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Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
Diosgenin Attenuates Photoreceptor Degeneration in an N-Methyl-N-Nitrosourea-Induced Mouse Model of Retinal
Wanqing Tong1,2,3, Jinfeng Cao1,2,3, Xuebin Zhou1,2,3
1Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China.
Purpose:
Retinitis pigmentosa (RP) is a hereditary retinal disorder distinguished by progressive photoreceptor cell (PRC) loss, in which glial activation can accelerate degeneration. Diosgenin, a natural steroidal sapogenin with potent anti-inflammatory properties, has shown therapeutic potential for ocular and neurodegenerative diseases but has not been explored for retinal degeneration. This study examined the protective role of diosgenin against PRC degeneration and explored potential anti-inflammatory mechanisms in an N-methyl-N-nitrosourea (MNU)-induced mouse model of retinal degeneration.
Methods:
The model was established by intraperitoneal injection of 50 mg/kg MNU, followed by oral gavage of diosgenin/lutein (positive control)/vehicle. The effects of diosgenin on PRC structure, apoptosis, retinal function, and glial activation were evaluated. Network pharmacology and molecular docking were used to investigate potential mechanisms.
Results:
Diosgenin preserved retinal integrity and function in MNU-induced mice, with relative preservation of the outer nuclear layer thickness and outer segment (OS) length of rods and cones. Disorganization of OS membrane discs and abnormal morphology of organelles were attenuated, while fundus photographs showed fewer lesions. Furthermore, diosgenin mitigated PRC apoptosis and maintained retinal light responses. Mechanistically, diosgenin ameliorated reactive gliosis of Müller glial cells (MGCs), attenuated the expression levels of inflammatory cytokines and chemokines, and mitigated activation of the IL6ST/JAK2/STAT3 pathway.
Conclusions:
Diosgenin attenuated PRC degeneration in MNU-induced mice, and one of its mechanisms may involve the attenuation of reactive gliosis in MGCs and inflammatory responses, with possible involvement of the IL6ST/JAK2/STAT3 pathway. Diosgenin may serve as a potential intervention candidate for retinal degenerative diseases, such as RP.
