June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Spatial precision of the retinal blood supply and its impariment in early diabetic retinopathy
Author Affiliations & Notes
  • Botir T Sagdullaev
    Burke Neurological Institute, White Plains, New York, United States
    Ophthalmology, Weill Cornell Medicine, White Plains, New York, United States
  • Elena Ivanova
    Burke Neurological Institute, White Plains, New York, United States
  • Footnotes
    Commercial Relationships   Botir Sagdullaev, None; Elena Ivanova, None
  • Footnotes
    Support  NIH/NEI R01-EY026576 and R01-EY029796
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1774. doi:
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      Botir T Sagdullaev, Elena Ivanova; Spatial precision of the retinal blood supply and its impariment in early diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1774.

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

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Abstract

Purpose : Disrupted retinal capillary blood flow is an early sign of diabetic retinopathy. Here, we tested the hypothesis that the spatial accuracy of the blood supply to active retinal regions is driven by an exclusive and directional connectivity among pericytes and endothelial cells, and is imparied early in diabetes.

Methods : In control and STZ-treated male mice, we combined light simulation, direct cell-to-cell tracer coupling, multiphoton imaging of calcium activity, and the measurements of vasomotor response and blood flow

Results : We found that pericytes formed a precise 3-D mosaic across the retina with the conformity ratio (CR) significantly above randomly generated values, drawn from the same data set (4.47 ± 0.72 vs. 1.71 ± 0.19, P < 0.001, paired T-TEST, n = 48 ROIs in n = 16 mice). However, in response to visual stimulus, the vasomotor activity propagated asymmetrically towards the feeding branch. This directionality was driven along a highly discriminatory GJ-mediated vascular relay between pericytes and endothelial cells. We found that pericytes and endothelial cells connected predominantly to other upstream neighboring pericytes (coupling strength CS = 0.47 ± 0.11) and endothelial cells (CS = 0.51 ± 0.09, ), and less to arteriolar smooth muscles, and not to surrounding neurons and glia (CS < 0.10, n = 8 mice each). In diabetic mice (8-12 weeks after STZ injection) both coupling strength and the directionality of the vasomotor response were significantly reduced (CS = 0.12, DI = 0.7 vs 2.1 in non-diabetic control, n = 9 each) . Importantly, this was parallelled by a reduction of flicker-induced blood flow increase, a eally hallmark of diabetic retinopathy.

Conclusions : The changes to capillary blood flow precede anatomical and functional changes in diabetic retinopathy. This early onset establishes an opportunity window for prevention and treatment of more severe complications of the disease. In this work, we describe a functional map of pericytes and endothelial cells that mediate the spatial and temporal precision of neurovascular signaling in the retina. Our data establish mechanisms for regulation of vascular diameter along the vascular tree and how their disruption contribute to vascular blood flow impairment in early diabetes.

This is a 2020 ARVO Annual Meeting abstract.

 

Strength and directionality of pericyte coupling is driven by focal sensory input

Strength and directionality of pericyte coupling is driven by focal sensory input

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