laser lesioning systems by enabling simultaneous multimodal imaging, independent and precise control of Iridex laser pulse parameters and patterns, and real-time OCT and SLO visualization of lesion formation.
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spelling doaj.art-fca72cfa479e4dbd8b901948b2529a432023-04-06T04:40:31ZengFrontiers Media S.A.Frontiers in Ophthalmology2674-08262023-04-01310.3389/fopht.2023.11410701141070MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine modelsJose J. Rico-Jimenez0Joel Jovanovic1Joel Jovanovic2Joel Jovanovic3Stephanie L. Nolen4Joseph D. Malone5Gopikrishna M. Rao6Edward M. Levine7Edward M. Levine8Edward M. Levine9Yuankai K. Tao10Yuankai K. Tao11Yuankai K. Tao12Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United StatesVanderbilt University Medical Center, Vanderbilt Eye Institute, Nashville, TN, United StatesDeparment of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, United StatesDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United StatesDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, United StatesDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, United StatesDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, United StatesVanderbilt University Medical Center, Vanderbilt Eye Institute, Nashville, TN, United StatesDeparment of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, United StatesDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United StatesDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, United StatesVanderbilt University Medical Center, Vanderbilt Eye Institute, Nashville, TN, United StatesDeparment of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, United StatesIntroductionLaser-induced photodamage is a robust method for investigating retinal pathologies in small animals. However, aiming of the photocoagulation laser is often limited by manual alignment and lacks real-time feedback on lesion location and severity. Here, we demonstrate MURIN: MUltimodal Retinal Imaging and Navigated-laser-delivery, a multimodality OCT and SLO ophthalmic imaging system with an image-guided scanning laser lesioning module optimized for the murine retina. The proposed system enables targeting of focal and extended area lesions under OCT guidance to benefit visualization of photodamage response and the precision and repeatability of laser lesion models of retinal injury.MethodsMURIN optics were optimized for simultaneous near-infrared and visible wavelength imaging/laser lesioning. Custom LabView control software was developed to steer the photocoagulation laser and automatically deliver laser pulses to targets-of-interest. In vivo retinal imaging was performed in transgenic Müller glia-tdTomato reporter mice (Rlbp1:CreER; Rosaai14, 5 animals, 10 eyes) and microglia-GFP/Müller glia-tdTomato reporter mice (Cx3cr1GFP; Rlbp1:CreER; Rosaai14, 9 animals, 15 eyes) to visualize cellular changes in the retina after laser lesion delivery.ResultsReal-time MURIN imaging concurrent with laser lesioning allowed us to visualize lesion formation dynamics and any corresponding changes in retinal morphology. We observe increasing fluorescence photoconversion on SLO and scattering contrast on OCT. Significant morphological changes are visible on MURIN after high-severity photodamage. OCT cross-sections show the spatial extent of the lesions contract over time from diffusion areas of increased scattering to granular scatterers and corresponding SLO images show a radial pattern surrounding severe focal lesions, which may be a result of a change in Müller cell shape or orientation in response to injury. The inner plexiform layer is distorted and increased RPE thickness and scattering are observed, all of which are confirmed on corresponding hematoxylin and eosin (H&E) histology and differential interference contrast (DIC) microscopy.DiscussionMURIN as a unique imaging platform that enables combined SLO and OCT imaging with an integrated image-guided laser lesioning module. This technology has clear benefits over existing multimodal imaging and laser lesioning systems by enabling simultaneous multimodal imaging, independent and precise control of Iridex laser pulse parameters and patterns, and real-time OCT and SLO visualization of lesion formation.https://www.frontiersin.org/articles/10.3389/fopht.2023.1141070/fullophthalmic imagingoptical coherence tomographyscanning laser ophthalmoscopyfluorescencephotodamage
spellingShingle Jose J. Rico-Jimenez
Joel Jovanovic
Joel Jovanovic
Joel Jovanovic
Stephanie L. Nolen
Joseph D. Malone
Gopikrishna M. Rao
Edward M. Levine
Edward M. Levine
Edward M. Levine
Yuankai K. Tao
Yuankai K. Tao
Yuankai K. Tao
MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models
Frontiers in Ophthalmology
ophthalmic imaging
optical coherence tomography
scanning laser ophthalmoscopy
fluorescence
photodamage
title MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models
title_full MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models
title_fullStr MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models
title_full_unstemmed MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models
title_short MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models
title_sort murin multimodal retinal imaging and navigated laser delivery for dynamic and longitudinal tracking of photodamage in murine models
topic ophthalmic imaging
optical coherence tomography
scanning laser ophthalmoscopy
fluorescence
photodamage
url https://www.frontiersin.org/articles/10.3389/fopht.2023.1141070/full
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