Abstract
Purpose :
Proliferative diabetic retinopathy (PDR) and DME are the most common causes of severe vision loss in diabetic individuals. We evaluated various pro-angiogenic and pro-inflammatory biomarkers in the vitreous of subjects with PDR and DME. In this study, we evaluated whether these biomarkers are also altered in a double injection streptozotocin (STZ) model of diabetic retinal edema (DRE).
Methods :
Undiluted vitreous samples collected from non-diabetic controls (n=30), PDR without DME (n=35) and PDR with DME (n=30) were subjected to multiplexing, and a number of biomarkers were found to be significantly elevated in PDR/DME. These biomarkers were evaluated in Brown Norway rats (n= 5 per group) that were rendered diabetic using a double injection STZ protocol. Two injections of STZ or sham were given ten days apart, and animals were monitored for the development of diabetes. Rats were observed for 3.5 months and sacrificed. Plasma and eyes were collected from the rats, and subjected to RT-PCR and protein analyses.
Results :
In humans, there were no significant differences in age and gender among the PDR with DME, PDR without DME, and control groups. MANCOVA analysis of Controls vs. PDR/DME identified eight factors strongly associated with PDR/DME (P<0.05). These included PLGF, VEGF-A, TNF-α, Angiopoietin-2, IL-18, Leptin, Endoglin, and sCD40L. Twelve other factors were also identified via MANOVA, with significant P values (P<0.01). Diabetic rat specimens were probed for these factors using RT-PCR and protein analysis. A significant number of these factors showed similar changes in the double-injection rat diabetic model to those observed in the human condition.
Conclusions :
This study demonstrates that a variety of pro-angiogenic and pro-inflammatory markers are elevated in PDR and DME. The results show that the diabetic rat model mirrors the changes observed in the clinical condition. The double STZ injection Norwegian diabetic rat model mimics biomarker changes in DME. The model would be useful for identifying novel biomarkers for disease progression and detecting potential novel targets for intervention in the disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.