Abstract
Purpose :
In diabetic retinopathy (DR), cell-cell coupling appears to be compromised, leading to retinal vascular cell death and the development of retinal vascular lesions. The aim of this study is to evaluate whether administration of a gap junction coupler may be protective against retinal vascular cell death in the retinas of diabetic rats.
Methods :
To determine the optimal concentration of danegaptide (DG), a Cx43 gap junction coupler, two concentrations (200 nM or 1000 nM) were tested via intravitreal injections in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced via STZ for 6 weeks and at the end of the study, eyes were enucleated, and retinas subjected to retinal trypsin digest (RTD) for isolation of capillary networks and stained with Hematoxylin and Periodic Acid Schiff (PAS) to analyze the number of acellular capillaries (AC) and pericyte loss (PL). Based on this pilot study, 1000 nM DG was found to be optimal and therefore injected intravitreally in the follow-up study to determine the effects of improved cell coupling on retinal vascular cell death. Additionally, DG was administered systemically via osmotic pumps. The number of rats used in this study was at least 6 per group. Overall, rats were divided into 6 groups: wild type (WT) control rats, STZ-induced diabetic rats, diabetic rats intravitreally injected with DG, diabetic rats intravitreally injected with water, diabetic rats systemically delivered with DG, and diabetic rats systemically delivered with water. Diabetes was induced for 15 weeks and at the end of the study all animals were sacrificed and their retinas were isolated and subjected to RTD for analyses of AC and PL.
Results :
The retinal vasculature showed a significant decrease in the development of AC in diabetic rats treated either via intravitreal injections or systemically with DG (134±28% of control, p<0.01 and 133±37% of control, p<0.001, respectively) compared to those of diabetic rats (296±26% of control, p<0.001). Likewise, retinal capillaries of diabetic rats treated intravitreally or systemically with DG exhibited a significant decrease in the number of PL (112±62% of control, p<0.01 and 103±65% of control, p<0.005, respectively) compared to those of diabetic rats (335±40%, p<0.005).
Conclusions :
Findings from this study indicate that improved cell-cell coupling may be protective against retinal vascular cell death associated with DR.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.