Purpose: Glaucoma is a progressive optic neuropathy characterized by loss of retinal ganglion cells (RGC) and optic nerve degradation. Existing treatments focus on lowering intraocular pressure (IOP); however, vision loss may still progress. Neuroprotectant drugs are useful as an adjunct approach in preventing further loss of RGCs; though, candidate genes are lacking. FK506, a widely used immunosuppressant drug, has profound neuroprotective and neuroregenerative properties throughout the central nervous system, including the eye. FK506 achieves these properties through interaction with FK506 Binding Proteins (FKBP). In this study, we investigate FKBP51s neuroprotective properties.
Methods: Retinal ganglion cells (RGC-5s) were stably transfected with FKBP51 overexpression vector. Cells were subjected to excitatory glutamate toxicity. Cell death was measured through calcein-AM/propidium iodide cell-survival assay. Western blot analysis was used to determined cytochrome c release from the mitochondria during apoptosis.
Results: In RGC-5 cell cultures, stably transfected cells overexpressing FKBP51 showed increased cell viability during calcein-AM/propidium iodide cell-survival assay compare to negative control. Furthermore, RGC-5 cells overexpressing FKBP51 had a decrease in cytochrome c release into the cytosol and an increase of cytochrome c in the mitochondria.
Conclusions: These data provide strong evidence that FKBP51 promotes anti-apoptotic action in retinal ganglion cells during excitatory glutamate toxicity. Further investigation is needed to determine which pathways FKBP51 activates to achieve these neuroprotective action.