Abstract
Purpose: Diabetes mellitus (DM) is characterized by high blood sugar levels over a prolonged period. Long term complications include but not limited heart disease, stroke, kidney failure, and ocular damage. An estimated 382 million people are diagnosed with Type 2 DM accounting for 90% of the cases. Common corneal dysfunctions associated with DM result in impaired vision due to decreased wound healing, corneal edema, and altered epithelial basement membrane. Lipids play a fundamental role in tissue metabolism and disease states. We attempt to determine the role of sphingolipids (SPL) in human Type I and Type II diabetic corneas.
Materials and Methods: Cadaver corneas from healthy (non-diabetic/no ocular trauma), Type I (T1DM), and Type II diabetic (T2DM) donors were obtained and processed for lipidomics using LC-MS/MS.
Results: Our data show significant differences in the SPL composition between control, T1DM and T2DM corneas. Both T1DM and T2DM showed a 10-folddownregulation of sphingomyelin(SM), 5-fold up regulation of Ceramides (Cer) and 2-fold upregulation of monohexosylceramides (MHC). Differences were also seen in total amounts of SPL where Cer was increased by approximately 3 fold in both T1DM and T2DM where SM decreased by 50% in both T1DM and T2DM when compared to healthy controls. No differences were seen in MHC amounts.
Conclusions: Overall, our data indicate major differences in SPL distribution in human diabetic corneas. Information on the sphingolipids role in cornea, corneal cell physiology, and diseases are very limitedwhich highlights the importance of these findings.
Declaration of interest
The authors declare that there is no conflict of interest.
This work was supported by research grants from the Veteran’s Administration (VA Merit Review I BX001792 (CEC) and a Research Career Scientist Award 13F-RCS-002(CEC)); from the National Institutes of Health via HL125353(CEC), CA154314 (C.E.C),EY020886 (D.K), EY023568 (D.K), and NH1C06-RR17393 (to Virginia Commonwealth University for renovation); from unrestricted grant from Research to Prevent Blindness (New York, NY, USA). Services and products in support of the research project were generated by the VCU Massey Cancer Center Shared supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30 CA016059. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government.