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Published on: November 12, 2017
Alteration of Tear Metabolomics Profiling in Infants With Retinopathy of Prematurity
Zixin Fan1, Shuo Yang1, Xiaofeng Lu1
1Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, Guangdong, China.
Insights
Tear metabolomic profiling identified specific biomarkers for retinopathy of prematurity (ROP) in infants. These findings may lead to noninvasive screening tools for ROP diagnosis.
Area of Science:
- Ophthalmology
- Neonatology
- Biochemistry
Background:
- Retinopathy of prematurity (ROP) is a leading cause of visual impairment in premature infants.
- Early detection and intervention are crucial for preventing severe visual outcomes.
- Current diagnostic methods may be invasive or require specialized equipment.
Purpose of the Study:
- To investigate the metabolomic profile of tears in infants with ROP.
- To identify noninvasive tear biomarkers for ROP detection.
- To correlate tear metabolite levels with ROP severity.
Main Methods:
- Prospective study of 47 premature infants (94 eyes).
- Tear samples collected using Schirmer strips after topical anesthesia.
- Untargeted metabolomic analysis performed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).
Main Results:
- 145 metabolites quantified; several were significantly upregulated or downregulated in ROP infants.
- Specific metabolites like 3,5-di-tert-butyl-4-hydroxybenzaldehyde, caffeine, and trehalose were upregulated.
- Uric acid, dihomo-γ-linolenic acid, and 6-keto-prostaglandin F1 alpha were downregulated; 6-keto-prostaglandin F1 alpha showed high diagnostic performance (AUC=0.893).
Conclusions:
- Dysregulated tear metabolites correlate with ROP severity.
- These metabolites show potential as noninvasive biomarkers for ROP.
- Tear metabolomics may serve as a complementary screening tool for ROP.
Purpose:
The purpose of this study was to investigate the characteristics of metabolomic profile in the tears from infants with retinopathy of prematurity (ROP) and further define noninvasive biomarkers.
Methods:
This prospective study included 94 eyes from 47 premature infants. Tear samples from 23 infants with ROP (15 treatment-requiring ones [ROP (t)] and 8 non-treatment-requiring ones [ROP (nt)]) and 24 infants without ROP were collected with Schirmer strips after topical anesthesia. Detailed fundus examination upon pupil dilation were conducted, with data on demographics and birth history recorded. Untargeted tear metabolomic analysis based on ultra-performance liquid chromatography-mass spectrometry was performed.
Results:
Adjusted by sex, postmenstrual age, gestational age, and birth weight, among 145 metabolites quantified, 3,5-di-tert-butyl-4-hydroxybenzaldehyde, caffeine, and trehalose were identified to be upregulated in the tears from infants with ROP when compared to those from premature infants with non-ROP, whereas uric acid, dihomo-γ-linolenic acid, nootkatone, pyridoxal, ornithine, 6-keto-prostaglandin F1 alpha, adenosine, and tetrahydrocortisol were downregulated (all adjusted false discovery rate [FDR adj] < 0.05). Nine and one dysregulated metabolites were further found in the ROP (t) and ROP (nt) subgroups, respectively. Some of these metabolites exhibited expression levels correlated with postmenstrual age, gestational age, birth weight, and ROP severity in varying degrees. The dysregulated tear metabolites were fundamentally related to vitamin B6, purine, caffeine, arginine, and starch and sucrose metabolism pathways. The 6-keto-prostaglandin F1 alpha obtained the best performance in classifying premature infants with and without ROP (area under the curve [AUC] of 0.893 [range = 0.800-0.986], P < 0.001).
Conclusions:
Dysregulated tear metabolites in ROP exhibited abundance correlated with severity of the disease and might be noninvasive biomarkers that potentially serve as complementary screening tools.
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