July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Neurovascular coupling impariment and vasomotor decline in a murine model of diabetic retinopathy
Author Affiliations & Notes
  • Botir T. Sagdullaev
    Burke Neurological Institute, Weill Cornell Medicine, White Plains, New York, United States
  • Tamas Kovacs-Oller
    Burke Neurological Institute, Weill Cornell Medicine, White Plains, New York, United States
  • Elena Ivanova
    Burke Neurological Institute, Weill Cornell Medicine, White Plains, New York, United States
  • Footnotes
    Commercial Relationships   Botir Sagdullaev, None; Tamas Kovacs-Oller, None; Elena Ivanova, None
  • Footnotes
    Support  R01-EY026576
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 983. doi:
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    • Get Citation

      Botir T. Sagdullaev, Tamas Kovacs-Oller, Elena Ivanova; Neurovascular coupling impariment and vasomotor decline in a murine model of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):983.

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

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Abstract

Purpose : From its onset, diabetic retinopathy is characterized by inability of blood supply to match neuronal activity. These interactions occur at the level of capillaries, where pericytes, the only contractile cells, adjust the capillary diameter in response to neuronal signals. Here, we determine the mechanisms that contribute to neurovascular coupling impariment and vasomotor decline in diabetic retinopathy.

Methods : In NG2-DsRed mice pericytes were distinguished from other mural cells using live NT500 assay. Surrounding neurovascular and glial cells were distingushed using immunohistochemistry. Direct cell-to-cell communications were determined using electrophoretic infusion of gap-junction-permeable Neurobiotin tracer. Vasomotor response was assessed in wholemount retina to a focal single pericyte stimulation via patch pippette. Changes in cellular function were assessed using NG2-GCaMP6f mice, in which Ca indicator is genetically expressed in the majority of retinal cells. All statistical analyses were perfomed using t-test or, for multiple comparisons, ANOVA with post-hoc correction.

Results : We found that pericytes form a precise 3-D mosaic across retinal vascular layers. To test if this symmetric organization of the vasomotor elements predicted a connectivity map in response to sensory stimulation, we utilized a cell-to-cell tracing approach. Surprisingly, we found that the connections among pericytes and other neurovascular elements were highly asymmetric spatially, and discriminatory across the cell types. In particular, pericytes formed direct gap-junction-mediated connections exclusively with other pericytes and endothelial cells, but neither to arteriolar smooth muscle cells nor to neurons and glia. Focal light stimulation promoted these connectivity maps by strengthening pericyte and endothelial cell coupling, Ca-signaling and vasomotor response along a vascular branch feeding the active site. STZ-treatment, leading to diabetic retinopathy, reduced significantly the cellular coupling and weakened the directionality of the vasomotor response towards the supplying branch.

Conclusions : Our findings reveal that neurovascular interactions are more nuanced and discriminatory across distinct cells than have been previously thought, providing a novel view on their dynamic role in normal function and pathophysiology.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Connectome of a pericyte and other neurovascular elements in the living retina.

Connectome of a pericyte and other neurovascular elements in the living retina.

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