The Role Of C5a In Proliferative Vitreoretinopathy

BACKGROUND: Proliferative vitreoretinopathy(PVR) is an intraocular wound healing response involved in several lines of cells and a number of cytokines, and the common cause of failure in treatment of retinal datachment. retinal pigment epithelial(RPE) cells play an important role in PVR. The anaphylatoxin, complement 5a (C5a), plays a key role in mediating various inflammatory reactions following complement activation. C5a is a multipotential cytokine,which can produce a range of responses in target cells. As a potent mediator of inflammation ,C5a exerts its actions through activation of the C5a receptor (C5aR).and transmits its mutifuctional signals such as anaphylatoxin, immune regulation, chemotactic activity.Aim: This study consists of two parts: 〤5a anaphylatoxin is a potent inflammatory mediator that acts on polymorphonuclear cells (PMN) and monocytes via C5a receptors (C5aR). It mediates chemotaxis of both cell types and stimulates cytokine release from the latter. To investigate whether C5a can act on retinal pigment epithelial (RPE) cells, we examined human retinal pigment epithelial cells for the presence of C5aR to observe the expression and distribution of C5a receptor (C5aR) on epiretinal membranes (ERM) tissue from patients with proliferative retreous body-retina ( PVR) lesion and cultured retinal pigmentary epithelial (RPE) cells. ㏕o observe whether C5a can induce increased expression of IL-6s IL-8.Methods:(1)The immunohistochemical technique was used to evaluate the expression of C5aR in human epiretinal membranes complicated with PVR which were obtained from eye undergone vitrectomy and curtured RPE cells. (2)To document that the increases did result in increased cytokine production, two representative cytokines, IL-6 and IL-8 were studied. Foreach cytokine, protein levels released in the culture supernatant after stimulation by C5a were measured by specific sandwich ELISA.Result : (1) in 7 membranes of PVR-grade C, C5aR was expressed in 5(71.4%),And in 6 cases it was detegted in 8 membranes of PVR-grade D (75%). No significant differences were found between PVR-grade C and PVR-gradeD in expression of C5aR(P>0.05). The expression of C5aR was detected readily in RPE cells. (2)we found that C5a induces increased expression of IL-6, IL-8 as well as in macrophages. the kinetics of maximum expression of each cytokine differed. The maximum increase of IL-8 was observed at 8 h, that of IL-6 at 4 h.Conclution:(1)The expression of C5aR in epiretinal membranes and cultured RPE indicates that C5a may be involved in epiretinal membranes and development of epiretinal membranes . C5a may play an important role in the development of PVR (2)The induction of IL-8, IL-6 upon C5a stimulation suggests that C5a may participate in the defense of choroidal and retinal tissue during inflammation.