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

Abstract

<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Albumin alleviates esketamine-induced neuronal apoptosis through decreasing Zn²⁺ accumulation in GCL and downregulating Zn²⁺-dependent MMP9.

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