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Investigation of the therapeutic mechanism of subthreshold micropulse laser irradiation in retina

  • Basic Science
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Abstract

Purpose

Subthreshold micropulse laser irradiation has been used for the treatment of retinal edema; however, there are few reports about the mechanism of its therapeutic effect. In this study, we compared threshold short pulse and subthreshold micropulse laser irradiation in mice and investigated their mechanism.

Methods

Nine to 12-week-old male C57BL/6J mice were used in this study. After general anesthesia, threshold short pulse or subthreshold micropulse laser irradiation was performed on the right eye using IQ577. Enucleation was performed 24 h after the laser irradiation, and histological and gene expression analyses were carried out.

Results

Coagulation spots and atrophy of the retinal pigment epithelium were observed after threshold short pulse laser irradiation but not after subthreshold micropulse laser irradiation. Twenty-four hours after laser, aquaporin (AQP) 1, 2, 7, and 11 levels were significantly elevated by 1.7- to 3-fold in the threshold short pulse laser group compared with non-treated control group. AQP 3 was increased significantly and prominently by 100-fold. VEGF-A and VEGFR2 were upregulated 1.5- and 2.3-fold, respectively. In the subthreshold micropulse laser group, AQP 3 was increased by 6-fold compared with the non-treated control group. Angiopoietin-1 and the adrenomedullin (AM) receptor CLR were decreased by 0.6-fold and 0.5-fold, respectively.

Conclusion

Threshold short pulse laser irradiation caused retinal damage and prominent changes in the expression of various genes. Contrarily, subthreshold micropulse laser irradiation did not induce retinal damage; it upregulated AQP 3, which might have improved retinal edema by drainage of subretinal fluid.

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Funding

This study was supported by Grants-in-Aid for Scientific Research (KAKENHI), Core Research for Evolutionary Science and Technology (CREST) of the Japan Science and Technology Agency (JST), and the Japan Agency for Medical Research and Development (AMED), and research grants from Bristol-Myers Squibb Company, the Japan Foundation for Applied Enzymology, the Naito Foundation, the Public Foundation of Chubu Science and Technology Center, Yamaguchi Endocrine Research Foundation, Hoyu Science Foundation, Takahashi Industrial and Economic Research Foundation, Akaeda Medical Research Foundation, Shinshu Public Utility Foundation for Promotion of Medial Sciences, NOVARTIS Foundation (Japan) for the Promotion of Science grant, and Japan Heart Foundation to TS.

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Authors and Affiliations

  1. Department of Ophthalmology, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, 390-8621, Japan

    Kazutaka Hirabayashi, Shinji Kakihara, Masaaki Tanaka & Toshinori Murata

  2. Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan

    Shinji Kakihara, Masaaki Tanaka & Takayuki Shindo

  3. Department of Life Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Nagano, Japan

    Takayuki Shindo

Authors
  1. Kazutaka Hirabayashi
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  2. Shinji Kakihara
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  3. Masaaki Tanaka
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  4. Takayuki Shindo
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  5. Toshinori Murata
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by KH, SK, and MT. The first draft of the manuscript was written by KH, and all authors commented on previous versions of the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Kazutaka Hirabayashi.

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Ethical approval

All animal handling procedures were in accordance with a protocol approved by the Ethics Committee of Shinshu University School of Medicine No.280079. All experiments were performed in accordance with the Association for Research in Vision and Ophthalmology’s Statement for the Use of Animals in Ophthalmic and Vision Research and our institutional guidelines.

Conflict of interest

TM received financial support from Novartis. All other authors report that they have no conflict of interest.

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Hirabayashi, K., Kakihara, S., Tanaka, M. et al. Investigation of the therapeutic mechanism of subthreshold micropulse laser irradiation in retina. Graefes Arch Clin Exp Ophthalmol 258, 1039–1047 (2020). https://doi.org/10.1007/s00417-020-04638-3

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  • DOI: https://doi.org/10.1007/s00417-020-04638-3

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