Metabolomic Profile in the Aqueous Humor of Congenital Ectopia Lentis

Abstract

Purpose

To explore the metabolic profiles in the aqueous humor (AH) of patients with congenital ectopia lentis (CEL).

Methods

We conducted a comprehensive analysis of the metabolites of AH samples of patients with CEL (n = 22) and age-matched patients (n = 22) with congenital cataract by ultra-high performance liquid chromatography tandem-mass spectrometry. The metabolomic characteristics were visualized by principal component analysis, orthogonal partial least squares discriminant analysis and heat map. The levels of the differential metabolites were also compared between CEL patients with and without FBN1 mutations. Pathway enrichment analysis was performed by using Kyoto Encyclopedia of Genes and Genomes. Receiver operating characteristic analysis was performed to select potential biomarkers.

Results

There were 175 differential metabolites identified between the two groups. Eight metabolites were found to be potential biomarkers in AH of CEL patients. The CEL group showed a significant increase in α-ketoglutarate and decrease in citrate, suggesting that the tricarboxylic acid (TCA) cycle was disturbed. l-proline, prolyl-hydroxyproline, and l-histidine were reduced, which prompted enhanced degradation of microfibrils and collagen. Insidious retinal nerve damage was implied because N-Acetyl-aspartylglutamic acid and N-Acetyl-l-aspartic acid were found to be significantly increased. Pathway enrichment analysis indicated that disturbances in amino acid metabolism and carbohydrate metabolism were the key processes in the pathogenesis of CEL and that TCA cycle disorder may be the driving force behind disease occurrence.

Conclusion

These data reveal the characteristics in the metabolomic profiles of the AH of CEL patients, which help provide insights into the pathogenesis of this rare disease.

Keywords:

• Congenital ectopia lentis
• metabolism
• aqueous humor
• FBN1
• lens disease

Author contributions

DYZ and GMJ designed the study. LYL and YQL wrote and revised the manuscript. LYL, DWG, HWY and HTQ collected the aqueous humor samples. LYL and BZ analyzed the data and visualized. YQL, DYZ and GMJ provided critical review for the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, DY Zheng or GM Jin, upon reasonable request.

Additional information

Funding

This study was supported by National Natural Science Foundation of China [81900841], and Guangdong Basic and Applied Basic Research Foundation [2021A1515011673; 2022A1515011181].