The tear film coats the outer surface of the eye and is in direct contact with the environment. It helps provide a smooth surface for refraction of light, provides lubrication to the eye as well as protection against invading pathogens. Tears are essential for a normal healthy ocular surface. Tears have a complex composition, which changes depending on the environment (closed vs open eyes) and stimuli such as watching a sad movie. Understanding the nature of the tear components, where they come from and what they do is important so that we can develop novel ways for treating disorders associated with abnormalities of the tear film. TOSI laboratories have state of the art equipment for analysis of a range of tear film characteristics and we specialize in proteomics and lipidomics. Specific studies currently under way include investigating the nature of tear lipids and how they are changed in dry eye disease and understanding the antimicrobial activity of tears.
The ocular surface is equipped with a very robust system to deal with pathogens and stop them invading and causing infection. However disruption of the ocular surface by trauma (such as wearing a contact lens) or disease opens up the door to infection, which can lead to permanent vision loss. The problem is further exacerbated by a number of pathogens becoming resistant to traditional antimicrobial agents. Research in TOSI laboratories is aimed at understanding the normal ocular defense mechanisms and how they can go wrong or be circumvented by pathogens. With this knowledge we will be better able to boost our own internal defense mechanisms to better defend ourselves against eye infection and develop novel antimicrobial agents to overcome the problem of resistant pathogens.
Specific investigations include understanding the role of antimicrobial peptides such as defensins at the ocular surface, developing antimicrobial peptide based pharmaceuticals and antimicrobial surfaces/devices such as contact lenses. TOSI BSL2 laboratories are fully equipped for in vitro study of several common ocular pathogens (bacteria, fungi, acanthamoeba) for example for solution efficacy testing. We also regularly conduct studies in murine models of bacterial and fungal keratitis.
The ocular surface provides a nice smooth surface for refraction of light and hence clear vision. Any disruption to this smooth surface such as an injury, interferes with refraction and so quality of vision is dramatically reduced. To compensate for this the ocular surface has a robust wound healing response to ensure any injury is rapidly dealt with and smoothed over as effectively as possible. Healing of the outer layer of ocular surface epithelial cells is particularly important as this is a major defensive barrier to infection. Biochemical and molecular studies in the TOSI laboratories use human ocular surface cell and organ culture models as well as a murine model of injury to investigate the roles of various cells and small molecules in the healing process. The knowledge gained from a better understanding of the normal processes is then being applied to develop novel approaches to enhance the wound healing response in situations where it is impaired such as chronic ulcers or diabetes.
Laser refractive surgery is a popular method of vision correction. Here a laser is used to reshape the cornea. While it is often very effective, by its very nature applying the laser creates an injury to the cornea and induces a healing response. Unfortunately in some people the healing response in the corneal stroma is exaggerated leading to several possible complications. We are very interested in studying the cellular and molecular changes that underlie these exaggerated responses with a view to developing ways to control the healing response. The opening of the new Laser Refractive Center (mid 2013) in the Health and Biomedical Sciences Building one floor below TOSI will provide outstanding collaborative opportunities to further our research goal and build on current studies performed in cell culture.
Inflammation is the bodys natural response to any form of insult. It is designed to help clear away damaged cells and tissues, to eradicate any pathogens trying to cause infection and trigger healing. While inflammation is a necessary and important response sometimes it happens when it is not wanted, it happens to excess or it persists too long. In this case inflammation changes from being helpful to harmful. Inflammation causes redness, swelling and pain and in the cornea of the eye is a particular problem as it also interferes with vision. The trick comes in having enough inflammation to get its beneficial effects while stopping too much inflammation and so preventing its harmful effects. This is a very delicate balancing act. Ocular surface inflammation occurs in many situations including allergy, dry eye and infection. Specific studies at TOSI include investigating the role of Toll like receptor mediated inflammation in dry eye and how excessive inflammation contributes to tissue damage during ocular infection.
