Abstract
Purpose :
Alternative hyperoxia/hypoxia change is specifically toxic to the retinal development, which may be important in the progress of retinopathy of prematurity (ROP). The present study examines the metabolic components with molecular weights < 1.5 kDa of rat bloods treated with dynamic oxygen concentrations in order to find potential biomarkers for ROP.
Methods :
Rat pups were exposed to hyperoxia (80% oxygen) for 5 days from P7 to P12, with half sacrificed for blood samples at the end of the period. The rests were returned to room air for another 5 days, and sacrificed for blood samples at the time point of P17. Rat pups that lived in room air were sampled in parallel in order to match the time points. The sample derivatizations and injections were performed using a robotic multipurpose sample MPS2 with dual heads (Gerstel, Muehlheim, Germany). Metabolites were annotated with mammalian metabolite database JiaLabTM using a strict matching algorithm incorporated in XploreMET software that uses both retention times and fragmentation patterns in the mass spectrum.
Results :
Total 214 chemicals were detected with 122 ones annotated which were consisted of amino acids 38%, carbohydrates 19%, organic acids 17%, fatty acids 11%, lipids 5%, nucleotides 3% and others 7%. Multiple group comparisons (control and treatment groups in P12 and P17, respectively) showed four separated subgroups in PCA plot by using PLS-DA. Different metabolites between control and treatment groups in P12 were linked to 9 metabolic pathways and those in P17 linked to 10 ones.
Conclusions :
Metabolomic analysis of the retina in response to prolonged hyperoxia demonstrated a temporal pattern involving regulation of angiogenic factors and the influence of inflammatory cells, and provided insight into the mechanisms involved in the two phases of response. These findings should contribute to the understanding of the pathological conditions in ROP.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.