Development of a mouse model to study microglia function during diabetic retinopathy

Diabetic retinopathy (DR) is the leading cause of blindness in working Americans and is observed as a common complication of diabetes mellitus. It is believed that visual dysfunction develops due to vascular dysfunction and neuronal degeneration. Resident microglia cells can play detrimental and protective roles during CNS inflammation, but the regulation of their effector functions remains unclear. Previous data from our laboratory showed that in the normal CNS the fractalkine receptor (CX3CR1) inhibits microglia activation and neurotoxicity. Microglia within the retina were activated as diabetes developed leading to inflammation response, hence we sought to investigate the role of CX3CR1 on retinal microglia in DR.

In this study, we use the diabetic animal model Ins2 Akt, to examine microglia activation and neuronal damage in eye tissues by image analysis and identifying inflammation-related factors by PCR array. Our preliminary data shows a decrease number of retinal ganglion cells in the retina of diabetic mice with peripheral CX3CR1 deficiency. In contrary, a decreased number of dopaminergic amacrine cells were observed in the retina of diabetic mice with normal function of CX3CR1. These data indicate that CX3CR1 plays an important role in neurodegeneration during DR.