Background: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the main cause of non-traumatic blindness in adults. Pericyte loss is known to be an early pathological change of DR. Our group's previous research indicated that prostaglandin F2α (PGF2α) acts as an eicosanoidal protector against non-proliferative DR that can regulate the mobility of pericytes in a RhoA-mediated manner. However, the effect of PGF2α on pericyte apoptosis has yet to be described.
Methods: Two animal models were constructed: a high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes mouse model and a spontaneous type 2 diabetes db/db mouse model. We analyzed pathological changes, and performed TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining and western blot to detect apoptosis in the retinas of diabetic mice. For our in vitro experiments, we selected human retinal pericytes and subjected them to high-glucose (HG), PGF2α, and AL8810 (an antagonist of the PGF2α receptor) treatment. Subsequently, apoptosis and the levels of PI3K/Akt/GSK3β/β-catenin pathway-related proteins were detected by TUNEL staining and western blot, respectively.
Results: The levels of apoptosis were increased in the retinas of diabetic mice in both T2DM models. In vitro, HG treatment increased apoptosis and inhibited PI3K/Akt/GSK3β/β-catenin signaling in pericytes. In contrast, PGF2α treatment inhibited pericyte apoptosis while increasing the levels of the PI3K, p-Akt/t-Akt, p-GSK3β/t-GSK3β, and β-catenin proteins; however, these PGF2α-induced effects were eliminated by ALL80.
Conclusions: PGF2α may make a key contribution to reducing pericyte apoptosis and protecting against DR via its inhibition of the PI3K/Akt/GSK3β/β-catenin signaling pathway.
Keywords: Diabetic retinopathy (DR); apoptosis; pericytes; prostaglandin F2α (PGF2α).
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