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Age and light damage influence Fzd5 regulation of ocular growth-related genes
Shanzhen Peng1, Mingzhu Guo1, Cheng Wu1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Abstract:
Genetic and environmental factors can independently or coordinatively drive ocular axis growth. Mutations in FRIZZLED5 (FZD5) have been associated with microphthalmia, coloboma, and, more recently, high myopia. The molecular mechanism of how Fzd5 participates in ocular growth remains unknown. In this study, we compiled a list of human genes associated with ocular growth abnormalities based on public databases and a literature search. We identified a set of ocular growth-related genes from the list that was altered in the Fzd5 mutant mice by RNAseq analysis at different time points. The Fzd5 regulation of this set of genes appeared to be impacted by age and light damage. Further bioinformatical analysis indicated that these genes are extracellular matrix (ECM)-related; and meanwhile an altered Wnt signaling was detected. Altogether, the data suggest that Fzd5 may regulate ocular growth through regulating ECM remodeling, hinting at a genetic-environmental interaction in gene regulation of ocular axis control.
Insights
Mutations in FRIZZLED5 (FZD5) impact ocular growth by altering extracellular matrix remodeling. This suggests a genetic-environmental interaction in controlling eye axis development, potentially influencing conditions like high myopia.
Area of Science:
- Genetics
- Developmental Biology
- Ophthalmology
Background:
- Ocular axis growth is influenced by genetic and environmental factors.
- Mutations in FRIZZLED5 (FZD5) are linked to eye abnormalities including high myopia.
- The precise molecular role of Fzd5 in ocular development is not fully understood.
Purpose of the Study:
- To investigate the molecular mechanism by which Fzd5 influences ocular growth.
- To identify genes regulated by Fzd5 in the context of eye development.
- To explore potential genetic-environmental interactions in Fzd5-mediated ocular growth control.
Main Methods:
- Compiled a list of human ocular growth abnormality genes from public databases and literature.
- Performed RNA sequencing on Fzd5 mutant mice at various time points.
- Utilized bioinformatical analysis to identify gene functions and signaling pathways.
Main Results:
- Identified a set of ocular growth-related genes altered in Fzd5 mutant mice.
- Found that Fzd5 regulation of these genes is affected by age and light damage.
- Bioinformatic analysis revealed these genes are extracellular matrix (ECM)-related and associated with altered Wnt signaling.
Conclusions:
- Fzd5 may regulate ocular axis growth by modulating ECM remodeling.
- The findings suggest a role for Fzd5 in genetic-environmental interactions governing eye development.
- This research provides insights into the molecular basis of myopia and other ocular growth disorders.

