Abstract
Vascular dysfunction and vasoregression are hallmarks of a variety of inflammatory central nervous system disorders and inflammation-related retinal diseases like diabetic retinopathy. Activation of microglia and the humoral innate immune system are contributing factors. Anti-inflammatory approaches have been proposed as therapies for neurovascular diseases, which include the modulation of microglial activation. The present study aimed at investigating the effects of microglial activation by clodronate-coated liposomes on vasoregression in a model of retinal degeneration. Clodronate treatment over 5 weeks led to an increase in activated CD74+ microglia and completely prevented acellular capillaries and pericyte loss. Gene expression analyses indicated that vasoprotection was due to the induction of vasoprotective factors such as Egr1, Stat3, and Ahr while expression of pro-inflammatory genes remained unchanged. We concluded that activated microglia led to a shift toward induction of pleiotropic protective pathways supporting vasoprotection in neurovascular retinal diseases.
Highlights
The evolution of neurodegeneration and vascular dysfunction is a hallmark of a variety of central nervous disorders including Alzheimer’s disease, stroke, and retinal diseases like diabetic retinopathy (Marques et al, 2013; Prakash et al, 2013; Hammes, 2018; Jiang et al, 2018)
We demonstrate vasoprotective effects associated with clodronate-coated liposome-induced microglial activation
Vasoprotection was accompanied by the induction of Ahrdependent protective factors in the course of microglial activation, which are possible effectors mediating the vasoprotective effects
Summary
The evolution of neurodegeneration and vascular dysfunction is a hallmark of a variety of central nervous disorders including Alzheimer’s disease, stroke, and retinal diseases like diabetic retinopathy (Marques et al, 2013; Prakash et al, 2013; Hammes, 2018; Jiang et al, 2018). It is proposed that microglia, activated by degenerating neurons, communicate inflammation into the neurovascular unit and cause vascular dysfunction and vasoregression (Kisler et al, 2017a). As the retina and the brain are similar in the structure of the neurovascular unit, the eye can be used as a biomarker for pathogenic processes in the central nervous system (Lim et al, 2016).
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