June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Increased levels of nitric oxide may pathologically affect functional hyperemia in the retina: model and simulation
Author Affiliations & Notes
  • Riccardo Sacco
    Mathematics, Politecnico di Milano, Italy, Milan, Italy
  • Aurelio Giancarlo Mauri
    Mathematics, Politecnico di Milano, Italy, Milan, Italy
  • Alessandra Cardani
    Mathematics, Politecnico di Milano, Italy, Milan, Italy
  • Brent A Siesky
    Ophthalmology, Indiana Univ Sch of Medicine, Indianapolis, Indiana, United States
  • Giovanna Guidoboni
    Mathematical Sciences, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Alon Harris
    Ophthalmology, Indiana Univ Sch of Medicine, Indianapolis, Indiana, United States
  • Footnotes
    Commercial Relationships   Riccardo Sacco, None; Aurelio Mauri, None; Alessandra Cardani, None; Brent Siesky, None; Giovanna Guidoboni, None; Alon Harris, AdOM (C), AdOM (I), Biolight (C), Isarna Therapeutics (C), Nano Retina (C), Nano Retina (I), Ono Pharmaceuticals (C), Oxymap (I), Science Based Health (C), Stemnion (C)
  • Footnotes
    Support  Statement of work #4505462139: "Modeling of tunneling and charging dynamics". Contractors: Micron Semiconductor Italia S.r.l.; Dipartimento di Matematica Politecnico di Milano, Italy
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 214. doi:
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    • Get Citation

      Riccardo Sacco, Aurelio Giancarlo Mauri, Alessandra Cardani, Brent A Siesky, Giovanna Guidoboni, Alon Harris; Increased levels of nitric oxide may pathologically affect functional hyperemia in the retina: model and simulation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):214.

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

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Abstract

Purpose : The role of nitric oxide (NO) in regulating neurovascular coupling (NVC) in the retina is still poorly understood. Experimental data of flicker light-induced functional hyperemia (FH) in humans (Newman et al (2013)) seem to indicate that increased NO levels mediated by 20- hydroxyeicosatetraeonic acid (20-HETE) reduce vasodilation. In this study we propose a multiphysics/multiscale mathematical model to theoretically investigate the effect of an increased level of neural NO (nNO) on the vasodilation of retinal arterioles.

Methods : Retinal vasculature is described by an equivalent electrical circuit (EEC) of resistive and capacitive compartments. NVC is described by the interaction between vasoactive agents synthesized by active neurons and astrocytes and smooth muscle cell contraction/dilation. Model inputs are blood pressure at the central retinal artery and vein, intraocular pressure, nNO and glutamate (GLU) post-synaptic levels. Kirchhoff current law is solved at each node of the circuit to determine the time evolution of nodal blood pressures and compartment diameters.

Results : Fig. 1 shows the simulated FH in humans for a GLU signal modeling a 20s flicker light stimulus. The y-axis is the % change in mean arterial diameter (MAD). Results indicate that FH is correctly represented only if both large and small arterioles (LA, SA) are assumed to be neurovascularly active (NVA). Fig. 2 shows the simulated effect on vasodilation due to a 60s stimulus of increased nNO level with respect to baseline (nNOb) added to GLU. Results indicate that elevated nNO may reduce vasodilation by a factor of 4.

Conclusions : Model simulations suggest that NVC has a noticeable impact on FH in the retina and that a value of nNO above baseline may significantly reduce vasodilation. These findings suggest that increased NO levels may be responsible for suppressing flicker-evoked vasodilation in diabetic retinopathy.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 


Fig. 1. Effect of NVA compartments on % change in MAD. Black circles: experimental data. Black line: simulation of a single LA. Blue line: simulation of EEC where only LAs are NVA. Red line: simulation of EEC where LAs and SAs are NVA.


Fig. 1. Effect of NVA compartments on % change in MAD. Black circles: experimental data. Black line: simulation of a single LA. Blue line: simulation of EEC where only LAs are NVA. Red line: simulation of EEC where LAs and SAs are NVA.

 


Fig. 2. Effect of nNO levels on % change in MAD. Black circles: experimental data. Red line: simulation of EEC with nNO = nNOb. Blue line: simulation of EEC with nNO > nNOb.


Fig. 2. Effect of nNO levels on % change in MAD. Black circles: experimental data. Red line: simulation of EEC with nNO = nNOb. Blue line: simulation of EEC with nNO > nNOb.

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