Abstract
Purpose::
Proliferative Vitreoretinopathie (PVR) is known as a major complication in retinal detachment surgery and characterized by massive intraretinal and vitreoretinal proliferation. Intraretinal PVR manifests clinically as retinal stiffness, the result of Mueller cell proliferation. Alkylphosphocholines (APCs), used in clinical routine for leishmaniosis and cancer treatment, are effective inhibitors of human ocular cell proliferation and are now to be investigated for their effect on human and rat Mueller cell proliferation.
Methods::
Semiconfluent cultured primary rat Mueller cells (P1-4) and the immortalized human Mueller cell line MIO-M1 (GFAP negative) were incubated with APCs (C18:1-PC or C22:1-PC) in different concentrations (0 - 500 nM) with or without addition of fetal calf serum (10 % FCS) for 24 hrs. Proliferation was assessed with the Tetrazolium dye-Reduction Assay (MTT) and BrdU labelling. Toxicity was measured with the trypan blue exclusion assay.
Results::
APCs inhibit the proliferation of human and rat Mueller glia cells in a dose-dependent manner in non-toxic concentrations. The IC50 concentrations for the different APCs are between a minimum of 10 nM (MIO-M1; C18:1-PC and C22:1-PC; without serum) and a maximum of 100 nM (rat Mueller cells; C18:1-PC and C22:1-PC; 10% FCS). In the presence of serum, more APC is needed to achieve equivalent inhibition of Mueller glia cell proliferation compared to Mueller glia cells without serum.
Conclusions::
APCs are effective inhibitors of human and rat Mueller glia cell proliferation in vitro. Therefore it is tempting to speculate that these novel substances might potentially be able to control intraretinal proliferation, an early stage in PVR pathogenesis and open a new perspective on PVR prevention.
Keywords: Muller cells • proliferation • retinal detachment