September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy
Author Affiliations & Notes
  • Yaqian Duan
    Ophthalmology, IUPUI, Indianapolis, Indiana, United States
    Integrative and Cellular Physiology, IUPUI, Indianapolis, Indiana, United States
  • Rehae C Miller
    Ophthalmology, IUPUI, Indianapolis, Indiana, United States
  • Leni Moldovan
    Ophthalmology, IUPUI, Indianapolis, Indiana, United States
  • Eleni Beli
    Ophthalmology, IUPUI, Indianapolis, Indiana, United States
  • Tatiana Salazar
    Ophthalmology, IUPUI, Indianapolis, Indiana, United States
  • Sugata Hazra
    Internal Medicine, University of Utah, Salt Lake City, Utah, United States
  • KV Chalam
    Ophthalmology, University of Florida, Jacksonville, Florida, United States
  • Sneha Raghunandan
    Space Life Sciences Research Branch, NASA Ames Research Center, Moffett Field, California, United States
  • Ruchi J Vyas
    Space Life Sciences Research Branch, NASA Ames Research Center, Moffett Field, California, United States
  • Patricia A Parsons-Wingerter
    Space Life Sciences Research Branch, NASA Ames Research Center, Moffett Field, California, United States
  • Maria B Grant
    Ophthalmology, IUPUI, Indianapolis, Indiana, United States
  • Footnotes
    Commercial Relationships   Yaqian Duan, None; Rehae Miller, None; Leni Moldovan, None; Eleni Beli, None; Tatiana Salazar, None; Sugata Hazra, None; KV Chalam, None; Sneha Raghunandan, None; Ruchi Vyas, None; Patricia Parsons-Wingerter, None; Maria Grant, None
  • Footnotes
    Support  NIH grants: R01EY0126001, R01EY007739, R01HL110170, R01DK090730. Research to Prevent Blindness Unrestricted grant awarded to the Department of Ophthalmology at IUPUI.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2721. doi:
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      Yaqian Duan, Rehae C Miller, Leni Moldovan, Eleni Beli, Tatiana Salazar, Sugata Hazra, KV Chalam, Sneha Raghunandan, Ruchi J Vyas, Patricia A Parsons-Wingerter, Maria B Grant; Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2721.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : In diabetes, the impaired vasoreparative function of circulating angiogenic cells (CACs) is believed to contribute to the progression of diabetic retinopathy (DR). Accumulating evidence suggests that the protective arm of renin-angiotensin system (RAS) “ACE2/Angiotensin-(1-7)/Mas” plays an important role in restoring the function of diabetic CACs. We examined the protective RAS in CACs in diabetic individuals with different stages of retinopathy.

Methods : Study subjects (n=43) were recruited as controls or diabetics with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fundus photography and fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects (n=5). CD34+ CACs were isolated from peripheral blood of diabetics and control subjects. RAS gene expressions in CACs were measured by qPCR. The vasoreparative function of CACs was assessed by migration ability toward CXCL12 using the QCM 5μM 96-well chemotaxis cell migration assay.

Results : ACE2 gene is a key enzyme converting the deleterious Angiotensin II to the beneficial Angiotensin-(1-7). ACE2 expression in CACs from diabetic subjects without DR was increased compared to controls, suggestive of compensation (p=0.0437). The expression of Mas (Angiotensin-(1-7) receptor) in CACs was also increased in diabetics without DR, while was reduced in NPDR compared to controls (p=0.0002), indicating a possible loss of compensation of the protective RAS at this stage of DR. The presence of even mild NPDR was associated with CD34+ CAC migratory dysfunction. When pretreating CACs of DR subjects with Angiotensin-(1-7), migratory ability to a chemoattractant CXCL12 was restored (p=0.0008). By VESGEN analysis, an increase in small vessel density was observed in NPDR subjects when compared with the controls.

Conclusions : These data suggest the protective RAS axis within diabetic CACs may help maintain their vasoreparative potential. The VESGEN analysis supports the presence of retinal repair in small vessels. The loss of the protective arm of RAS may predict the progression of DR.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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