Can Aqueous Proteomics Predict the Recurrence of Rhegmatogenous Retinal Detachment?

Purpose: To explore whether the proteome of aqueous collected during primary repair of rhegmatogenous Retinal Detachment (RD), differs between patients who experience recurrency (Recurrent RD Group) and those who do not (No Recurrent RD Group). Methods: The aqueous proteome collected during primary surgery of 13 patients undergoing Recurrent RD was compared to 11 age and sex-matched patients successfully operated for rhegmatogenous RD with no recurrency after 12-months follow-up, regardless of surgical technique. A label-free shotgun proteomics approach identified and quantified the repertoire of aqueous proteins. Differential protein expression between Groups was determined using the Limma moderated Bayesian t-test, followed by False Discovery Rate (FDR) validation using Storey's q-test. Results: Aqueous profiling identified >800 unique proteins; 45 exclusive to the Recurrent RD group, 10 exclusive to the no Recurrent RD group and 33 differently expressed between groups (log2fold-change≥∣0.57∣, FDR≤0.05). Proteins upregulated in Recurrent RD patients, clearly pointed to mechanisms of cell:cell and cell:matrix adhesiveness and mechano-transduction signalling pathways. Upregulated proteins included extracellular matrix components such as type I and IV collagens, bi-glycan, proteoglycans, and cell-membrane adhesion molecules. Conclusion: The baseline aqueous composition of RD patients that will eventually develop recurrency, differs significantly from those who will not, and already contains molecular signatures that may help identify the risk of recurrency at the time of primary repair. While acknowledging the pilot nature of the study, our findings strongly suggest that Recurrent RD is associated with cell adhesiveness pathways early alterations, offering targets for prognostic assessment and therapy.