Repression of retinal microvascular endothelial cells by transthyretin under simulated diabetic retinopathy...

To investigate biological effects of transthyretin (TTR) on the development of neovascularization under simulated diabetic retinopathy (DR) condition associated with high glucose and hypoxia.

Human retinal microvascular endothelial cells (hRECs) were cultured in normal and simulated DR environments with high glucose and hypoxia. The normal serum glucose concentration is approximately 5.5 mmol/L; thus, hyperglycemia was simulated with 25 mmol/L glucose, while hypoxia was induced using 200 µmol/L CoCl2. The influence of TTR on hRECs and human retinal pigment epithelial cells (hRPECs) was determined by incubating the cells with 4 µmol/L TTR in normal and abnormal media. A co-culture system was then employed to evaluate the effects of hRPECs on hRECs.

Decreased hRECs and hRPECs were observed under abnormal conditions, including high-glucose and hypoxic media. In addition, hRECs were significantly inhibited by 4 µmol/L exogenous TTR during hyperglycemic culture. During co-culture, hRPECs inhibited hRECs in both the normal and abnormal environments.

hREC growth is inhibited by exogenous TTR under simulated DR environments with high-glucose and hypoxic, particularly in the medium containing 25 mmol/L glucose. hRPECs, which manufacture TTR in the eye, also represses hRECs in the same environment. TTR is predicted to inhibit the proliferation of hRECs and neovascularization.