The health of the cornea has always been of great concern in the field of ophthalmology. The cornea is a transparent fibrous membrane at the forefront of the eyeball with barrier and refractive functions (Fig. 1) (Meek and Knupp, 2015; Mohan et al., 2022b). It is susceptible to both external insults such as chemical injuries and pathogen infections and systemic disorders such as Sjögren's syndrome (SS), graft-versus-host disease (GVHD) and diabetes which induce acquired corneal diseases (Baradaran-Rafii et al., 2017; Di Zazzo et al., 2021; Durand et al., 2021; Hakim and Farooq, 2022; Nair et al., 2021). Severely acquired corneal diseases associated with various pathological changes, such as opacity, scars, neovascularization and fibrosis, can exert enormous impacts on vision and even lead to blindness, affecting many people and imposing burdens on both individuals and societies (Chen et al., 2023; Rocha-de-Lossada et al., 2021; Segars and Trinkaus-Randall, 2023; Su et al., 2020; Wang et al., 2023; Yang et al., 2023). Although encouraging progress has been made, we still face numerous difficulties and obstacles in curing corneal lesions. Although new approaches such tear proteomics and metagenomics have been developed to achieve precise diagnosis and treatment of corneal infections, topical broad-spectrum antibiotics are still the most widely used treatment clinically, and pathogen resistance is a lingering problem (Cabrera-Aguas et al., 2022; Kuo et al., 2019; Parekh et al., 2020). Corticosteroids are effective for controlling corneal inflammation but elevated intraocular pressure and systemic side effects must be monitored closely (Dang et al., 2022). Once severe perforation and opacity occur, corneal transplantation is the last resort, which is still accompanied by immune rejection and donor shortages (Hos et al., 2019). Therefore, it is imperative to determine new approaches for the treatment of acquired corneal injuries.

The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway extensively regulates a wide range of metabolic and immune inflammatory responses and is crucial in the pathogenic mechanisms of many diseases (Nakao et al., 2020; Philips et al., 2022). Therapeutic interventions that target components of JAK/STAT3 signaling have shown great efficacy in oncology, cardiology, hematology and osteoarticular diseases (Bharadwaj et al., 2020; Dufva et al., 2018; Hu et al., 2022; Mohan et al., 2022a; Nakao et al., 2020).

Notably, accumulating evidence has identified JAK/STAT3 dysregulation in many acquired corneal diseases, such as dry eye diseases (DED), infectious keratitis, corneal alkali burns, diabetic keratopathy (DK) and corneal graft rejection (CGR) (Cao et al., 2021; Di Zazzo et al., 2021; Gurzov et al., 2016; Han et al., 2020; Qu et al., 2019; Yu et al., 2021). Due to space limitations, our review will primarily focus on the first three disorders mentioned. We will delve into the multiple roles JAK/STAT3 signaling plays in the occurrence and progression of these common acquired corneal disorders to identify potential therapeutic targets for future clinical applications.