Isolation of three different sizes of exosomes in an Asian population with different retinal diseases before and after treatment: preliminary results

ABSTRACT

Exosomes are membranous structures measuring between 40–120 nm that are secreted by various cells of the human body into the body fluid system. Exosomes contain proteins, mRNA, miRNA, and signaling molecules, and physiologically they assist in the intercellular transport of proteins and RNA molecules. In this study, we used an immunoaffinity filter paper platform combined with scanning electron microscopy and microfluidic systems to detect the size of exosomes within the aqueous humor. Eight aqueous humor samples showed three distinct sizes of exosomes that were significantly different on scanning electron microscopy(P < 0.01). We further used nanoparticle tracking analysis to assess the size distribution of exosomes within the aqueous humor. We found significantly different distributions of exosomes between patients with three different ocular diseases and patients with normal cataracts as controls. An obvious peak of exomeres(size around 35 nm)was found in the patients with central retinal vein occlusion and vitreous hemorrhage. Flare-ups of large exosomes(size 90–120 nm)were found in the patients with the inflammatory ocular disease pars planitis. No obvious peaks in exomeres or large exosomes were found in the control group. There was a high association between the distribution of exosomes and the pathogenesis of ocular diseases. After intravitreal anti-vascular endothelial growth factor treatment, the aqueous humor from the patients with neovascular diseases showed a significant reduction in exosomes in nanoparticle tracking analysis. These findings suggest that at least three distinct sizes of exosomes exist in the aqueous humor:(1)exomeres:<35 nm;(2)small exosomes:60–80 nm; and (3)large exosomes:90–120 nm. Different sizes of exosomes may have different implications in normal or diseased eyes.

Research Highlights

• Three different sized exosomes were identified in aqueous humor.

• The distribution of exosome size was significantly different between the patients with inflammatory and neovascularization retinal diseases.

• After intravitreal anti-vascular endothelial growth factor treatment, the aqueous humor from patients with neovascular diseases showed a significant reduction in exosomes in nanoparticle tracking analysis.

Graphical Abstract

KEYWORDS:

• Exosome
• aqueous humor
• nanoparticle tracking analysis
• ocular disease
• exomere

Acknowledgments

We thank Dr. Yu-Ping Wang (Department of Radiology, Chiayi Branch, Taichung Veterans General Hospital) for his assistance in creating the illustration for the Graphical Abstract. We also thank ATS Medical Editing for editing the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization: Sung-Yu Wu, Connie Chen, Chao-Min Cheng, Chihchen Chen, Min-Yen Hsu; Investigation: Jyh-Cheng Liou, Sung-Yu Wu, Yu-Chien Hung, Chao-Min Cheng, Chihchen Chen, Min-Yen Hsu; Drafting and Writing the Manuscript: Sung-Yu Wu, Yu-Chien Hung, Connie Chen, Min-Yen Hsu; Funding acquisition: Min-Yen Hsu.

Availability of data and material

The data that support the findings of this study are available on request from the corresponding author.

Ethics approval and consent to participate

This study was approved by the review board of the Ethics Committee of Chung Shan Medical University Hospital [IRB number: CSMUH No: CS2–19048]. Informed consent was obtained from all participants included in this study.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21655979.2023.2297320

Additional information

Funding

This study was supported in part by intramural grants from Chung Shan Medical University Hospital [Grant No. CSH-2022-C-003], and the National Science and Technology Council of Taiwan (111-2636-E-040-001, Columbus program of MOST Young Scholar Fellowship; 111-2314-B-040-026-MY2).