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Mertk deficiency alters expression of micrornas in the retinal pigment epithelium cells

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Abstract

Phagocytic clearance of the spent photoreceptor outer segments (OS) by RPE cells is regulated by circadian rhythm cycle and is essential for photoreceptor integrity and function. Mertk regulates RPE phagocytosis and a deficiency in Mertk causes photoreceptor degeneration and visual loss. This study aimed to investigate Mertk regulation of the microRNAs (miRNA), potentially regulating expression of their target genes, which affect phagocytosis. The differentially expressed miRNAs were identified using miRCURYTM microRNA Arrays from total RNA isolated at 0900 h and 1900 h from the mechanically dissociated RPE sheets of the WT and Mertk −/− mice, which were housed in a 12-h light-dark cycle with the lighting onset at 0700 h (7:00am). Validation of the differentially expressed miRNAs and assessment of the putative miRNA target gene expression were performed by real-time PCR. Among the differentially expressed miRNAs in the Mertk −/− RPE, seven miRNAs were up-regulated and 13 were down-regulated in the morning groups. Similarly, 24 miRNAs were found to be up-regulated and 13 were down-regulated in the evening groups. To search for those that may participate in regulating expression of cytoskeletal proteins, we examined the predicted target genes that might participate in phagocytosis were examined by real-time PCR. Of nine potential altered targets, four deregulated genes were myosin subunits. Notably, multiple members of the 21 up-regulated miRNAs can theoretically recognize these down-regulated mRNAs, particularly MyH14 and Myl3. This study shows that loss of Mertk alters miRNA expression, which in turn affects expression of the downstream target genes, potentially affecting phagocytosis.

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Acknowledgments

This paper was supported by NIH grants R01EY018830 and Research to Prevent Blindness.

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Authors and Affiliations

  1. Faculty of Basic Medical Science, Capital Medical University, Beijing, 100069, China

    Yong Tang, Qingjun Lu, Yunrong Wei, Lixia Han & Qingxian Lu

  2. Beijing Institute of Ophthalmology, Beijing, China

    Qingjun Lu

  3. Beijing Tong-Ren Eye Center, Beijing Tong-Ren Hospital, Capital Medical University, Beijing, 100069, China

    Qingjun Lu

  4. Department of Ophthalmology and Visual Sciences; Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY, 40202, USA

    Rui Ji, Qiutang Li & Qingxian Lu

  5. University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY, 40202, USA

    Qingxian Lu

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  1. Yong Tang
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  2. Qingjun Lu
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  3. Yunrong Wei
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  4. Lixia Han
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Correspondence to Qingxian Lu.

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Tang, Y., Lu, Q., Wei, Y. et al. Mertk deficiency alters expression of micrornas in the retinal pigment epithelium cells. Metab Brain Dis 30, 943–950 (2015). https://doi.org/10.1007/s11011-015-9653-5

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  • DOI: https://doi.org/10.1007/s11011-015-9653-5

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