Abstract
Purpose :
To characterize the plasma lipid profiles of patients with Bietti's crystalline dystrophy (BCD).
Methods :
The Case-control cross-sectional study prospectively recruited 64 participants with genetically confirmed BCD and 64 healthy controls with age, gender, and body mass index matched for each patient. All participants were genetically confirmed by CYP4V2 gene sequencing and underwent complete retinal imaging examinations for evaluation of chorioretinopathy. Fasting blood samples of BCD patients and controls were collected, and plasma was analyzed for routine lipid profiles. Long chain polyunsaturated fatty acids (LCPUFA) and associated eicosanoid metabolites were evaluated by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The levels of plasma lipids in participants with BCD was compared with controls and evaluated for correlation with severities of chorioretinopathy.
Results :
Routine lipids profiles showed elevated plasma levels of triglyceride (P=0.043) and low-density lipoprotein cholesterol (P=0.024) in BCD patients. Lipidomics showed significantly decreased levels of ω-3 LCPUFA including docosahexaenoic acid (DHA, 22:6, P=0.00068) and eicosapentaenoic acid (EPA, 20:5, P=0.0016), as well as ω-6 LCPUFA arachidonic acid (ARA, 20:4, P<0.0001) in BCD patients. Eicosanoid metabolites, either derived from ω-3 and/ or ω-6 LCPUFAs via cyclooxygenase (COX) or lipoxygenase (LOX) pathways, including 5-HEPE, 12-HEPE, 13-HDHA, 15-HETE, 12-HETE, 5-HETE, 6k-PGF1a, PGE2, PGJ2, and TXB2, exhibited significant differences (P<0.0001) between BCD patients and healthy controls. Meanwhile, increases in plasma levels of oleic acid (18:1, ω-9 monounsaturated fatty acid, P=0.020), 12,13-EpOME (linoleic acid (18:2) metabolite through cytochrome P450 (CYP) pathway, P=0.012) and 11,12-DHET (ARA metabolite through CYP pathway, P=0.0043) were found in BCD patients.
Conclusions :
BCD patients demonstrated substantial decrease in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA), as well as their downstream mediators via COX and LOX pathways, suggesting that these metabolites might be implicated in BCD pathogenesis and could serve as systemic biomarkers and therapeutic targets of the disease.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.