Detection of microvascular retinal changes in type I diabetic mice with optical coherence tomography angiography

Hironori Uehara, Timilai Lesuma, Parker Stocking, Nathan Jensen, Sangeetha Ravi Kumar, Mingyang Aaron Zhang, Susie Choi, Xiaohui Zhang, Bonnie Archer, Lara Carroll, Balamurali Krishna Ambati

Research output: Contribution to journalArticle

Abstract

Optical coherence tomography (OCT) angiography is a dye-free and non-invasive angiography which allows visualization of retinal and choroid vascular flow, enabling observation of highly permeable and three dimensional vasculature. Although OCT angiography is providing new insights in human retinal and choroidal diseases, a few studies have been reported in experimental mice. In this study, to determine the potential of OCT angiography in experimental mice, we sought to examine whether OCT angiography can detect vascular change in type I diabetic mice. To conduct age dependent analysis, 2 and 6 month old male type 1 diabetic Ins2Akita/+ and age matched C57BL/6J mice were used. OCT angiography was performed by Heidelberg Spectralis OCT Angiography Module with 30° lens + mouse adapter lens. We acquired the OCT angiography image from the peripheral nasal position. For analysis of OCT angiography images, OCT angiography positive area were used for vascular density. We analyzed vascular density from the retinal surface (inner limiting membrane) to 120 μm depth with 4 μm steps in order to correlate vascular density vs depth (N = 4 per group). Vascular density of both mouse strains demonstrated three different peaks. By comparing with the OCT image, the first peak (superficial), second peak (intermediate) and third peak (deep) were located in nerve fiber layer/ganglion cell layer, inner plexiform layer/inner nuclear layer and outer plexiform layer/outer nuclear layer, respectively. We calculated vascular density of these peaks separately. In C57BL/6J mice, the vascular density in all three layers do not show significant difference between 2- and 6-month-old. On the other hand, 6-month-old Ins2Akita/+ mice showed a significant decrease of the vascular density in all three layers compared to 2-month-old Ins2Akita/+ mice. Also, the vascular density of 6-month-old Ins2Akita/+ mice in the deep layer showed a significant decrease compared to 2- and 6-month-old C57BL/6J mice. Thus, OCT angiography successfully detects retinal vascular difference between type I diabetic mice and control mice, and age-dependent vasculature change in type I diabetic mice. The diabetic mice demonstrated reduced vascular density due to reduced density of flowing deep vessels. Importantly, we observed this difference without retinal blood leakage, hemorrhage or neovascularization. Our analysis (vascular density vs retinal depth) suggests that OCT angiography is useful for in vivo detection of retinal vasculature alteration in experimental mice.

LanguageEnglish (US)
Pages91-98
Number of pages8
JournalExperimental Eye Research
Volume178
DOIs
StatePublished - Jan 1 2019

Fingerprint

Optical Coherence Tomography
Angiography
Blood Vessels
Inbred C57BL Mouse
Retinal Vessels
Lenses
Choroid Diseases
Retinal Diseases
Choroid
Nerve Fibers
Nose
Ganglia
Coloring Agents
Observation

Keywords

  • Murine diabetic retinopathy
  • Optical coherence tomography angiography

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Detection of microvascular retinal changes in type I diabetic mice with optical coherence tomography angiography. / Uehara, Hironori; Lesuma, Timilai; Stocking, Parker; Jensen, Nathan; Kumar, Sangeetha Ravi; Zhang, Mingyang Aaron; Choi, Susie; Zhang, Xiaohui; Archer, Bonnie; Carroll, Lara; Ambati, Balamurali Krishna.

In: Experimental Eye Research, Vol. 178, 01.01.2019, p. 91-98.

Research output: Contribution to journalArticle

Uehara, H, Lesuma, T, Stocking, P, Jensen, N, Kumar, SR, Zhang, MA, Choi, S, Zhang, X, Archer, B, Carroll, L & Ambati, BK 2019, 'Detection of microvascular retinal changes in type I diabetic mice with optical coherence tomography angiography' Experimental Eye Research, vol. 178, pp. 91-98. https://doi.org/10.1016/j.exer.2018.09.017
Uehara, Hironori ; Lesuma, Timilai ; Stocking, Parker ; Jensen, Nathan ; Kumar, Sangeetha Ravi ; Zhang, Mingyang Aaron ; Choi, Susie ; Zhang, Xiaohui ; Archer, Bonnie ; Carroll, Lara ; Ambati, Balamurali Krishna. / Detection of microvascular retinal changes in type I diabetic mice with optical coherence tomography angiography. In: Experimental Eye Research. 2019 ; Vol. 178. pp. 91-98.
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