Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (10): 2109-2120.doi: 10.4103/1673-5374.303537

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Luteolin delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

Xiao-Bin Liu1, Feng Liu1, Yi-Yao Liang1, Gang Yin2, Hui-Jun Zhang3, Xue-Song Mi3, Zai-Jun Zhang2, Kwok-Fai So1, 4, 5, Ang Li1, 4, *, Ying Xu1, 5, *#br#   

  1. 1Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China; 2Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University, Guangzhou, Guangdong Province, China; 3Department of Ophthalmology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China; 4Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province, China; 5Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
  • Online:2021-10-15 Published:2021-03-19
  • Contact: Ying Xu, PhD, xuying@jnu.edu.cn; Ang Li, PhD, anglijnu@jnu.edu.cn.
  • Supported by:
    The work was supported by the National Natural Science Foundation of China, Nos. 81470656 (to YX), 82071372 (to AL), 82074169 (to XSM); Guangdong Grant Key Technologies for Treatment of Brain Disorders’, China, No. 2018B030332001 (to YX); Ningxia Key Research and Development Program Grant (Yinchuan, Ningxia Hui Autonomous Region, China) (to KFS); Program of Introducing Talents of Discipline to Universities, China, No. B14036 (to YX, AL, KFS); Outstanding Scholar Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), No. 2018GZR110102002 (to KFS, AL); and Science and Technology Program of Guangzhou, No. 202007030012 (to KFS and AL).

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Abstract: Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury, whereby it can inhibit microglial neurotoxicity. Therefore, luteolin holds the potential to be useful for treatment of retinal diseases. The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on rod cells in rd10 mice, a slow photoreceptor-degenerative model of retinitis pigmentosa. Luteolin (100 mg/kg) intraperitoneally injected daily from postnatal day 14 (P14) to P25 significantly enhanced the visual performance and retinal light responses of rd10 mice at P25. Moreover, it increased the survival of photoreceptors and improved retinal structure. Mechanistically, luteolin treatment attenuated increases in reactive oxygen species, photoreceptor apoptosis, and reactive gliosis; increased mRNA levels of anti-inflammatory cytokines while lowering that of pro-inflammatory and chemoattractant cytokines; and lowered the ratio of phospho-JNK/JNK. Application of the JNK inhibitor SP600125 exerted a similar protective effect to luteolin, suggesting that luteolin delays photoreceptor degeneration and functional deterioration in rd10 mice through regulation of retinal oxidation and inflammation by inhibiting the JNK pathway. Therefore, luteolin may be useful as a supplementary treatment for retinitis pigmentosa. This study was approved by the Qualified Ethics Committee of Jinan University, China (approval No. IACUC-20181217-02) on December 17, 2018.

Key words: anti-inflammation, apoptosis, flavonoid, JNK pathway, luteolin, photoreceptor, reactive gliosis, reactive oxygen species, retinal degeneration, retinitis pigmentosa

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