Figure 10.

Proposed novel signaling pathway in the development of diabetic retinopathy. During diabetes, leaked glycated proteins initiate the inflammatory cascade of DR through activation of ADA2 in macrophages and production of soluble inflammatory cytokines like TNF-α and IL-6, which activate leukocyte adhesion to retinal endothelial cells and finally leads to disruption of tight junction proteins and breakdown of the BRB. MicroRNA-146b-3p might be able to inhibit the production of inflammatory cytokines from macrophages through inhibition of ADA2 and subsequently might protect BRB. This signaling pathway suggests ADA2 as a potential therapeutic target to prevent or at least minimize the microvascular dysfunction in DR.