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Three-dimensional Imaging Coupled with Topological Quantification Uncovers Retinal Vascular Plexuses Undergoing Obliteration

Chang, Chih-Chiang and Chu, Alison and Meyer, Scott and Ding, Yichen and Sun, Michel M. and Abiri, Parinaz and Baek, Kyung In and Gudapati, Varun and Ding, Xili and Guihard, Pierre and Bostrom, Kristina I. and Li, Song and Gordon, Lynn K. and Zheng, Jie J. and Hsiai, Tzung K. (2021) Three-dimensional Imaging Coupled with Topological Quantification Uncovers Retinal Vascular Plexuses Undergoing Obliteration. Theranostics, 11 (3). pp. 1162-1175. ISSN 1838-7640. https://resolver.caltech.edu/CaltechAUTHORS:20201216-100504535

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Abstract

Introduction: Murine models provide microvascular insights into the 3-D network disarray seen in retinopathy and cardiovascular diseases. Light-sheet fluorescence microscopy (LSFM) has emerged to capture retinal vasculature in 3-D, allowing for assessment of the progression of retinopathy and the potential to screen new therapeutic targets in mice. We hereby coupled LSFM, also known as selective plane illumination microscopy, with topological quantification, to characterize the retinal vascular plexuses undergoing preferential obliteration. Method and Result: In postnatal mice, we revealed the 3-D retinal microvascular network in which the vertical sprouts bridge the primary (inner) and secondary (outer) plexuses, whereas, in an oxygen-induced retinopathy (OIR) mouse model, we demonstrated preferential obliteration of the secondary plexus and bridging vessels with a relatively unscathed primary plexus. Using clustering coefficients and Euler numbers, we computed the local versus global vascular connectivity. While local connectivity was preserved (p > 0.05, n = 5 vs. normoxia), the global vascular connectivity in hyperoxia-exposed retinas was significantly reduced (p < 0.05, n = 5 vs. normoxia). Applying principal component analysis (PCA) for auto-segmentation of the vertical sprouts, we corroborated the obliteration of the vertical sprouts bridging the secondary plexuses, as evidenced by impaired vascular branching and connectivity, and reduction in vessel volumes and lengths (p < 0.05, n = 5 vs. normoxia). Conclusion: Coupling 3-D LSFM with topological quantification uncovered the retinal vasculature undergoing hyperoxia-induced obliteration from the secondary (outer) plexus to the vertical sprouts. The use of clustering coefficients, Euler's number, and PCA provided new network insights into OIR-associated vascular obliteration, with translational significance for investigating therapeutic interventions to prevent visual impairment.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.7150/thno.53073DOIArticle
ORCID:
AuthorORCID
Ding, Yichen0000-0002-6242-3506
Abiri, Parinaz0000-0002-0520-6863
Baek, Kyung In0000-0001-9388-2070
Gudapati, Varun0000-0003-0134-7236
Hsiai, Tzung K.0000-0003-1734-0792
Additional Information:© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). Received: 2020.09.09; Accepted: 2020.10.19; Published: 2021.01.01. The present work was funded by NIH grants National Institutes of Health R01HL083015 (TKH), R01HL111437 (TKH), R01HL129727 (TKH), R01HL118650 (TKH), VA MERIT AWARD I01 BX004356 (TKH), K99 HL148493 (YD), and AHA 18CDA34110338 (YD). The authors have declared that no competing interest exists.
Funders:
Funding AgencyGrant Number
NIHR01HL083015
NIHR01HL111437
NIHR01HL129727
NIHR01HL118650
Veterans AffairsI01 BX004356
NIHK99 HL148493
American Heart Association18CDA34110338
Subject Keywords:Light-sheet fluorescence microscopy, Primary and secondary plexus, Vertical sprouts, Oxygen-induced retinopathy, Retinal vasculature
Issue or Number:3
Record Number:CaltechAUTHORS:20201216-100504535
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201216-100504535
Official Citation:Chang CC, Chu A, Meyer S, Ding Y, Sun MM, Abiri P, Baek KI, Gudapati V, Ding X, Guihard P, Bostrom KI, Li S, Gordon LK, Zheng JJ, Hsiai TK. Three-dimensional Imaging Coupled with Topological Quantification Uncovers Retinal Vascular Plexuses Undergoing Obliteration. Theranostics 2021; 11(3):1162-1175. doi:10.7150/thno.53073
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107116
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:16 Dec 2020 18:36
Last Modified:16 Dec 2020 18:36

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