July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Arterial and Venous Density during Early NPDR by Fractal Dimension: Association with Loss of Protective RAS
Author Affiliations & Notes
  • Patricia A Parsons-Wingerter
    NASA, Moffett Field, California, United States
  • Krishnan Radhakrishnan
    U.S. Department of Veterans Affairs, Clinical Epidemiology Research Center, West Haven, Connecticut, United States
    Department of Internal Medicine, College of Medicine University of Kentucky, Lexington, Kentucky, United States
  • Matthew C. Murray
    NASA, Moffett Field, California, United States
    Blue Marble Space Institute of Science (BMSIS), Moffett Field, California, United States
  • Sneha Ramesh
    NASA, Moffett Field, California, United States
    Blue Marble Space Institute of Science (BMSIS), Moffett Field, California, United States
  • Hamed Valizadegan
    NASA, Moffett Field, California, United States
    Universities Space Research Association (USRA), Mountain View, California, United States
  • Elaine Ma
    Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
  • Srinivaas Sekaran
    Georgia Institute of Technology, Atlanta, Georgia, United States
  • Yaqian Duan
    Indiana University School of Medicine, Indianapolis, Indiana, United States
    Department of Integrative and Cellular Physiology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • K V Chalam
    Department of Ophthalmology, University of Florida, Jacksonville, Florida, United States
  • Maria Grant
    Department of Ophthalmology, University of Alabama, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Patricia Parsons-Wingerter, None; Krishnan Radhakrishnan, None; Matthew Murray, None; Sneha Ramesh, None; Hamed Valizadegan, None; Elaine Ma, None; Srinivaas Sekaran, None; Yaqian Duan, None; K V Chalam, None; Maria Grant, None
  • Footnotes
    Support  NHLBI R01HL110170, NASA Center Innovation Fund 2017
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3548. doi:
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      Patricia A Parsons-Wingerter, Krishnan Radhakrishnan, Matthew C. Murray, Sneha Ramesh, Hamed Valizadegan, Elaine Ma, Srinivaas Sekaran, Yaqian Duan, K V Chalam, Maria Grant; Arterial and Venous Density during Early NPDR by Fractal Dimension: Association with Loss of Protective RAS. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3548.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Vascular damage and altered repair are implicated in the pathogenesis of diabetic retinopathy (DR). The renin-angiotensin system (RAS) has been associated with accelerated vascular damage and altered repair, and specifically with the dysfunction of circulating angiogenic cells (CACs), a critical bone marrow-derived population involved in vascular remodeling. For this prospective study, we are testing the hypothesis that retinal vascular density increases during early-stage nonproliferative DR (NPDR), based on previous results from a small retrospective study (IOVS 51(1):498).

Methods : Vascular patterns were extracted from Heidelberg Spectralis® FA-OCT images of 13 control, 7 mild NPDR and 5 moderate NPDR retinas as a significant study expansion beyond the ARVO 2016 report. Automated unsupervised (image segmentation) and supervised (e.g., deep learning) machine learning methods are replacing previous semi-automated vessel extraction. Vascular branching was mapped and quantified by NASA’s VESsel GENeration Analysis (VESGEN) software that includes calculation of the fractal dimension (Df) from skeletonized vascular images by the box-counting method. Df, a sensitive measure of vascular space-filling pattern, varies between the limiting Euclidean dimensions of 1 and 2. For this NPDR cohort, we assessed changes in the migratory function of CACs and gene expression of Mas, the receptor for Ang-(1-7) and a key component of vascular-protective RAS, to determine whether changes were associated with retinal vascular remodeling.

Results : By Df (mean ± SD), venous and arterial densities were 1.37 ± 0.02 and 1.32 ± 0.03 for mild NPDR, and 1.37 ± 0.02 and 1.33 ± 0.03 for moderate NPDR, compared to 1.32 ± 0.02 and 1.31 ± 0.03 for controls. A significant increase in veins and lesser increase in arteries during early NPDR is demonstrated. Migratory dysfunction of CACs correlated with severity of DR. Compared to controls, Mas receptor mRNA in CACs of diabetics without DR was increased. However, levels were reduced with NPDR onset, indicating possible loss of compensation of protective RAS in early DR.

Conclusions : As assessed by the fractal dimension, the space-filling capacity of both veins and arteries was greater in early NPDR than in controls. Results suggest that loss of the protective RAS axis within diabetic CACs is associated with increased vascular damage and remodeling during DR.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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