title: Long-term, topical insulin administration increases the severity of retinal vascular pathology in streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  We previously reported that insulin accumulated in the retina of diabetic rats after topical insulin eye drop treatment. In light of insulin's reported benefits to the retina, we hypothesized that the delivery of insulin to the retina by eye drop application might be efficacious in preventing diabetic retinopathy.
  
  
  METHODS
  We applied daily, uni-ocular porcine insulin drops (0.75%) to diabetic rats for 14 months and then analyzed their retinas for vascular pathology.
  
  
  RESULTS
  Our data showed that high-dose insulin eye drop treatment increased the number of retinal acellular capillaries, with many of these capillaries exhibiting a degenerated, threadlike appearance. The retinas also showed extensive capillary obliteration and had tangled masses of vascular cells. The glycated hemoglobin levels of eye drop-treated rats were similar to those found in control, vehicle-treated diabetic animals at sacrifice. Retinal insulin levels remained elevated after a 2-week regimen of daily insulin eye drops, suggesting that our treatment protocol resulted in the pooling of insulin in the retina. A similar treatment regimen was also found to have no effect on retinal glucose concentration.
  
  
  CONCLUSIONS
  Our results showed that treatment of diabetic rats with daily, high-dose insulin eye drops intensified their retinal pathology.
authors.affiliation: Department of Biomedical Sciences and Disease, New England College of Optometry, Boston, Massachusetts 02115, USA. koevary@neco.edu
authors.forename: Steven B
authors.initials: SB
authors.lastname: Koevary
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nussey
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index
chemical_list: D007328:Insulin