Abstract
Purpose :
The cGAS-STING pathway plays an important role in innate immunity. Previous studies have shown that activation of cGAS-STING is implicated in AMD pathogenesis. Whether this pathway plays a role during lens development remains elusive. In the present study, we have analyzed the developmental expression patterns of the major signal components of the cGAS-STING pathway and revealed its potential role in governing lens development.
Methods :
Normal mouse embryos of different stages and adult mice were used for isolation of eye tissues. RT-PCR and in situ hybridization were used to analyze the mRNA expression levels of cGAS, STING, TBK1 and IRF3. Immunohistochemistry was used to detect the protein expression levels of the above components.
Results :
At the mRNA level, cGAS and TBK1 mRNAs were detected at ED 14.5, reached the highest expression levels in the newborn lens and then were downregulated to 60-70% in the mature lens, and were further downregulated during aging in 7- to 8-month. In contrast, expression of the STING mRNA was low at the ED14.5, and gradually upregulated in newborn and adult mouse lenses and further upregulated in the aging lens. Different from cGAS, TBK1 and STING, the IRF3 mRNA was low at the ED 14.5, then upregulated in the newborn lens and maintained at this level in the mature and aging lens. At the protein level, the cGAS signal was relatively weak. The STING signal was very strong from ED 11.5 to newborn mice, and the IRF3 signal was intermediate between cGAS and STING.
Conclusions :
The signal components of the cGAS/STING pathway are clearly expressed during lens development. Activation of this pathway may be important to protect lens development. Supported by National Natural Science Foundation of China (Grants 81970787, 82000876, 81770910) and Natural Science Foundation of Guangdong Province and Guangdong City Joint Program of China (2019B1515120014)，and the Fundamental Funds, 3030901010110 of the State Key Laboratory of Ophthalmology of Zhongshan Ophthalmic Center.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.