Alpha-melanocyte-stimulating hormone (α-MSH) and its binding receptors (the melanocortin receptors) play important roles in maintaining ocular tissue integrity and immune homeostasis. Particularly extensive studies have demonstrated the biological functions of α-MSH in both immunoregulation and cyto-protection. This review summarizes the current knowledge of both the physiological and pathological roles of α-MSH and its receptors in the eye. We focus on recent developments in the biology of α-MSH and the relevant clinical implications in treating ocular diseases.

Highly inflamed and neovascularized corneal graft beds are known as high-risk (HR) environments for transplant survival. One of the primary factors leading to this rejection is reduction in the suppressive function of regulatory T cells (Treg). Our results show that myeloid-derived suppressor cells (MDSC) counteract interleukin-6-mediated Treg dysfunction by expressing interleukin-10. Additionally, MDSC maintain forkhead box P3 stability and their ability to suppress IFN-γ⁺ Th1 cells. Administering MDSC to HR corneal transplant recipients demonstrates prolonged graft survival via promotion of Treg while concurrently suppressing IFN-γ⁺ Th1 cells. Moreover, MDSC-mediated donor-specific immune tolerance leads to long-term corneal graft survival as evidenced by the higher survival rate or delayed survival of a second-party C57BL/7 (B6) graft compared to those of third-party C3H grafts observed in contralateral low-risk or HR corneal transplantation of BALB/c recipient mice, respectively. Our study provides compelling preliminary evidence demonstrating the effectiveness of MDSC in preventing Treg dysfunction, significantly improving graft survival in HR corneal transplantation, and showing promising potential for immune tolerance induction.

Corneal transplantation is the most common form of solid tissue grafting, with an approximately 80% to 90% success rate. However, success rates may decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathologic processes that cause graft rejection, we used streptozotocin-induced type 1 DM (DM1) and transgenic Lep^ob/ob type 2 DM (DM2) diabetic murine models as donors and nondiabetic BALB/c as recipients. DM resulted in an increased frequency of corneal antigen-presenting cells (APCs) with an acquired immunostimulatory phenotype. Following transplantation, recipients that received either type of diabetic graft showed increased APC migration and T helper type 1 alloreactive cells, impaired functional regulatory T cells, and graft survival. Insulin treatment in streptozotocin-induced diabetic mice led to an increased tolerogenic profile of graft APC, lower T helper type 1 sensitization, and a higher frequency of functional regulatory T cells with high suppressive capacity, reflected in increased graft survival. We conclude that both DM1 and DM2 in donors can impact corneal APC functional phenotype, rendering the tissue more immunogenic and thereby increasing the risk of graft failure.

Corrigendum: Therapeutic potential of topical administration of acriflavine against hypoxia-inducible factors for corneal fibrosis

Cellular senescence is characterized by stable cell-cycle arrest and a senescence-associated secretory phenotype (SASP). Recurrent desiccating, oxidative, ultraviolet, microbial, and immune-mediated insults may induce stress-induced premature senescence (SIPS) in ocular surface tissues. PubMed and Web of Science were searched from database inception to 30 June 2026. Primary human, animal, and in vitro studies were prioritized, and direct evidence of senescence was distinguished from indirect stress-related or SASP-like associations. The p53–p21^CIP1–pRB and p16^INK4a–pRB pathways mediate senescence-associated cell-cycle arrest. Reactive oxygen species (ROS)–p38 mitogen-activated protein kinase (p38 MAPK) and cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) signaling act as stress-sensing and inflammatory pathways, whereas mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) contribute to SASP and metabolic regulation. Transient senescence may support wound repair and immune clearance, whereas persistent senescence may contribute to epithelial and endothelial dysfunction, tear-film instability, immune dysregulation, fibrosis, and extracellular matrix remodeling. Mechanistic support is strongest in selected experimental models; evidence in several human ocular surface disorders remains associative. Cellular senescence is a context-dependent contributor to ocular surface pathology. Senolytic and senomorphic strategies remain predominantly preclinical and require disease-, cell-, and stage-specific validation.