Insights into the liver-eyes connections, from epidemiological, mechanical studies to clinical translation

Abstract Maintenance of internal homeostasis is a sophisticated process, during which almost all organs get involved. Liver plays a central role in metabolism and involves in endocrine, immunity, detoxification and storage, and therefore it communicates with distant organs through such mechanisms to regulate pathophysiological processes. Dysfunctional liver is often accompanied by pathological phenotypes of distant organs, including the eyes. Many reviews have focused on crosstalk between the liver and gut, the liver and brain, the liver and heart, the liver and kidney, but with no attention paid to the liver and eyes. In this review, we summarized intimate connections between the liver and the eyes from three aspects. Epidemiologically, we suggest liver-related, potential, protective and risk factors for typical eye disease as well as eye indicators connected with liver status. For molecular mechanism aspect, we elaborate their inter-organ crosstalk from metabolism (glucose, lipid, proteins, vitamin, and mineral), detoxification (ammonia and bilirubin), and immunity (complement and inflammation regulation) aspect. In clinical application part, we emphasize the latest advances in utilizing the liver-eye axis in disease diagnosis and therapy, involving artificial intelligence-deep learning-based novel diagnostic tools for detecting liver disease and adeno-associated viral vector-based gene therapy method for curing blinding eye disease. We aim to focus on and provide novel insights into liver and eyes communications and help resolve existed clinically significant issues.