Toward an Animal Model of the Human Tear Film: Biochemical Comparison of the Mouse, Canine, Rabbit, and Human Meibomian Lipidomes

Butovich, Igor A.; Lu, Hua; McMahon, Anne; Eule, Johanna Corinna

doi:10.1167/iovs.12-10516

Cited by 80 publications

(131 citation statements)

References 41 publications

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“…The results of the HPLC-MS and other analyses of these normal samples already have been reported recently. 25,26 The analyses demonstrated a low intersample variability of the meibomian lipids among healthy, non-dry eye subjects. The lipid composition of meibum samples analyzed in our current study was shown to match the average lipid composition of meibum reported previously.…”

Section: Collection Of Meibum Samplesmentioning

confidence: 87%

“…The lipid composition of meibum samples analyzed in our current study was shown to match the average lipid composition of meibum reported previously. 17,[24][25][26][27][28] The biophysical experiments with fresh samples were conducted within a few days of collection. Bovine brain Cer and FC (>99% pure) were purchased from Sigma-Aldrich Corp.…”

Section: Collection Of Meibum Samplesmentioning

confidence: 99%

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Disruption and Destabilization of Meibomian Lipid Films Caused by Increasing Amounts of Ceramides and Cholesterol

Arciniega¹,

Uchiyama²,

Butovich

2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We evaluated quantitatively direct effects of ceramide (Cer) and free cholesterol (FC) on meibomian lipid films (MLF) using a Langmuir trough (LT) and a Brewster angle microscope (BAM). METHODS. Meibum was obtained from healthy volunteers. A series of mixtures of meibum with Cer or FC (mixed MLF)taken in different ratios were tested. Standard rheologic parameters, such as elasticity and hysteresis of MLF, were computed. BAM was used to study the morphology of MLF.RESULTS. Pure MLF were capable of withstanding multiple compression-expansion cycles with little hysteresis observed (~1.9 J/g meibum). The films made of either pure Cer or pure FC were clearly collapsible, and had much higher rigidity and hysteresis than pure meibum. Adding progressively higher amounts of Cer or FC to meibum had a strong impact on the rigidity, stability, and morphology of the mixed MLF: their hysteresis increased many fold compared to pure meibum. A concomitant increase in the rigidity and collapsibility of the mixed MLF was observed.CONCLUSIONS. Cer and FC changed the surface properties of mixed MLF in a way that implied their destabilization and/or disruption. One of the mechanisms that might lead to these effects is strong aggregation of meibum lipids with FC or Cer that leads to the formation of smaller particles of meibum surrounded by a thinner layer of FC or Cer. As Cer and FC can be elevated in meibum and the tear film because of certain pathologic processes, or can be of exogenous nature, our results can explain (partially) a less stable tear film in those subjects. (Invest Ophthalmol Vis Sci. 2013;54:1352-1360) DOI:10.1167/iovs.12-10662 T he preocular tear film (TF) is a complex aqueous structure that is enriched with lipids, proteins, carbohydrates and other molecules of biological origin. TF covers the entire ocular surface.1 The outermost layer of the tear film, also called tear film lipid layer (TFLL), is formed predominantly from a mixture of lipids called ''meibum.'' Meibum is produced by holocrine lipid-secreting meibomian glands (MG), which are located in the tarsal plates of the eyelids. [2][3][4] This outer layer is believed to prevent the evaporation of the TF, lubricate the ocular surface, and avert the invasion of pathogenic microorganisms. 5 Reportedly, adverse changes in the lipid composition of meibum 6-12 could impact negatively the integrity and stability of the TF, compromising the health of the ocular surface, and predisposing it to the development of various ocular pathologies. One of the latter, the dry eye disease (DED), is one of the most prevalent ocular diseases. One of the forms of DED is known commonly as meibomian gland dysfunction (MGD), 13 while another common condition that is associated with meibum and TFLL abnormalities is chronic posterior blepharitis (CPB). 14 Comprehensive chemical analyses of normal (i.e., non-dry eye) meibum samples collected from healthy subjects have demonstrated a very complex nature of meibomian lipids. Many lipid classes were shown to be present in normal ...

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Section: Collection Of Meibum Samplesmentioning

confidence: 87%

Section: Collection Of Meibum Samplesmentioning

confidence: 99%

Disruption and Destabilization of Meibomian Lipid Films Caused by Increasing Amounts of Ceramides and Cholesterol

Arciniega¹,

Uchiyama²,

Butovich

2013

Invest. Ophthalmol. Vis. Sci.

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“…It is worthwhile noting that to analyse the lipids in meibum and in tears (see below) is extraordinarily difficult because of small sample sizes, ease of contamination, biological variation, major differences in lipid classes (each class needs different separation and analysis techniques), lack of standards, and the plethora of individual lipid species within a single sample (something only truly appreciated by those attempting the analysis). Overlayed on this complexity has been a confusion generated because on some occasions contaminants from plastics or solvents have been attributed to meibum (Butovich, 2009a;Nichols et al, 2007), and because the composition of rabbit meibum (used as an animal model) appears to be markedly different from that of other animals including humans (Butovich et al, 2012). It is therefore unsurprising that the analysis of the lipids has been a topsy-turvy ride with considerable variation in the data.…”

Section: Composition Of Meibummentioning

confidence: 99%

The real reason for having a meibomian lipid layer covering the outer surface of the tear film – A review

Millar

Schuett

2015

Experimental Eye Research

111

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“…Owing to anatomical similarities, mice are a popular model for studying the pathogenesis of MGD. Furthermore, mouse meibum lipid composition strongly resembles that of humans (Butovich et al, 2012) and mouse Meibomian glands show an age-related atrophy that mimics changes seen in age-related MGD (Jester et al, 2011). MGD has been studied in mice exposed to a desiccating environment (Suhalim et al, 2014) or in diverse genetically modified mice lacking enzymes or transcription factors important for sebaceous lipid synthesis (House et al, 2010;McMahon et al, 2014;Yagyu et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis, and ocular integrity in mice

Dahlhoff¹,

Camera

Schäfer

et al. 2016

Development

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Sebocytes, which are characterized by lipid accumulation that leads to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools that allow targeting of sebocytes while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, which is expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of Cre recombinase. Both RT-PCR analysis and crossing into Rosa26-lacZ reporter mice and Kras G12D mice confirmed Cre activity specifically in SGs, with no activity in other skin compartments. Importantly, loss of SCD3 function did not cause detectable phenotypical alterations, endorsing the usefulness of Scd3-Cre mice for further functional studies. Scd3-Cre-induced, diphtheria chain A toxin-mediated depletion of sebaceous lipids resulted in impaired water repulsion and thermoregulation, increased rates of UVB-induced epidermal apoptosis and caused a severe pathology of the ocular surface resembling Meibomian gland dysfunction. This novel mouse line will be useful for further investigating the roles of sebaceous lipids in skin and eye integrity.

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Toward an Animal Model of the Human Tear Film: Biochemical Comparison of the Mouse, Canine, Rabbit, and Human Meibomian Lipidomes

Abstract: Our side by side comparison of the rabbit and the human meibum demonstrated their vast differences. Thus, the rabbit seems to be a poor animal model of the human tear film, at least when studying its biochemistry and biophysics.

Cited by 80 publications

References 41 publications

Disruption and Destabilization of Meibomian Lipid Films Caused by Increasing Amounts of Ceramides and Cholesterol

Disruption and Destabilization of Meibomian Lipid Films Caused by Increasing Amounts of Ceramides and Cholesterol

The real reason for having a meibomian lipid layer covering the outer surface of the tear film – A review

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis, and ocular integrity in mice

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