Indirubin alleviates retinal neurodegeneration through the regulation of PI3K/AKT signaling

Abstract

Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries, including glaucoma, diabetic retinopathy, traumatic optic neuropathy and optic neuritis, etc. The current clinical treatment is not very effective. We investigated indirubin, one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill, in the present study for its role in retinal neurodegeneration. Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro. Moreover, indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo. Furthermore, indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro. In addition, indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress. Mechanically, indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling. In conclusion, indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury. The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.

Keywords

retinal neurodegenerative disease / oxidative stress / PI3K/AKT / retinal ganglion cell / apoptosis

Fundings

This work was generously supported by grants from the National Natural Science Foundation of China (Grant Nos. 81970823 and 82271107) and the Natural Science Foundation of Jiangsu Province (Grant No. BK20221186).

Acknowledgments

We thank the Affiliated Eye Hospital, Nanjing Medical University for their skilled technical assistance.

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