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Profiling miRNAs in tear extracellular vesicles: a pilot study with implications for diagnosis of ocular diseases

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Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To estimate the roles of extracellular vesicles (EVs) in tears and to determine whether their profiles are associated with the type of ocular disease.

Study design

Cross-sectional study.

Methods

Tear EVs were extracted from 14 healthy participants and from 21 patients with retinal diseases (age-related macular degeneration [AMD] or diabetic macular edema [DME]). The surface marker expression of tear EVs was examined, and microRNAs (miRNAs) were extracted and profiled by use of real-time PCR array. The stability of the expression of the miRNAs was determined, and their functions were assessed by network analyses. Classification accuracy was evaluated by use of a random forest classifier and k-fold cross-validation.

Results

The miRNAs that were highly expressed in tear EVs were miR-323-3p, miR-548a-3p, and miR-516a-5p. The most stably expressed miRNAs independent of diseases were miR-520h and miR-146b-3p. The primary networks of the highly stably expressed endogenous miRNAs were annotated as regulation of organismal injury and abnormalities. The highly expressed miRNAs for severe retinal disease were miR-151-5p for AMD and miR-422a for DME, suggesting potential roles of tear EVs in liquid biopsy. Nine miRNAs (miR-25, miR-30d, miR-125b, miR-132, miR-150, miR-184, miR-342-3p, miR-378, and miR-518b) were identified as distinguishing individuals with AMD from healthy individuals with a classification accuracy of 91.9%.

Conclusions

The finding that tear EVs contain characteristic miRNA species indicates that they may help in maintaining homeostasis and serve as a potential tool for disease diagnosis.

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Acknowledgements

Ryu Uotani reports a relationship with the Japanese Ministry of Education, Science, and Culture that includes funding grants.

Author information

Authors and Affiliations

  1. Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori, 683-8504, Japan

    Airu Torimura, Saki Kanei, Yumiko Shimizu, Takashi Baba, Ryu Uotani, Shin-ichi Sasaki, Daisuke Nagase, Yoshitsugu Inoue & Dai Miyazaki

  2. Department of Molecular and Cellular Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Takahiro Ochiya

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  1. Airu Torimura
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Correspondence to Dai Miyazaki.

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Conflict of interest

A. Torimura, None; S. Kanei, None; Y. Shimizu, None; T. Baba, None; R. Uotani, None; S. Sasaki, None; D. Nagase, None; Y. Inoue, None; T. Ochiya, Patent application filed for the Exoscreen; D. Miyazaki, None.

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Corresponding Author: Dai Miyazaki

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Torimura, A., Kanei, S., Shimizu, Y. et al. Profiling miRNAs in tear extracellular vesicles: a pilot study with implications for diagnosis of ocular diseases. Jpn J Ophthalmol 68, 70–81 (2024). https://doi.org/10.1007/s10384-023-01028-0

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  • DOI: https://doi.org/10.1007/s10384-023-01028-0

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