The role of sphingolipids in meibomian gland dysfunction and ocular surface inflammation

Paranjpe, Vikram; Grambergs, Richard C.; Mandal, Nawajes A.

doi:10.1016/j.jtos.2022.07.006

Cited by 10 publications

(5 citation statements)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the inflammatory pathology as the key to any vesicating injury suggests their integral association with lipid signaling. Bioactive lipids such as eicosanoids, sphingolipids, specialized pro-resolving mediators (SPM), and endocannabinoids are classic cellular and tissue mediators that are involved not only in initiating and potentiating inflammation but also in the ultimate cessation or resolution of the inflammatory responses [36,[48][49][50]. With our eventual goal of understanding lipid signaling in the pathological mechanisms of vesicating injuries, in this maiden step, we determined the association of sphingolipids in an acute stage of NM-exposed mice eyes (3 DPI).…”

Section: Discussionmentioning

confidence: 99%

“…Cer can be the precursor for other bioactive sphingolipids such as sphingosine, S1P, and C1P. They regulate apoptosis, cell growth, inflammation, angiogenesis, intracellular trafficking, and other processes [36,[50][51][52][53][54]. In general, they all have proinflammatory effects, with both pro-and anti-apoptotic roles for some of them.…”

Section: Discussionmentioning

confidence: 99%

“…Shorter-chain-containing Cer are known to be more bioactive than the longer-chain species. The interconvertibility of these molecules and their biological effects often oppose each other, giving rise to the concept of a 'sphingolipid rheostat,' which maintains the balance of these molecules and thus cellular homeostasis [50,55]. Cytokines and activated tumor necrosis factor receptors (TNFR) have been shown to activate aSMases, which, in turn, convert membrane-bound SM to Cer during the early stages of injury [56][57][58].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mouse Model of Nitrogen Mustard Ocular Surface Injury Characterization and Sphingolipid Signaling

Basu,

Prislovsky,

Lenchik

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Vesicating chemicals like sulfur mustard (SM) or nitrogen mustard (NM) can cause devastating damage to the eyes, skin, and lungs. Eyes, being the most sensitive, have complicated pathologies that can manifest immediately after exposure (acute) and last for years (chronic). No FDA-approved drug is available to be used as medical counter measures (MCMs) against such injuries. Understanding the pathological mechanisms in acute and chronic response of the eye is essential for developing effective MCMs. Here, we report the clinical and histopathological characterization of a mouse model of NM-induced ocular surface injury (entire surface) developed by treating the eye with 2% (w/v) NM solution for 5 min. Unlike the existing models of specific injury, our model showed severe ocular inflammation, including the eyelids, structural deformity of the corneal epithelium and stroma, and diminished visual and retinal functions. We also observed alterations of the inflammatory markers and their expression at different phases of the injury, along with an activation of acidic sphingomyelinase (aSMase), causing an increase in bioactive sphingolipid ceramide and a reduction in sphingomyelin levels. This novel ocular surface mouse model recapitulated the injuries reported in human, rabbit, and murine SM or NM injury models. NM exposure of the entire ocular surface in mice, which is similar to accidental or deliberate exposure in humans, showed severe ocular inflammation and caused irreversible alterations to the corneal structure and significant vision loss. It also showed an intricate interplay between inflammatory markers over the injury period and alteration in sphingolipid homeostasis in the early acute phase.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mouse Model of Nitrogen Mustard Ocular Surface Injury Characterization and Sphingolipid Signaling

Basu,

Prislovsky,

Lenchik

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Sphingolipids (SPLs) play roles in cell signaling, inflammation, and apoptosis 47 and Cer is likely to assist in maintaining MG morphology and preventing inflammation. 48 Cers are also the central intermediates of sphingolipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Meibomian Gland Shortening Is Associated With Altered Meibum Composition

Iqbal,

Stapleton,

Masoudi

et al. 2024

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose The purpose of this study was to investigate differences in the composition of meibum extracted from human meibomian glands displaying different morphological characteristics. Methods Adult participants with evidence of meibomian gland shortening were enrolled. Glands were observed using infrared meibography, and meibum was collected from one short and one long gland from the lower eyelid of the same eye. Total protein concentration was evaluated using the detergent compatible ( DC ) protein assay and lipid analysis was performed using liquid chromatography mass spectrometry. Results Fifteen participants (8 women and 7 men) completed the study (mean age = 34.7 ± 7.7 years). The average volume of meibum collected from the short and long glands was 0.02 ± 0.01 and 0.05 ± 0.03 µL, respectively ( P = 0.01). Average protein concentration in the short glands was significantly higher compared to the long glands (0.10 ± 0.03 vs. 0.08 ± 0.02 mg/mL, P = 0.01). Among the non-polar lipids, the mole percent of cholesterol esters (CEs; P = 0.02), triacylglycerols (TAGs; P = 0.04), and ceramide (Cer; P = 0.03) was significantly lower in short glands compared with long glands. Among the polar lipids, the mole percent of (O-acyl)-ω-hydroxy fatty acid (OAHFA; P = 0.01) was significantly lower in short glands, whereas phosphatidylcholine (PC; P = 0.02) and sphingomyelin (SM; P = 0.01) were significantly higher in short glands than long glands. Conclusions Meibum composition differed between short and long glands. The lower mole percent of CE, TAG, OAHFA, and Cer and a higher mole percent of PC and SM among short glands may indicate disease activity. This information may clarify the natural history of meibomian gland dysfunction and future targets for therapy.

show abstract

“…[ 1 ] Inflammation occurs in response to a weakened immune system and invasion of microorganisms. [ 6 7 ] Effective eyelid hygiene is important to reduce bacterial overgrowth and maintain ocular surface health. This article summarizes eyelid cleaning and related content in recent years [ Fig.…”

mentioning

confidence: 99%

Eyelid cleaning: Methods, tools, and clinical applications

Zhang,

Wang,

Gao

2023

Indian Journal of Ophthalmology

View full text Add to dashboard Cite

Nowadays, people give more importance and pay closer attention to the condition of their eyelids and lid margins. This increased recognition of eyelid hygiene is due to the growing awareness that improper eyelid cleaning might lead to various ocular surface diseases such as blepharitis and meibomian gland dysfunction. These ocular surface diseases can greatly affect people's quality of life. This article reviews the latest procedures for proper eyelid cleaning, including indications, methods, tools, detergents, and clinical applications, to maintain a healthy ocular surface and assist in the treatment of dry eye and blepharitis.

show abstract

The role of sphingolipids in meibomian gland dysfunction and ocular surface inflammation

Cited by 10 publications

References 136 publications

Mouse Model of Nitrogen Mustard Ocular Surface Injury Characterization and Sphingolipid Signaling

Mouse Model of Nitrogen Mustard Ocular Surface Injury Characterization and Sphingolipid Signaling

Meibomian Gland Shortening Is Associated With Altered Meibum Composition

Eyelid cleaning: Methods, tools, and clinical applications

Contact Info

Product

Resources

About