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Bacterial Interactions with the Ocular Surface
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Bacterial Interactions with the Ocular Surface. |
| 개인저자 | Wan, Stephanie J. |
| 단체저자명 | University of California, Berkeley. Vision Science. |
| 발행사항 | [S.l.]: University of California, Berkeley., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 143 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781085794053 |
| 학위논문주기 | Thesis (Ph.D.)--University of California, Berkeley, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Fleiszig, Suzanne M. J. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Bacterial keratitis is a devastating, sight-threatening infection of the cornea. However, in order to truly grasp how bacterial keratitis ensues, it is first imperative to understand how the healthy eye is maintained. Only then can we truly decipher the intricacies of how a cornea becomes susceptible to potentially dangerous microorganisms.Bacteria surround us and inhabit almost every niche in our environment and on our bodies. Thus, the question arose: are bacteria present on the ocular surface, and if so, what role do they play in maintaining health? This is the first question I sought to address in my dissertation. I used bacterial labeling techniques to be able to identify live microbes and gain a spatial understanding of the bacteria on the mouse ocular surface. Interestingly, I found that live bacteria are rarely present on the cornea. This was in stark contrast to the conjunctiva, which does host bacterial inhabitants, including long filamentous bacteria. The cornea's ability to prevent a microbiome is dependent on IL-1R and MyD88 signaling, an important finding to demonstrate the role of this pathway during homeostasis and not just as a response to pathogens.It is fortunate that the cornea is an expert at preventing bacterial colonization considering that it is constantly exposed to the environment and all of the surrounding microbes. Thus, I wanted to gain a further understanding of how the cornea prevents a microbiome on its surface. Tear fluid has previously been shown to be an important factor towards bacterial defense of the ocular surface. Several constituents that make up basal tears are antimicrobial and impede bacterial virulence. One such component is DMBT1, a glycoprotein that inhibits bacterial twitching. Twitching motility is a surface movement important for epithelial traversal and virulence. How DMBT1 inhibits Pseudomonas aeruginosa twitching, a common cause of contact lens related corneal infections, was investigated. It was found that N-glycosylation of DMBT1 contributes to this defense mechanism.The cornea is the most innervated tissue in the body. Not only are nerves important for sensory transduction, but they also can have immunomodulatory roles. The contributions of sensory nerves in regard to corneal defense has previously not been explored. Thus, I sought to unravel the role of polymodal nociceptors, TRPA1 and TRPV1, in corneal defense against bacteria. I found that these neuronally expressed ion channels contribute to preventing bacterial colonization on the cornea and communicate with immune cells when the healthy cornea is challenged with P. aeruginosa.After exploring several factors involved in keeping the cornea free of bacteria, I next wanted to gain a better understanding of how common ocular modulations affect its ability to withstand bacteria. First, I explored the impact of dry eye disease, a common debilitating disease with an unknown pathogenesis, on susceptibility to bacterial adhesion. Dry eye disease is associated with a myriad of factors that hinder corneal defense such as altered tear film composition, reduction of antimicrobial peptides, and poor epithelial integrity. I used an experimentally induced mouse model of dry eye disease and determined if environmental bacteria could colonize the corneas. Interestingly, I found that dry eye disease did not increase susceptibility to bacterial colonization on the cornea and no changes occurred on the conjunctiva. Thus, local bacteria on the ocular surface are unlikely to play a role in the pathogenesis of dry eye disease and induction of the disease does not hamper the ability of the cornea to ward off unwanted inhabitants.Finally, the effects of contact lens wear on the cornea was studied. Progress to decipher how a contact lens alters the corneal environment and any implications this may have, has previously been hindered by limitations of human studies and a lack of animal models. Our lab developed a silicon-hydrogel contact lens to fit on mice that mimics a human lens wearer. We found that a contact lens on a healthy cornea initiates a parainflammatory response observed as an infiltration of dendritic cells at 24 h after lens wear and an influx of neutrophils after 5 days of lens wear. Interestingly, this increase in immune cells in the cornea did not disrupt the macroscopic morphology and the cornea remained clear. Colonization of environmental bacteria on the contact lens was also detected. This understanding of how the lens affects the healthy cornea is imperative to grasp what is being altered that increases susceptibility to bacterial keratitis.Overall, this dissertation focuses on bacterial interactions with the ocular surface. First, I determined that the cornea does not host a microbiome. Several factors contribute to keeping the cornea free of bacteria including tear fluid, and glycoprotein DMBT1, IL-1R and MyD88 dependent signaling, and polymodal nociceptors. Dry eye disease does not increase the susceptibility to bacterial colonization but contact lens wear is associated with bacterial adhesion. Whether these bacteria on the lens contribute to the infiltration of immune cells observed with lens wear remains to be understood. The results from this dissertation increases our general understanding of how the ocular surface maintains health and prevents bacterial colonization. Studies also give insights into mechanisms impacted by lens wear that may contribute to the increased risk of bacterial keratitis. |
| 일반주제명 | Microbiology. Immunology. Medicine. |
| 언어 | 영어 |
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