Abstract
Diabetic retinopathy is a vascular disease of the retina characterised by hyperglycaemic and inflammatory processes. Most animal models of diabetic retinopathy are hyperglycaemia-only models that do not account for the significant role that inflammation plays in the development of the disease. In the present study, we present data on the establishment of a new animal model of diabetic retinopathy that incorporates both hyperglycaemia and inflammation. We hypothesized that inflammation may trigger and worsen the development of diabetic retinopathy in a hyperglycaemic environment. Pro-inflammatory cytokines, IL-1β and TNF-α, were therefore injected into the vitreous of non-obese diabetic (NOD) mice. CD1 mice were used as same genetic background controls. Fundus and optical coherence tomography images were obtained before (day 0) as well as on days 2 and 7 after intravitreal cytokine injection to assess vessel dilation and beading, retinal and vitreous hyper-reflective foci and retinal thickness. Astrogliosis and microgliosis were assessed using immunohistochemistry. Results showed that intravitreal cytokines induced vessel dilation, beading, severe vitreous hyper-reflective foci, retinal oedema, increased astrogliosis and microglia upregulation in diabetic NOD mice. Intravitreal injection of inflammatory cytokines into the eyes of diabetic mice therefore appears to provide a new model of diabetic retinopathy that could be used for the study of disease progression and treatment strategies.
Highlights
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes leading to vascular breakdown in the retina
It is important to note that the blood glucose levels in non-obese diabetic (NOD) mice was likely an underestimate as readings above 27.8 mmol/L were taken as 27.8 mmol/L
The additional signs observed in NOD mice included vessel beading, more severe vitreous hyper-reflective foci (HRF), retinal HRF, sub-retinal fluid accumulation, increased nerve fibre layer (NFL)-ganglion cell layer (GCL)-inner plexiform layer (IPL) thickness, and more severe retinal and optic nerve astrogliosis and microgliosis (Table 2)
Summary
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes leading to vascular breakdown in the retina. In 2014, approximately 370 million people suffered from diabetes worldwide [1]. This number is expected to double by 2030 meaning that 1 in 5 adults will suffer from the disease. DR is primarily a vascular disease characterised by endothelial cell [2] and pericyte loss [3] as well as blood retinal barrier (BRB) breakdown [4,5].
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