For example, in our laboratory, we have developed novel in vivo and in vitro methods to study corneal defenses during health, that include new use of imaging technologies to enable us to “see” into living corneas so that we can observe bacteria in action while also monitoring the corneas responses.
Assisting these efforts are new methods in imaging and data analysis 27- 30. 1), and the advent of genomic sequencing of humans 20, of experimental animals 21, and of the microbes that are leading causes of contact lens-associated infection 22, combined with the recent development of new, highly sensitive, and readily available screening tools that can identify key molecules involved in critical biological processes (for example, those critical for defense, and those impacted during susceptibility) 23- 26. This has come about through the development of rodent contact lenses 18, 19 ( Fig. While these hurdles have prevented researchers from directly addressing key questions surrounding the pathogenesis of contact lens-related keratitis for almost three decades, we have recently entered a new era of discovery that could soon lead to the eradication of contact lens-related infections. The hit and miss nature of research in this field has, in turn, made it difficult for investigators to obtain funding for basic biological research aimed at addressing pathogenesis of contact lens-related complications, further delaying progress. rabbits) poses similar problems, and is also prohibitively expensive for generating sufficient data for statistical analysis. Use of human lenses on larger animals, (e.g. The major obstacle interfering with the development of a good contact lens infection model has been a lack of availability of contact lenses that properly fit the eyes of small animals.
When attempting to do such experiments in vivo one finds that bacteria do not interact at all with the epithelium of healthy corneas, leaving no pathology to study 17. To study how bacteria interact with the corneal epithelium, we and others have used corneal epithelial cells grown in vitro. However, these models bypass the corneal epithelium, and are not suited to studying circumstances that surround the actual initiation of contact lens-related infection, or exploring why the cornea is resistant to infection when it is healthy. These models have been of great value in discerning the inflammatory and immune responses involved in disease and its resolution once an infection is already underway 8, 12, 15, 16. Until recently, in vivo rodent models available to researchers studying corneal infection were limited to one that requires the cornea to be scratch-injured to expose the stroma, and another in which bacteria are injected into the stroma. Sometimes associated “markers” have been examined that later turned out to have little to do with the mechanism being studied.Ī second obstacle to progress in this field has been the lack of suitable animal models.
Researchers in the field have therefore resorted to making educated guesses as to what molecules, processes or cells to focus on. A contributor to this problem has been our sketchy understanding of the normal biochemistry and cell biology of the ocular surface, combined with a lack of tools for sorting out which of the many factors present at the ocular surface were critical to defense against infection. Naturally, it is difficult to draw conclusions about how lens wear might impact defenses that have not yet been defined. The first is the lack of basic knowledge about how the healthy ocular surface normally defends itself against infection. Two major stumbling blocks have hindered progress in this field. 1- 7 For more than 20 years, we and others in this field, have worked towards understanding why the corneas of contact lens wearers are more susceptible to infection. Contact lens wear continues to be a significant risk factor for the development of acute sight-threatening corneal infections (microbial keratitis).
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