title: Theoretical analysis of vascular regulatory mechanisms contributing to retinal blood flow autoregulation.
abstract: OBJECTIVE
  To study whether impaired retinal autoregulation is a risk factor for glaucoma, the relationship between vascular regulatory mechanisms and glaucoma progression needs to be investigated. In this study, a vascular wall mechanics model is used to predict the relative importance of regulatory mechanisms in achieving retinal autoregulation.
  
  
  METHODS
  Resistance vessels are assumed to respond to changes in pressure, shear stress, carbon dioxide (CO2), and the downstream metabolic state communicated via conducted responses. Model parameters governing wall tension are fit to pressure and diameter data from porcine retinal arterioles. The autoregulation pressure range for control and elevated levels of IOP is predicted.
  
  
  RESULTS
  The factor by which flow changes as the blood pressure exiting the central retinal artery is varied between 28 and 40 mm Hg is used to indicate the degree of autoregulation (1 indicates perfect autoregulation). In the presence of only the myogenic response mechanism, the factor is 2.06. In the presence of the myogenic and CO2 responses, the factor is 1.22. The combination of myogenic, shear, CO2, and metabolic responses yields the best autoregulation (factor of 1.10).
  
  
  CONCLUSIONS
  Model results are compared with flow and pressure data from multiple patient studies, and the combined effects of the metabolic and CO2 responses are predicted to be critical for achieving retinal autoregulation. When IOP is elevated, the model predicts a decrease in the autoregulation range toward low perfusion pressure, which is consistent with observations that glaucoma is associated with decreased perfusion pressure.
authors.affiliation: Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202, USA. jarciero@math.iupui.edu
authors.forename: Julia
authors.initials: J
authors.lastname: Arciero
authors.forename: Alon
authors.initials: A
authors.lastname: Harris
authors.forename: Brent
authors.initials: B
authors.lastname: Siesky
authors.forename: Annahita
authors.initials: A
authors.lastname: Amireskandari
authors.forename: Victoria
authors.initials: V
authors.lastname: Gershuny
authors.forename: Aaron
authors.initials: A
authors.lastname: Pickrell
authors.forename: Giovanna
authors.initials: G
authors.lastname: Guidoboni
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology; D001783:Blood Flow Velocity / Q000502:physiology; D005901:Glaucoma / Q000503:physiopathology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D008955:Models, Cardiovascular; D012039:Regional Blood Flow / Q000502:physiology; D012171:Retinal Vessels / Q000502:physiology*; D013552:Swine; D014655:Vascular Resistance / Q000502:physiology*; D014699:Venules / Q000502:physiology
keywords: autoregulation; blood flow regulation; glaucoma; metabolic response; myogenic response; retina