Infectious keratitis is a corneal disease that usually develops quickly and if left untreated can cause partial or full blindness. Corneal opacities, which are largely caused by infectious keratitis are the 4th leading cause of blindness globally. Current epidemiological data suggest that there are over 2 million new cases of infectious keratitis per year worldwide. Etiological and epidemiological patterns vary between developed and developing countries. Trauma is often the most significant risk factor for developing countries, reflecting the increased size of agriculture in these countries whereas in developed countries, infectious keratitis is usually associated with contact lens wear. These factors compromise the resistance mechanisms of the cornea rendering it susceptible to infection. Infectious keratitis can be caused by bacteria, fungi, viruses and parasites. Standard treatment involves the use of topical or systemic antibiotics, but the ophthalmologists are often faced by a diagnostic and treatment dilemma as to whether it is a bacterial or fungal infection or mixed? In addition to this, is an expensive treatment and the visual outcome is often poor. To make matters worse, the increasing emergence of multi-drug resistance is another major challenge. Taking into account the potentially visually threatening consequences and limited treatment strategies, in recent years, alternative therapies have been considered in severe, progressive cases.
Corneal collagen crosslinking (CXL) procedures have been proposed as a novel treatment strategy for the management of progressive, unresponsive infectious keratitis. The initial treatment was known as photo-activated chromophore corneal collagen crosslinking (PACK-CXL), which consisted of riboflavin irradiated with ultraviolet A (UVA) light.
In the last decade, the use of genipin, a natural crosslinking agent derived from the plant Gardenia jasminoides, to crosslink the cornea was demonstrated by Dr Avila who proposed that genipin can exert a corneal stiffening effect similar to riboflavin UVA, without the need for radiation. Following some in vivo studies they also demonstrated that genipin exerts minimal toxicity to the corneal endothelial cells.
Owing to its excellent biocompatibility and low toxicity properties, genipin has established a captivating potential in different research areas including biomedicine and bioengineering and several studies have shown that it exhibits several key pharmacological properties, including anti-inflammatory, antioxidant, and anti-metastatic activities. The quest to develop new antimicrobial therapies, the promising data supporting that corneal crosslinking could kill bacteria irrespective of their antibiotic resistance, and importantly the therapeutic potential of genipin led us to formulate the hypothesis that genipin crosslinking could be used for the treatment of infectious keratitis. The overarching aim of this project was therefore to investigate the antimicrobial properties of genipin in an ex vivo model of corneal infectious keratitis.
