Reciprocal Inhibitions of HRP and REC in a Coculture System

One of the earliest hallmarks of diabetic retinopathy (DR) is the loss of retinal pericytes. Human retinal pericytes (HRP) are contractile cells that share a common basement membrane with retinal endothelial cells (REC). HRP envelop the REC to maintain tubular integrity and control the hydrostatic pressure of microcirculation. The loss of HRP leads to the development of advanced-stage DR pathology including angiogenesis. However, the mechanism of mutual cell support or inhibition remains unclear. In the present study, HRP and REC were evaluated for cell growth in a coculture system. Results from a monoculture system show that HRP had a shorter doubling time (DT) than REC, based on their growth curves (DT: 34 hr for HRP, 56 hr for REC). When HRP were cocultured with REC, DT of HRP increased from 34 hr (in the monoculture system) to 45 hr (in a coculture system). Similarly, when REC were cocultured with HRP, the DT of REC also increased from 56 hr to 77 hr. These results provide strong evidence for reciprocal inhibitions between HRP and REC in a coculture system. As HRP dropout occurs at the early stage of DR, the elimination of HRP inhibition on REC may lead to REC proliferation, ahead of the action of VEGF from retinal ischemia. Additional experiments that investigate the effects of the interactions of cocultured HRP and REC are expected to uncover details for further insight into the role of REC and HRP on DR.

Keywords: Coculture, Diabetic Retinopathy, Reciprocal Inhibitions.