Albumin alleviated esketamine-induced neuronal apoptosis of rat retina through downregulation of Zn(2+)-dependent matrix metalloproteinase 9 during the early development

AIMS: Esketamine upregulates Zn(2+)-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 Zn(2+)-dependent MMP9. METHODS: We investigate the role of Zn(2+) 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 Zn(2+) in the retinal GCL during the early development. Zn(2+)-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 Zn(2+) accumulation in GCL and downregulating Zn(2+)-dependent MMP9. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12868-022-00753-5.