title: Defective Myogenic Response of Retinal Vessels Is Associated With Accelerated Onset of Retinopathy in Type 1 Diabetic Individuals.
abstract: OBJECTIVE
  We seek to identify pathogenic mechanisms for diabetic retinopathy that can become therapeutic targets beyond hyperglycemia and hypertension. We investigated if a defective myogenic response of retinal arteries to increased perfusion pressure, which exposes capillaries to increased pressure and flow, is associated with the onset of clinical retinopathy.
  
  
  METHODS
  We examined prospectively the incidence of retinopathy in type 1 diabetic individuals tested 4 years earlier for the retinal arterial myogenic response, and in a cross-sectional study the prevalence of defective myogenic response in type 1 patients who had diabetic retinopathy. Among these, we contrasted early-onset (after 15 ± 2 years of diabetes, E-DR; n = 5) to late-onset (after 26 ± 3 years of diabetes, L-DR; n = 7) retinopathy. We measured the myogenic response using a laser Doppler blood flowmeter after a change in posture from sitting to reclining, which increases retinal perfusion pressure.
  
  
  RESULTS
  Five of seven participants who 4 years prior had a defective myogenic response had now developed clinical retinopathy; as compared with only one of six participants who 4 years prior had a normal response (P = 0.10). In the cross-sectional study, all participants had normal retinal hemodynamics at steady state. In response to the postural change, only the E-DR group showed defective myogenic response (P = 0.005 versus controls, P = 0.02 versus L-DR) and abnormally high retinal blood flow (P = 0.016 versus controls).
  
  
  CONCLUSIONS
  In type 1 diabetic patients, a defective myogenic response of retinal arteries to pressure is not required for the development of clinical retinopathy, but is prominently associated with an accelerated onset of retinopathy.
authors.affiliation: Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tecilazich
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Gilbert T
authors.initials: GT
authors.lastname: Feke
authors.affiliation: Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Sara
authors.initials: S
authors.lastname: Mazzantini
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Lucia
authors.initials: L
authors.lastname: Sobrin
authors.affiliation: Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Mara
authors.initials: M
authors.lastname: Lorenzi
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001794:Blood Pressure; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D010477:Perfusion; D011446:Prospective Studies; D012039:Regional Blood Flow; D012161:Retinal Artery / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human