June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Ocular Surface Sphingomyelinases, Meibum and Tear Sphingolipids, and Clinical Parameters of Meibomian Gland Dysfunction
Author Affiliations & Notes
  • Victor Sanchez
    New York University Grossman School of Medicine, New York, New York, United States
    Ophthalmology, Miami Veterans Administration Medical Center, Miami, Florida, United States
  • Anat Galor
    University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
    Ophthalmology, Miami Veterans Administration Medical Center, Miami, Florida, United States
  • Katherine Jensen
    Ophthalmology, Miami Veterans Administration Medical Center, Miami, Florida, United States
  • Koushik Mondal
    The University of Tennessee Health Science Center Department of Ophthalmology Hamilton Eye Institute, Memphis, Tennessee, United States
  • Nawajes A Mandal
    The University of Tennessee Health Science Center Department of Ophthalmology Hamilton Eye Institute, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Victor Sanchez None; Anat Galor None; Katherine Jensen None; Koushik Mondal None; Nawajes Mandal None
  • Footnotes
    Support  Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences R&D (CSRD) I01 CX002015 (Dr. Galor) and Biomedical Laboratory R&D (BLRD) Service I01 BX004893 (Drs. Galor and Mandal), Department of Defense Gulf War Illness Research Program (GWIRP) W81XWH-20-1-0579 (Dr. Galor) and Vision Research Program (VRP) W81XWH-20-1-0820 (Dr. Galor), National Eye Institute R01EY026174 (Dr. Galor) and R61EY032468 (Dr. Galor), NIH Center Core Grant P30EY014801 (institutional) and Research to Prevent Blindness Unrestricted Grant (institutional). National Eye Institute grants EY022071 and R01 EY031316 (Dr. Mandal); US Department of Defense office of the Congressionally Directed Medical Research Programs (CDMRP), Vision Research Program (VRP) grant W81XWH-20-1-0900 (Dr. Mandal).
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 426. doi:
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      Victor Sanchez, Anat Galor, Katherine Jensen, Koushik Mondal, Nawajes A Mandal; Ocular Surface Sphingomyelinases, Meibum and Tear Sphingolipids, and Clinical Parameters of Meibomian Gland Dysfunction. Invest. Ophthalmol. Vis. Sci. 2022;63(7):426.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The lipid composition of meibum and tears is believed to play a role in meibomian gland dysfunction (MGD) and dry eye (DE). Sphingomyelinases (SMase) are enzymes that participate in the metabolism of sphingolipids (SPL), which have structural and bioactive functions on the ocular surface. We prospectively analyzed the tears of individuals with good versus poor meibum quality and quantified the activity of SMases with acidic (aSMase) and neutral (nSMase) pH optimums. We predicted that SMase expression would differ in individuals with good versus poor meibum quality.

Methods :
Participants were grouped by meibum quality (n=25 controls; n=25 with poor quality, MGD group). Meibum was forcefully expressed and collected on a cotton swab and tears were collected on Schirmer strips. Activity of tear SMases were determined by Amplex™ Red Sphingomyelinase Assay Kit (Thermo Fisher). DE symptoms and signs were assessed in a comprehensive manner. First, SMase expression between the MGD and control groups was compared. Next, correlations were conducted to examine relationships between SMases and SPL composition determined previously from meibum and tears. Finally, linear regression analyses examined how DE symptoms/signs relate to SMase expression.

Results : The mean population age was 57 ± 9 years; 84% identified as male, and 38% as white. Demographics were similar between the groups. aSMases (23,748 RFU, IQR=26,392 vs. 4,205 RFU, IQR=13,341, p<0.001) and nSMases (30,893 RFU, IQR=51,181 vs. 0 RFU, IQR=6263, p<0.001) expression in tears was greater in the control versus MGD group. SMase expression correlated with compositional changes in meibum and tear SPL. In meibum, SMases positively correlated with Sph (aSMase, ρ=0.45, p<0.001; nSMase, ρ=0.45, p<0.001). In tears, SMase negatively correlated with SM (aSMase, ρ=-0.30, p<0.05; nSMase, ρ=-0.29, p<0.05) and positively with S1P (aSMase, ρ=0.51, p<0.001; nSmase, ρ=0.49, p<0.001). Higher nSMase expression correlated with more severe DE symptoms (Dry Eye Questoinnaire-5; ρ=0.29, p<0.05) but less severe meibomian dropout (nSmase, ρ=-0.35, p<0.05).

Conclusions : SMase expression was reduced in the tears of individuals with MGD and expression levels were associated with altered concentrations of SPLs in meibum and tears. Enzymes of SPL lipid metabolism, such as SMase, may represent a target of therapeutic intervention in the treatment of MGD.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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