# Choroidal Mast Cells and Their Degranulation Are a Pivotal Trigger for Myopia Development

**Authors:** Jue Shi, Shin-ichi Ikeda, Tomokazu Fukuchi, Junhan Chen, Kate Gettinger, Satoshi Imanishi, Kazuno Negishi, Kazuo Tsubota, Toshihide Kurihara

PMC · DOI: 10.1167/iovs.66.14.22 · Investigative Ophthalmology & Visual Science · 2025-11-12

## TL;DR

Choroidal mast cells and their degranulation are shown to play a key role in the development of myopia, offering a new potential treatment target.

## Contribution

This study identifies choroidal mast cell degranulation as a pivotal trigger for myopia progression.

## Key findings

- MC-deficient mice showed suppressed myopia development compared to wild-type mice.
- Injecting mast cells into MC-deficient mice restored myopia progression.
- Mast cell stabilizers inhibited both degranulation and myopia progression.

## Abstract

Mast cells (MCs), key immune regulators, contribute to inflammatory responses through their degranulation. Choroidal thinning is a hallmark of myopia, and MC degranulation has been shown to induce choroidal thinning in a rat model of geographical atrophy. However, the role of choroidal MCs in myopia remains poorly understood. This study aimed to demonstrate that an increased number and proportion of degranulated MCs in the choroid are important determinants of choroidal thinning and myopia development.

Lens-induced myopia (LIM) was induced by monocular −30 diopter (D) lens wearing in C57BL/6 mice, MC-deficient mice (Mcpt5/Cma1DTR/+), and MC-deficient mice receiving suprachoroidal injection of peritoneal MCs (PMCs). Cromolyn sodium (cromolyn) and pemirolast potassium (pemirolast), reagents that inhibit degranulation by stabilizing MC membranes, were topically applied in LIM mice. Ocular parameters including refraction, axial length, and choroidal thickness were measured before and after LIM. Choroidal MC degranulation was evaluated by choroidal flatmount staining.

LIM was successfully induced in wild-type mice but was significantly suppressed in MC-deficient mice. Suprachoroidal injection of PMCs into MC-deficient mice restored myopia progression, as evidenced by axial elongation and choroidal thinning. MC degranulation was significantly increased by −30 D lens wearing, whereas topical administration of cromolyn and pemirolast effectively inhibited both MC degranulation and myopia progression.

Choroidal MC degranulation plays a critical role in LIM by promoting choroidal thinning and axial elongation. These findings enhance our understanding of the role of choroidal MC degranulation in myopia, suggesting a potential therapeutic target for myopia treatment.

## Linked entities

- **Chemicals:** cromolyn sodium (PubChem CID 27503), pemirolast potassium (PubChem CID 443866)
- **Diseases:** myopia (MONDO:0001384)

## Full-text entities

- **Genes:** Cma1 (chymase 1, mast cell) [NCBI Gene 17228] {aka MMCP-5, Mcp-5, Mcp5, Mcpt5}
- **Diseases:** inflammatory (MESH:D007249), LIM (MESH:D007905), geographical atrophy (MESH:D057092), Choroidal thinning (MESH:D013851), Myopia (MESH:D009216)
- **Chemicals:** pemirolast (MESH:C055139), Cromolyn sodium (MESH:D004205)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12614256/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12614256/full.md

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Source: https://tomesphere.com/paper/PMC12614256