It is the goal of TOSI and its members to advance the field of ocular surface health by combining scientific mechanisms of disease, clinical tools and research to help with diagnosis, treatment and prevention of ocular surface disease. TOSI has a dedicated research team of support staff, clinicians and scientists capable of full spectrum clinical research capabilities. The TOSI clinical sciences group is capable of performing the full range of ocular surface based clinical research, from population-based cohort studies, to case-control studies to clinical trials. The research team has experience and capabilities to conduct translational clinical studies of any sort, bringing bench side research to the clinic. Further, the research team and facilities are versed in conducting regulatory studies of both devices and therapeutics at any regulatory level, including sponsored Food and Drug Administration (FDA) approval trials of any phase (Phase 1 to Phase 4). Specific capabilities of the TOSI research team and facilities can be found below.
TOSI scientists have established human corneal, conjunctival and meibomian gland cell cultures that can be used to test safety and efficacy of early stage and novel compounds for screening. Comprehensive microbiological evaluation, for example of care solutions, is also available.
The TOSI research group has experience conducting Federal and Industry sponsored clinical research studies of ocular surface health and disease including dry eye disease, meibomian gland disease, contact lenses and complications of lens wear, infection, quality of life, and refractive errors including myopia and presbyopia. TOSI and its affiliated members have experience running epidemiological studies identifying frequency and distribution of disease, in addition to risk factor profile for disease. Further, the TOSI research team has expertise with conducting all phases of clinical trials, including FDA Phase 1 to 4 trials that involve both devices (e.g., artificial tears, rewetting drops, contact lenses and care solutions) and pharmaceuticals. TOSI also has efficient systems in place to work with sponsors on protocol development and Institutional Review Board approval to ensure study start-up happens efficiently. Approved processes and databases are in place to access over 10,000 patient records to implement efficient study recruitment. TOSI has state-of-the art equipment including advanced and custom-built imaging systems designed to accurately and reliably assess tear film and ocular surface structure and function. In summary, TOSI affiliates can design and execute clinical studies to achieve reliable and full-proof results.
TOSI researchers are available for clinical protocol development and consultation given their vast array of expertise and experience working with both industry and regulatory bodies. Further, TOSI works with statisticians versed in both large-scale clinical studies, in addition to clinical trials using the most up-to-date analysis methods to achieve desired result. In this regard, TOSI researchers and staff can help build and design clinical studies that lead to endpoints needed to achieve approvals or to aid in professional marketing.
The TOSI Facilities opened in late 2012 and feature state-of-the art scientific and clinical equipment. TOSI is designed to provide clinical research infrastructure for clinicians to conduct patient-based research of all varieties centered around the ocular surface. TOSI maintains five fully-equiped ophthalmic examination lanes, in addition to individual and private facilities for patient consent, blood draws and survey administration facilitating efficient patient recruitment and flow across its outpatient services. There are dedicated spaces for industry or regulatory monitors to conveniently work with both network and remote wireless access to the internet. Further, for extended study visits, TOSI maintains comfortable spaces for study and for patients to view television programs and access the internet wirelessly. TOSI is capable of conducting translational studies, with compliant and portable chemical fume hoods and biological freezers, allowing for in-office sample collection from patients for chemical or biological endpoint testing.
TOSI maintains an environmentally controlled chamber capable of maintaining humidity levels to less than 10%. The environmental chamber model can be used in studies of devices and drugs associated with dry eye disease, meibomian gland disease or contact lens discomfort. The process facilitates a challenge to the patients ocular and tear system, in very tightly controlled limits, such that disease severity can be induced or made more significant.
There are several state-of-the-art clinical instruments used by TOSI that are valuable in the study of visual optics and imaging of eye structures. For instance, our researchers use the Heidelberg Retina Tomography (HRT) to image different layers of the cornea and identify different cells within the cornea, which makes it a very valuable tool when looking at pathology. The Topcon KR-1W is a multifunctional tool that can evaluate visual acuity by measuring wavefront aberration and corneal topography. In addition, TOSI also has the Marco OPD-III Scan, which allows clinicians to evaluate patients comprehensively, perform refractive and cataract surgery screenings, evaluate postoperative complaints, and determine pathology diagnoses. The group is focused on developing other unique interferometry systems capable of measuring the lipid layer of the tear film, the entire tear film itself in addition to contact lenses in-vivo. The group also has experience with other custom built high resolution microscopy and imaging systems used to assess the tear film and lipid layer.