Antimicrobial Role of Human Meibomian Lipids at the Ocular Surface

Mudgil, Poonam

doi:10.1167/iovs.14-15512

Cited by 55 publications

(36 citation statements)

References 44 publications

(42 reference statements)

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“…Meibum is considered an important part of the tear film/tear film lipid layer (TF/TFLL) defense system that protects eyes from microorganisms and desiccation [6–10]. TF/TFLL combination also serves as a lubricant [11] that smoothes movements of the eyeball and the eyelids, and improves visual acuity [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Dissecting lipid metabolism in meibomian glands of humans and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues

Butovich

McMahon

Wojtowicz

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

118

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Lipids comprise the bulk of the Meibomian gland secretion (meibum) which is produced by meibocytes. Complex arrays of lipogenic reactions in Meibomian glands, which we collectively call meibogenesis, have not been explored on molecular level yet. Our goals were to elucidate the possible biosynthetic pathways that underlie generation of meibum, reveal similarities in, and differences between, lipid metabolism in Meibomian glands and other organs and tissues, and integrate Meibomian gland studies into the field of general metabolomics. Specifically, we have conducted detailed analyses of human and mouse specimens using genomic, immunohistochemical, and lipidomic approaches. Among equally highly expressed genes found in Meibomian glands of both species were those related to fatty acid elongation, branching, desaturation, esterification, reduction of fatty acids to alcohols, and cholesterol biosynthesis. Importantly, corresponding lipid products were detected in meibum of both species using lipidomic approaches. For the first time, a cohesive, unifying biosynthetic scheme that connects genomic, lipidomic, and immunohistochemical observations is outlined and discussed.

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Section: Introductionmentioning

confidence: 99%

Dissecting lipid metabolism in meibomian glands of humans and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues

Butovich

McMahon

Wojtowicz

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

118

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“…Additional lipid classes are triglycerides, sphingosine and ceramides, as well as cholesteryl esters [45] . While a lubricant function has been primarily attributed to tear lipids, a recent study suggested growth inhibitory activity of whole tear lipid extracts against several Gram-positive and Gramnegative bacteria [46] .…”

Section: Meibummentioning

confidence: 99%

“…More recent studies describe rapid membrane depolarization in S. aureus treated with palmitoleate as well as when treated with glycerol ethers, sphingosine, and acyl-amines [60] . As demonstrated by scanning electron microscopy, meibomian lipids from tears cause major structural damage including distortion, loss or regular cell shape, and cell lysis in S. aureus, P. aeruginosa, and Serratia marcescens [46] . The more pronounced antimicrobial activity of unsaturated FFA compared to their saturated counterparts [61] may be at least in part attributed to lipid peroxidation.…”

Section: Mechanisms Of Antimicrobial Actionmentioning

confidence: 99%

Antimicrobial lipids: Emerging effector molecules of innate host defense

Porter

Daniel²,

Alvarez³

et al. 2015

WJI

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The antimicrobial properties of host-derived derived lipids have become increasingly recognized and evidence is mounting that antimicrobial lipids (AMLs), like antimicrobial peptides, are effector molecules of the innate immune system and are regulated by its conserved pathways. This review, with primary focus on the human body, provides some background on the biochemistry of lipids, summarizes their biological functions, expands on their antimicrobial properties and site-specific composition, presents modes of synergism with antimicrobial peptides, and highlights the more recent reports on the regulation of AML production as well as bacterial resistance mechanisms. Based on extant data a concept of innate epithelial defense is proposed where epithelial cells, in response to microbial products and proinflammatory cytokines and through activation of conserved innate signaling pathways, increase their lipid uptake and up-regulate transcription of enzymes involved in antimicrobial lipid biosynthesis, and induce transcription of antimicrobial peptides as well as cytokines and chemokines. The subsequently secreted antimicrobial peptides and lipids then attack and eliminate the invader, assisted by or in synergism with other antimicrobial molecules delivered by other defense cells that have been recruited to the site of infection, in most of the cases. This review invites

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“…It has also been associated with the increased chemotaxis of neutrophils and other immune cells during the prolonged period of eyelid closure during sleep 27. Tear lipids can also augment the bactericidal properties of tears, as short‐chain lipids affect the surface properties of the bacterial cell membrane, and long‐chain lipids have a direct effect on bacterial metabolism 20,28. It has been shown that tear film lipids can induce cell lysis, distortion, and cell wall damage in both Gram‐negative and Gram‐positive bacteria 28.…”

Section: Introduction: the Barriers To Topical Ocular Drug Deliverymentioning

confidence: 99%

“…Tear lipids can also augment the bactericidal properties of tears, as short‐chain lipids affect the surface properties of the bacterial cell membrane, and long‐chain lipids have a direct effect on bacterial metabolism 20,28. It has been shown that tear film lipids can induce cell lysis, distortion, and cell wall damage in both Gram‐negative and Gram‐positive bacteria 28. These processes all act as part of a wider complex mechanism of ocular surface protection.…”

Section: Introduction: the Barriers To Topical Ocular Drug Deliverymentioning

confidence: 99%

Material, Immunological, and Practical Perspectives on Eye Drop Formulation

Bennett

Chinnery

Downie

et al. 2020

Adv Funct Materials

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Eye drops are the most common and inexpensive approach to topical ocular drug delivery. Eye drops offer a noninvasive treatment strategy; however, this can be detrimental to therapeutic efficacy when compared to invasive methods such as surgeries, implants, and injections. Improvements to the efficacy of the topical delivery of drugs to ocular tissues are currently being explored and much of this work centers on adjusting the formulation of the eye drops and prolonging the bioavailability of the therapeutic agent. This is often in preference to improving other patient‐focused or clinical factors. In this progress report, conventional, commercially available polymer eye drops are explored and the ability for current and future innovations to maintain the existing benefits of eye drops to the patient is assessed. The final materials and form of the drops (liquid, gel, or other) and the immunological implications for the user are explored. There is currently no consensus for how to most effectively improve the ocular retention and drug delivery capabilities of eye drops, but key issues are highlighted in the context of current methods under development, and potential questions and considerations for future innovations are raised.

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Antimicrobial Role of Human Meibomian Lipids at the Ocular Surface

Cited by 55 publications

References 44 publications

Dissecting lipid metabolism in meibomian glands of humans and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues

Dissecting lipid metabolism in meibomian glands of humans and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues

Antimicrobial lipids: Emerging effector molecules of innate host defense

Material, Immunological, and Practical Perspectives on Eye Drop Formulation

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