Ocular Matrix Metalloproteinases in Spaceflight

INTRODUCTION: Spaceflight presents unique challenges to ocular health, as visual disturbances such as dry eye symptoms have been frequently reported by astronauts. Matrix metalloproteinases (MMPs), a family of extracellular matrix-degrading enzymes, are known mediators of ocular surface inflammation and tissue remodeling on Earth, particularly in dry eye disease. This review explores the potential role of MMPs in spaceflight-associated ocular conditions, including spaceflight-associated dry eye syndrome and spaceflight-associated neuro-ocular syndrome. METHODS: We searched literature on topics relating to metallomatrix proteins and spaceflight using databases PubMed, MedLine, Embase, and Central from inception to April 2025. RESULTS: Although there are limited studies on direct measurements of tear MMPs during spaceflight, indirect clinical evidence and analog studies suggest that microgravity, radiation, and systemic inflammation may upregulate MMP expression. This contributes to epithelial barrier disruption and impaired wound healing. Rodent models and simulated microgravity experiments further support the mechanosensitive regulation of MMPs across various tissues. DISCUSSION: Given the safety and accessibility of tear collection, MMPs may be useful biomarkers for assessing ocular and systemic changes in astronauts. Understanding MMP expression and regulation in space may inform preventive strategies to preserve vision during long-duration missions. Stephanian B, Ong J, Lee R, Gibson R, Berdahl J, Waisberg E, Mader TH, Lee AG. Ocular matrix metalloproteinases in spaceflight. Aerosp Med Hum Perform. 2026; 97(1):47-54.