No abstract

Currently, over 10 million people worldwide are affected by corneal blindness. Corneal trauma and disease can cause irreversible distortions to the normal structure and physiology of the cornea often leading to corneal transplantation. However, donors are in short supply and risk of rejection is an ever-present concern. Although significant progress has been made in recent years, the wound healing cascade remains complex and not fully understood. Tissue engineering and regenerative medicine are currently at the apex of investigation in the pursuit of novel corneal therapeutics. This review uniquely integrates the clinical and cellular aspects of both corneal trauma and disease and provides a comprehensive view of the most recent findings and potential therapeutics aimed at restoring corneal homeostasis.

The purpose of this study was to investigate the protective role of peroxisome proliferator–activated receptor α (PPARα) against diabetic keratopathy and corneal neuropathy. Corneal samples were obtained from human donors with and without diabetes. Streptozotocin-induced diabetic rats and mice were orally treated with PPARα agonist fenofibrate. As shown by immunohistochemistry and Western blotting, PPARα was downregulated in the corneas of humans with diabetes and diabetic rats. Immunostaining of β-III tubulin demonstrated that corneal nerve fiber metrics were decreased significantly in diabetic rats and mice, which were partially prevented by fenofibrate treatment. As evaluated using a Cochet-Bonnet aesthesiometer, corneal sensitivity was significantly decreased in diabetic mice, which was prevented by fenofibrate. PPARα−/− mice displayed progressive decreases in the corneal nerve fiber density. Consistently, corneal sensitivity was decreased in PPARα−/− mice relative to wild-type mice by 21 months of age. Diabetic mice showed increased incidence of spontaneous corneal epithelial lesion, which was prevented by fenofibrate while exacerbated by PPARα knockout. Western blot analysis revealed significantly altered neurotrophic factor levels in diabetic rat corneas, which were partially restored by fenofibrate treatment. These results indicate that PPARα protects the corneal nerve from degeneration induced by diabetes, and PPARα agonists have therapeutic potential in the treatment of diabetic keratopathy.

Primary open‐angle glaucoma (POAG) is characterized by irreversible neurodegeneration accompanied by visual field defects and high intraocular pressure. Currently, an effective treatment is not available to prevent the progression of POAG, other than treatments to decrease the high intraocular pressure. We performed proteomic analysis of aqueous humour (AH) samples from patients with POAG combined with cataract and patients with cataract to obtain a better understanding of the pathogenesis of POAG and explore potential treatment targets for this condition. Samples were collected from 10 patients with POAG combined with cataract and 10 patients with cataract. Samples from each group were pooled. A high‐resolution, label‐free, liquid chromatography‐tandem mass spectrometry‐based quantitative proteomic analysis was performed. In total, 610 proteins were identified in human AH samples from the two groups. A total of 48 up‐regulated proteins and 49 down‐regulated proteins were identified in the POAG combined with cataract group compared with the control group. Gene Ontology (GO) analysis revealed key roles for these proteins in inflammation, immune responses, growth and development, cellular movement and vesicle‐mediated transport in the biological process category. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the down‐regulated expression of glutathione S‐transferase P (GSTP1) in the glutathione metabolism signalling pathway in the POAG combined with cataract group. Additionally, certain significantly differentially expressed proteins in the proteomic profile were verified by enzyme‐linked immunosorbent assay (ELISA). GSTP1 levels were reduced in the human AH samples from the POAG combined with cataract group, based on the results of ELISA and proteomic profiling. Therefore, GSTP1, a redox‐related marker, may be involved in the pathological process of POAG and may become a treatment target in the future.

Keratoconus (KC) and chronic diabetes mellitus (DM) are both associated with significant defects in the human corneal structure. Studies have long suggested that DM is linked to KC, mainly via the crosslinking mechanism, but scientific evidences are lacking. The role of altered systemic metabolism is well-established in both DM and KC with studies suggesting localized altered cellular metabolism leading to the development of corneal pathologies. We have previously characterized the metabolic defects associated with both conditions using targeted metabolomics. To compare metabolic differences between KC and DM-derived corneal fibroblasts, we performed a respective study of two cohorts of the KC and DM populations using a retrospective analysis of targeted metabolomics data. The goal of this study was to identify the group of differentially regulated metabolites, in KC versus DM, so that we may unravel the link between the two devastating corneal pathologies.