Abstract
Purpose :
We performed a prospective observational clinical study to differentiate eyes that did and did not develop proliferative vitreoretinopathy (PVR) on the basis of the metabolites and cytokines in human vitreous samples taken at the time of rhegmatogenous retinal detachment (RRD) repair.
Methods :
Metabolomic analysis was performed on 66 vitreous samples, obtained at the start of pars plana vitrectomy from patients undergoing surgery for macular hole (n=21) and RRD (n=44), including patients who subsequently developed PVR (n=14) and patients who did not (n=31). One-dimensional 1H spectra were acquired at 298 °K with 128 scans using a standard Bruker NOESY 1D pulse sequence with pre-saturation water suppression Bruker DRX 600MHz NMR spectrometer equipped with a cryoprobe. Chemical shifts were calibrated with respect to the chemical shift position of the TMSP resonance.
Multiplexed immunoassays with fluorescent microspheres were used to perform cytokine analysis in MH (n= 45); RRD (n= 71) and PVR eyes (n=22). Different disease groups were analysed using both univariate and multivariable approaches.
Results :
High levels of 2-hydroxyvalerate, 2-phosphoglycerate, alanine, alloisoleucine, glutamine, histidine, methanol, urea, valine and myo-inositol predicted the development of post-operative PVR. Levels were lower in those eye with RD that did not develop PVR. Creatine was found to be higher in the MH group as compared to RD.
The cytokines IL-1β and IL-7 were found to be significantly higher in the PVR group compared to the RD group (P=0.02 and 0.03 respectively). IL1ra, IL7, IL8, IL9, IP10 and MIP1b was found to higher in the RD group compared to MH group.
Conclusions :
We report, for the first time, vitreous metabolic changes predicting PVR development. Through pathway analysis, increased histadine, glutamine, valine, alanine and isoleucine points to aminoacyl tRNA biosynthesis. High levels are predictive of PVR development. Upregulation is associated with increased protein synthesis required for proliferation of fibrocellular membranes in PVR.
The metabolite results are suggestive of increased glycolysis activity and glutamate signalling, associated with the enhanced cellular migration and proliferation plus excitotoxicity seen in PVR development.
The cytokines detected have a more proliferative than apoptotic profile, supporting the suggestion that the detected metabolic changes relate to cell migration and proliferation.
This is a 2021 ARVO Annual Meeting abstract.