Related Experiment Video
Updated: Jul 4, 2025
Transpupillary Two-Photon In Vivo Imaging of the Mouse Retina
Published on: February 13, 2021
Dysregulation of the circRNA_0087207/miR-548c-3p/PLSR1-TGFB2 axis in Leber hereditary optic neuropathy in vitro
Yi-Ping Yang1,2, Yuh-Lih Chang3,4, Guang-Yuh Chiou5,6
1School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
Background:
Leber hereditary optic neuropathy (LHON) is mainly the degeneration of retinal ganglion cells (RGCs) associated with high apoptosis and reactive oxygen species (ROS) levels, which is accepted to be caused by the mutations in the subunits of complex I of the mitochondrial electron transport chain. The treatment is still infant while efforts of correcting genes or using antioxidants do not bring good and consistent results. Unaffected carrier carries LHON mutation but shows normal phenotype, suggesting that the disease's pathogenesis is complex, in which secondary factors exist and cooperate with the primary complex I dysfunction.
Methods:
Using LHON patient-specific induced pluripotent stem cells (iPSCs) as the in vitro disease model, we previously demonstrated that circRNA_0087207 had the most significantly higher expression level in the LHON patient-iPSC-derived RGCs compared with the unaffected carrier-iPSC-derived RGCs. To elaborate the underlying pathologies regulated by circRNA_008720 mechanistically, bioinformatics analysis was conducted and elucidated that circRNA_0087207 could act as a sponge of miR-548c-3p and modulate PLSCR1/TGFB2 levels in ND4 mutation-carrying LHON patient-iPSC-derived RGCs.
Results:
Using LHON iPSC-derived RGCs as the disease-based platform, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on targeted mRNA of miR-548c-3p showed the connection with apoptosis, suggesting downregulation of miR548c-3p contributes to the apoptosis of LHON patient RGCs.
Conclusion:
We showed that the downregulation of miR548c-3p plays a critical role in modulating cellular dysfunction and the apoptotic program of RGCs in LHON.
Insights
Downregulation of miR-548c-3p contributes to retinal ganglion cell (RGC) apoptosis in Leber hereditary optic neuropathy (LHON). This finding offers new insights into LHON pathogenesis and potential therapeutic targets for vision loss.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- Leber hereditary optic neuropathy (LHON) involves retinal ganglion cell (RGC) degeneration, linked to mitochondrial complex I dysfunction.
- Current LHON treatments are limited, and disease complexity suggests secondary factors contribute to pathogenesis.
- Unaffected carriers highlight the intricate nature of LHON, involving more than just primary genetic defects.
Purpose of the Study:
- To investigate the role of circRNA_0087207 in LHON pathogenesis using patient-derived induced pluripotent stem cells (iPSCs).
- To elucidate the molecular mechanisms by which circRNA_0087207 influences RGCs in LHON.
- To identify key molecular players, such as microRNAs, involved in LHON-associated RGC apoptosis.
Main Methods:
- Utilized LHON patient-specific iPSCs differentiated into RGCs as an in vitro disease model.
- Performed bioinformatics analysis to identify interactions between circRNA_0087207 and microRNAs.
- Conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on miR-548c-3p targets to assess functional implications.
Main Results:
- circRNA_0087207 was significantly upregulated in LHON patient-derived RGCs compared to unaffected carriers.
- circRNA_0087207 acts as a sponge for miR-548c-3p, modulating PLSCR1/TGFB2 levels in LHON RGCs.
- KEGG pathway analysis indicated a link between miR-548c-3p targets and apoptosis, suggesting its downregulation contributes to RGC death in LHON.
Conclusions:
- Downregulation of miR-548c-3p is a critical factor in LHON pathogenesis.
- miR-548c-3p dysregulation contributes to cellular dysfunction and apoptosis in LHON RGCs.
- Understanding the miR-548c-3p pathway may reveal novel therapeutic strategies for LHON-induced vision loss.
