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miR-146a is Upregulated During Retinal Pigment Epithelium (RPE)/Choroid Aging in Mice and Represses IL-6 and VEGF-A Expression in RPE Cells

Yi Hao, Qinbo Zhou, Jing Ma, Yun Zhao and Shusheng Wang

Purpose: MicroRNA-146a (miR-146a) has been proposed as a marker for age-associated inflammation, or “inflammaging”, acting as a negative regulator of cellular senescence and pro-inflammatory signalling pathways. However, the regulation and function of miR-146 during ocular aging remains unclear. Here we propose that miR-146 is regulated during aging of the retina and choroid, and functions in retinal pigment epithelial (RPE) cells to regulate key genes involved in inflammation and angiogenesis.
Methods: The expression of miR-146a and miR-146b was examined in the neuroretina and RPE/choroid in mice aged from 2 months to 24 months. Then, the effect of synthetic miR-146a mimetic on IL-6 and VEGF-A expression was analysed in RPE cells treated with and without TNF-α.
Results: miR-146a and miR-146b were upregulated during aging of RPE/choroid but not neuroretina, supporting tissue-specific regulation of aging-related miRNAs in retinal tissues. Overexpression of miR-146a by miRNA mimics inhibited VEGF-A and TNF-α-induced IL-6 expression.
Conclusions: Elevation of miR-146a and miR-146b in the aging RPE/choroid but not neuroretina suggests a role for miRNAs in inflammaging in the RPE/choroid. miR-146a overexpression inhibits the expression IL-6 and VEGF-A in the RPE cells, supporting a negative feedback regulation mechanism that regulates inflammatory pathways during ocular aging.