Molecular Mechanism of Celastrol Intervening in TFEB-Mediated Lysosomal Biogenesis Dysfunction Inhibiting Cataract Formation

Chunmei QI; Xiuhui LI; Zhihui ZHANG

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Chunmei QI, Xiuhui LI, Zhihui ZHANG. Molecular Mechanism of Celastrol Intervening in TFEB-Mediated Lysosomal Biogenesis Dysfunction Inhibiting Cataract Formation[J]. Journal of Kunming Medical University.

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Chunmei QI, Xiuhui LI, Zhihui ZHANG. Molecular Mechanism of Celastrol Intervening in TFEB-Mediated Lysosomal Biogenesis Dysfunction Inhibiting Cataract Formation[J]. Journal of Kunming Medical University.

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Molecular Mechanism of Celastrol Intervening in TFEB-Mediated Lysosomal Biogenesis Dysfunction Inhibiting Cataract Formation

1.
Department of Ophthalmology and Otorhinolaryngology
2.
Department of Ophthalmology，Kailuan General Hospital Ophthalmology，Tangshan Hebei 063000，China

Received Date: 2025-08-18

Abstract

Abstract

Objective This study aims to investigate whether celastrol （Cel） inhibits cataract formation by activating the transcription factor EB （TFEB）-mediated lysosomal biosynthesis pathway. Methods An oxidative stress model in human lens epithelial cells induced by H₂O₂ and a rat cataract model induced by selenite were employed. Cells were divided into control, model, Cel intervention, Cel + TFEB siRNA, or Cel + MHY1485 groups （n = 5）. 45 neonatal mice were divided into control, model, and Cel intervention groups （n = 9）. Cell viability was assessed by the CCK-8 assay, TFEB nuclear translocation was observed by immunofluorescence staining. Protein expression of LAMP1 and CTSB was detected by Western blot, lysosome quantity was assessed by LysoTracker Red staining. Lens opacity was observed and graded using the Bahmani standard under slit lamp microscopy, and lens morphology was observed by hematoxylin and eosin staining. TFEB siRNA and an mTOR activator （MHY1485） were also used to validate the mechanism of action of Cel. Results Compared with the model group, the Cel intervention group significantly increased TFEB nuclear translocation efficiency by approximately 2.1-fold （P < 0.0001） and significantly upregulated the expression of lysosomal function-related proteins （all P < 0.001）. LysoTracker Red staining showed that Cel intervention group reversed the H₂O₂-induced decrease in lysosome quantity （P < 0.0001）. In the animal model, Cel intervention group significantly reduced lens opacity （P < 0.05）. These positive effects of Cel were significantly antagonized by TFEB siRNA or the mTOR activator MHY1485 （P < 0.001）. Conclusion Cel promotes TFEB nuclear translocation by inhibiting the mTOR signaling pathway, enhances lysosomal biogenesis, improves lens protein homeostasis, and thereby suppresses cataract formation. This study provides a theoretical basis for non-surgical cataract treatment targeting TFEB.
- Celastrol,
- Transcription factor EB,
- Lysosome,
- Cataract,
- mTOR

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References(19)

References

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