Abstract
Purpose :
Abnormalities in retina circulations and its regulation occur in diabetes mellitus (DM). The measurement of retinal blood flow using fluorescein angiography (FA) provides a method to monitor the retinal circulation and its regulation in DM. This work investigated retinal blood flow changes in highly translatable models of diabetic and age matched normal non-human primates.
Methods :
KBI currently has over 3000 male cynomolguses with metabolic diseases caused by either high fat diet (HFD) feeding or natural aging. Metabolic disease was monitored longitudinally using body weight, intravenous glucose tolerance tests (ivGTT), blood pressure and clinical chemistry. DM were diagnosed based on following requirements: fasting glucose level > 100mg/dL, glucose disposal rate < 1.3% and hemoglobin A1c test (HbA1c) > 5%. Additionally, ivGTT results provided more guidelines for identifying diabetic cynomolgus monkeys.
For the assessment of retinal blood flow, all monkeys were anesthetized with IM ketamine (5-10 mg/kg) and xylazine (0.5-1 mg/kg). Fundus images in FA mode using a fundus camera with FA after a bolus iv injection of 0.2ml/kg, 10% sodium fluorescein (NaF). Retinal filling of artery starting time (AST), artery complete time (ACT), vein starting time (VST) and vein complete time (VCT) were recorded from FA photographs.
Results :
As a progress report, total of 155 monkeys have been studies, in which 107 monkeys were DM and others were age matched non-diabetes. In 73 DM monkeys with blood glucose > 100mg/dL or HbA1C > 5%, AST, ACT, VST and VCT were (in mean±se) 9.0±0.5, 11.0±0.6, 12±0.7 and 19±0.9 sec respectively. In contrast, in 82 age-matched normal monkeys with blood glucose ≤ 100 mg/dL and HbA1C ≤ 5%, AST, ACT, VST and VCT were 7±0.3, 9±0.4, 10±0.3 and 16±0.5 sec, respectively. AST, ACT, VST and VCT in DM monkeys were all significantly higher than those in normal monkeys (p<0.01).
Conclusions :
Retinal circulation in DM monkeys before the development of diabetic retinopathy is significantly slower than that in normal monkeys. These results indicated metabolic alterations in DM and their effects on the development of microvascular complications such as diabetic retinopathy.
This is a 2020 ARVO Annual Meeting abstract.