The potential role of adipokines and hepatokines in age-related ocular diseases

Age-related ocular diseases, including diabetic retinopathy (DR), age-related macular degeneration (AMD), cataract and glaucoma may lead to visual impairment and even to blindness. Metabolic diseases, such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as potential risk factors of age-related ocular diseases, especially DR. Visceral adiposity has been associated with increased risk of DR and AMD in most clinical studies, although body mass index has to-date provided conflicting association with DR and AMD. In addition, obesity is recognized as a risk factor of cataract and glaucoma. Similarly to obesity, MASLD appears to be associated with DR in patients with type 1 diabetes mellitus, but probably not in those with type 2 diabetes mellitus. A potential positive association between MASLD and AMD, glaucoma and cataract is supported by limited evidence to-date, thus needing further investigation. Altered secretion patterns of adipokines (adiponectin, leptin, lipocalin-2, resistin) and hepatokines [adropin, fetuin-A, fibroblast growth factor (FGF)-21, retinol binding protein (RBP)-4] seem to disrupt ocular homeostasis and contribute to the development of age-related ocular diseases in the context of obesity and MASLD. In this regard, novel adipokine-based and hepatokine-based therapies may be added to the treatment options for ocular diseases in the future. This narrative review aimed to summarize evidence on the interconnection of obesity and MASLD with age-related ocular diseases, with a specific focus on the roles of adipokines and hepatokines as mediators of these potential associations.