Albumin alleviated esketamine-induced neuronal apoptosis of rat retina through downregulation of Zn2+-dependent matrix metalloproteinase 9 during the early development

Abstract

Aims: Esketamine upregulates Zn²⁺-dependent matrix metalloproteinase 9 (MMP9) and increases the neuronal apoptosis in retinal ganglion cell layer during the early development. We aimed to test whether albumin can alleviate esketamine-induced apoptosis through downregulating Zn²⁺-dependent MMP9.

Methods: We investigate the role of Zn²⁺ in esketamine-induced neuronal apoptosis by immunofluorescence. MMP9 protein expression and enzyme activity were investigated by zymography in situ., western blot and immunofluorescence. Whole-mount retinas from P7 Sprague-Dawley rats were used.

Results: We demonstrated that esketamine exposure increased Zn²⁺ in the retinal GCL during the early development. Zn²⁺-dependent MMP9 expression and enzyme activity up-regulated, which eventually aggravated apoptosis. Albumin effectively down-regulated MMP9 expression and activity via binding of free zinc, ultimately protected neurons from apoptosis. Meanwhile albumin treatment promoted activated microglia into multi-nucleated macrophagocytes and decreased the inflammation.

Conclusion: Albumin alleviates esketamine-induced neuronal apoptosis through decreasing Zn²⁺ accumulation in GCL and downregulating Zn²⁺-dependent MMP9.

Keywords: Albumin; Apoptosis; Esketamine; Matrix metalloproteinase 9; Zn2+.