Diabetic retinopathy (DR) is one of the most common complications of diabetes and major cause of
blindness among people over 50 years old. Current studies showed that the
vascular endothelial growth factor (
VEGF) played a central role in the pathogenesis of DR, and application of anti-
VEGF has been widely acknowledged in treatment of DR targeting
retinal neovascularization. However, anti-
VEGF therapy has several limitations such as drug resistance. It is essential to develop new drugs for future clinical practice. The vitreous takes up 80% of the whole globe volume and is in direct contact with the retina, making it possible to explore the pathogenesis of DR by studying related factors in the vitreous. This article reviewed recent studies on DR-related factors in the vitreous, elaborating the
VEGF upstream
hypoxia-inducible factor (HIF) pathway and downstream pathways
phosphatidylinositol diphosphate (PIP2), phosphoinositide-3-kinase (PI3K), and
mitogen-activated protein kinase (MAPK) pathways. Moreover, factors other than
VEGF contributing to the pathogenesis of DR in the vitreous were also summarized, which included factors in four major systems, kallikrein-kinin system such as
bradykinin,
plasma kallikrein, and
coagulation factor XII, oxidative stress system such as
lipid peroxide, and
superoxide dismutase,
inflammation-related factors such as
interleukin-1β/6/13/37, and
interferon-γ,
matrix metalloproteinase (
MMP) system such as
MMP-9/14. Additionally, we also introduced other DR-related factors such as
adiponectin, certain specific
amino acids,
non-coding RNA and
renin (pro) receptor in separate studies.