title: Progressive Early Breakdown of Retinal Pigment Epithelium Function in Hyperglycemic Rats.
abstract: Diabetic macular edema (DME), an accumulation of fluid in the subretinal space, is a significant cause of vision loss. The impact of diabetes on the breakdown of the inner blood-retina barrier (BRB) is an established event that leads to DME. However, the role of the outer BRB in ocular diabetes has received limited attention. We present evidence that the breakdown of normal RPE function in hyperglycemia facilitates conditions conducive to DME pathogenesis.
  
  
  
  Brown Norway rats (130-150 g) were injected intraperitoneally with streptozotocin (STZ; 60 mg/kg) to induce hyperglycemia. After 4 weeks, Evans blue (EB) dye was injected intravenously to determine whether there was leakage of albumin into the retina. Subretinal saline blebs (0.5-1 μL) were placed 4 and 9 weeks after STZ injection, and time-lapse optical coherence tomography tracked the resorption rate. In a subset of rats, intravitreal bevacizumab, a humanized monoclonal antibody targeted to VEGF, was given at 5 weeks and resorption was measured at 9 weeks.
  
  
  
  The ability of the RPE to transport fluid was reduced significantly after 4 and 9 weeks of hyperglycemia with a reduction of over 67% at 9 weeks. No EB dye leakage from inner retinal vessels was measured in hyperglycemic animals compared to control. The intravitreal administration of bevacizumab at week 5 significantly increased the rate of fluid transport in rats subjected to hyperglycemia for 9 weeks.
  
  
  
  These results demonstrate that chronic hyperglycemia altered RPE fluid transport, in part dependent on the actions of VEGF. These results support the idea that RPE dysfunction is an early event associated with hyperglycemia that contributes to fluid accumulation in DME.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Desjardins
authors.forename: Phil W
authors.initials: PW
authors.lastname: Yates
authors.forename: Mohammad
authors.initials: M
authors.lastname: Dahrouj
authors.forename: Yueying
authors.initials: Y
authors.lastname: Liu
authors.forename: Craig E
authors.initials: CE
authors.lastname: Crosson
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ablonczy
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage; D001813:Blood-Retinal Barrier / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006943:Hyperglycemia / Q000150:complications* / Q000175:diagnosis; D015151:Immunoblotting; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab