Corneal endothelial dystrophy is a progressive disease with gradual loss of vision and characterized by degeneration and dysfunction of corneal endothelial cells. Mutations in SLC4A11, a Na+ dependent OH− transporter, cause congenital hereditary endothelial dystrophy (CHED) and Fuchs’ endothelial corneal dystrophy (FECD), the two most common forms of endothelial degeneration. Along with genetic factors, oxidative stress plays a role in pathogenesis of several corneal diseases. In this study we looked into the role of SLC4A11 in antioxidant stress response in human corneal endothelial cells (HCEnC). We found increased expression of SLC4A11 in presence of oxidative stress. Depletion of SLC4A11 using targeted siRNA, caused an increase in reactive oxygen species, cytochrome c, lowered mitochondrial membrane potential, and reduced cell viability during oxidative stress. Moreover, SLC4A11 was found to be necessary for NRF2 mediated antioxidant gene expression in HCEnC. On the other hand, over expression of SLC4A11 reduces reactive oxygen species levels and increases cell viability. Lastly, CHED tissue specimens show evidence of oxidative stress and reduced expression of NRF2. In conclusion, our data suggests a possible role of SLC4A11 in regulating oxidative stress, and might be responsible for both the etiology and treatment of corneal endothelial dystrophy.

Pseudomonas aeruginosa is an opportunistic pathogen and is the major cause of corneal infection worldwide that secret several virulent toxins through its type III secretion system (T3SS). In defense against pathogenic insults, epithelial cells and macrophages express antimicrobial peptides (AMPs) that are essential components of host immune response. In this study, we have determined the expression of several AMPs in patients with P. aeruginosa corneal infection. We also used an in vitro model of infection using human corneal epithelial cells and macrophages to determine the gene expression of AMPs and cellular response to wild-type and T3SS mutant P. aeruginosa. We found differential expression of several AMPs in patient samples and also found that P. aeruginosa repress AMP expression in both epithelial cells and macrophages by its T3SS in vitro. It dampens AMP expression by causing delay in NF-κB, p38 and ERK activation and inhibits reactive oxygen species generation in these cells by its T3SS. Our study show the profile of AMPs expressed during P. aeruginosa keratitis and suggest the pivotal role of the T3SS in epithelial cells and macrophages during P. aeruginosa infection.

| Cornea being constantly exposed to sunlight and atmospheric oxygen is readily prone to oxidative damages. The functional antioxidant signaling helps maintain the levels of reactive oxygen species in the cells and keeps the cornea healthy. Corneal endothelial dystrophies include a group of corneal diseases that are marked by progressive degeneration of corneal endothelium leading to loss of vision. The increased level of oxidative stress in several corneal endothelial dystrophies indicates that there might be disruption in proper functioning of these signaling pathways. Various strategies to improve antioxidant signaling pathways may help develop novel clinical interventions to combat degeneration of endothelial cells that leads to vision loss. This review gives an overview of oxidative stress in the pathogenesis of corneal diseases.

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