Dexmedetomidine protects high-glucose induced apoptosis in human retinal pigment epithelial cells through inhibition on p75(NTR).

BACKGROUND

In both human patients and animals, diabetic condition of high blood glucose induced significant apoptotic responses in retinal pigment epithelial (RPE) cells. In this work, we used an in vitro culture model of human ARPE-19 cells to evaluate whether dexmedetomidine (DEX) may protect high d-glucose (DG)-induced diabetic apoptosis.

METHODS

ARPE-19 cells were incubated with DG in vitro to induce apoptosis. Cells were also pre-incubated with different concentrations of DEX prior to DG treatment. The apoptotic injury by DG, and possible protection by DEX were evaluated using a TUNEL assay. Western blot assay was used to evaluate DEX-associated signaling pathway proteins, including Casp-3, precursor of the nerve growth factor (proNGF) and p75 neurotrophin receptor (p75(NTR)). Moreover, p75(NTR) was overexpressed in ARPE-19 cells, to assess its mechanistic role in DEX-mediated protection on DG-induced apoptosis.

RESULTS

In ARPE-19 culture, DG induced significant apoptosis, which was protected by pre-incubation of DEX, in a concentration-dependent manner. DG-induce apoptosis was associated with protein upregulation of Casp-3, proNGF and p75(NTR). Among them, Casp-3 and p75(NTR) were inversely reduced by DEX pre-incubation, but not proNGF. In ARPE-19 cells, p75(NTR) overexpression was shown to reverse the protective effect of DEX on DG-induced apoptosis.

CONCLUSION

DEX was proven to have protective effect on DG-induced RPE apoptosis, possible through inhibition on p75(NTR) and its associated signaling pathways.