title: Changes in the density and localisation of endothelin receptors in the early stages of rat diabetic retinopathy and the effect of insulin treatment.
abstract: OBJECTIVE
  The endothelin system (ET system) has been implicated in the retinal blood flow abnormalities that precede the onset of diabetic retinopathy. This study was undertaken to assess whether the density and localisation of both the immunoreactive endothelin-1 and endothelin receptors in rat retina change in the early stages of diabetes and the insulin treatment would affect those changes.
  
  
  METHODS
  Untreated streptozotocin-diabetic, insulin-treated streptozotocin-diabetic and age-matched control rats were killed 15, 45 and 90 days after the induction of diabetes. Binding assays were used to determine the density and proportion of endothelin receptors in neural retinal membranes. Localisation of endothelin receptors and immunoreactive endothelin-1 were analysed by microautoradiography and immunohistochemistry, respectively.
  
  
  RESULTS
  Fifteen days after the induction of diabetes, the neural retinal membranes of untreated streptozotocin-diabetic rats showed a statistically significant decrease in the density of both endothelin receptor subtypes when compared with age-matched control rats. At 90 days, however, the density of endothelin receptors type B was statistically significantly higher than that of control rats, and the innermost layers of the diabetic retina also showed an increase of both endothelin receptor type B receptor and immunoreactive endothelin-1 signal. Insulin treatment during 90 days up-regulated endothelin receptor type A in neural retinal membranes and in the innermost layers of the retina when compared with control retinas.
  
  
  CONCLUSIONS
  These results show that the endothelin system is altered in both vascular and neuronal components of the retina in early diabetic retinopathy. The up-regulation of endothelin receptor type A induced by insulin treatment suggests that insulin might be involved in retinal microangiopathy.
authors.affiliation: Department of Internal Medicine III, Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: De Juan
authors.forename: F J
authors.initials: FJ
authors.lastname: Moya
authors.forename: A
authors.initials: A
authors.lastname: Ripodas
authors.forename: R
authors.initials: R
authors.lastname: Bernal
authors.forename: A
authors.initials: A
authors.lastname: Fernandez-Cruz
authors.forename: R
authors.initials: R
authors.lastname: Fernandez-Durango
mesh_terms: D000818:Animals; D001345:Autoradiography; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000503:physiopathology*; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D007457:Iodine Radioisotopes; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D019332:Endothelin-1; D007328:Insulin; D007457:Iodine Radioisotopes; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin