Elevated Very-Long-Chain Ceramides in the Vitreous Humor of Patients With Proliferative Diabetic Retinopathy.

PURPOSE: To quantitate the levels of various ceramide species in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate the role of vitreal ceramides in the pathogenesis of PDR. STUDY DESIGN: A case control study. METHODS: We collected vitreous samples from 25 type 2 diabetes patients with PDR and 25 age- and sex-matched nondiabetic controls undergoing vitrectomy. The levels of ceramide species (C16:0, 18:0, 20:0, 22:0, 24:1, and 24:0) were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry with positive electrospray ionization mode. The correlation of baseline characteristics, blood test data, and clinical manifestation of PDR were analyzed with vitreal ceramides levels. RESULTS: The total level of ceramides was substantially higher in the PDR group than the control group (18.626 ± 19.264 versus 3.524 ± 2.456 pmol/mg protein; P < 0.001). Among ceramides of various acyl chain lengths, the increases of very-long-chain (VLC) ceramides (C22-C24) were more drastic than those of long-chain ceramides (C16-C20). In the PDR group, VLC ceramide species accounted for 76.1%, whereas in the control group, C16 ceramide predominated at 40.5%. Based on the multivariate linear regression analysis, diagnosis of diabetes (β = 14.5751; P = 0.0327) and lower body mass index (β = -2.1396; P = 0.0173) were significantly associated with higher level of VLC ceramides. Intravitreal injection of anti-VEGF leads to insignificant reduction of VLC ceramides (P = 0.068). CONCLUSIONS: Vitreal ceramide levels were elevated in diabetic subjects, especially the VLC species, which may contribute to the pathogenesis of diabetic retinopathy.