Proteome and Metabolome of Subretinal Fluid in Central Serous Chorioretinopathy and Rhegmatogenous Retinal Detachment: A Pilot Case Study

Abstract

PurposeTo investigate the molecular composition of subretinal fluid (SRF) in central serous chorioretinopathy (CSCR) and rhegmatogenous retinal detachment (RRD) using proteomics and metabolomics.MethodsSRF was obtained from one patient with severe nonresolving bullous CSCR requiring surgical subretinal fibrin removal, and two patients with long-standing RRD. Proteins were trypsin-digested, labeled with Tandem-Mass-Tag and fractionated according to their isoelectric point for identification and quantification by tandem mass spectrometry. Independently, metabolites were extracted on cold methanol/ethanol, and identified by untargeted ultra-high performance liquid chromatography and high-resolution mass spectrometry. Bioinformatics analyses were conducted.ResultsIn total, 291 proteins and 651 metabolites were identified in SRF samples. Compared with RRD, 128 proteins (77 downregulated; 51 upregulated) and 76 metabolites (43 downregulated; 33 upregulated) differed in the SRF from CSCR. Protein and metabolites notably deregulated in CSCR were related to glycolysis/gluconeogenesis, inflammation (including serum amyloid P component, versican), alternative complement pathway (complement factor H and complement factor H–related protein), cellular adhesion, biliary acid metabolism (farnesoid X receptor/retinoid X receptor), and gluco- and mineralocorticoid systems (aldosterone, angiotensin, and corticosteroid-binding globulin).ConclusionsProteomics and metabolomics can be performed on SRF. A unique SRF sample from CSCR exhibited a distinct molecular profile compared with RRD.Translational RelevanceThis first comparative multiomics analysis of SRF improved the understanding of CSCR and RRD pathophysiology. It identified pathways potentially involved in the better photoreceptor preservation in CSCR, suggesting neuroprotective targets that will require additional confirmation.

Bullous Central Serous Chorioretinopathy: A Rare and Atypical Form of Central Serous Chorioretinopathy. A Systematic Review

“…Interestingly Kowalczuk et al compared proteins and metabolites of the SRF obtained from patients affected by bCSCR or RRD [ 15 ]. Downregulation of the alternative complement pathway was found in bCSCR.…”

“…Downregulation of the alternative complement pathway was found in bCSCR. It is involved in physiologic transport of ions and macromolecules, and it might cause fluid accumulation into subretinal space [ 15 ]. Furthermore, induced gluconeogenesis and glycolysis in bCSCR may promote cone photoreceptor’s survival [ 15 ].…”

“…It is involved in physiologic transport of ions and macromolecules, and it might cause fluid accumulation into subretinal space [ 15 ]. Furthermore, induced gluconeogenesis and glycolysis in bCSCR may promote cone photoreceptor’s survival [ 15 ]. Also, the farnesoid X receptor (FXR) pathway activated in bCSCR, highlighted other neuroprotective mechanisms.…”

“…Also, the farnesoid X receptor (FXR) pathway activated in bCSCR, highlighted other neuroprotective mechanisms. Additionally, proteins involved in cell migration and adhesion (e.g., opticin, myocilin, metalloproteinase-2), usually abundant in the vitreous, were reduced in bCSCR, justifying the better architecture preservation in this disease [ 15 ]. Finally, downregulation of steroid metabolism and microglia and lipid metabolism different activation were reported, confirming the different aetiopathogenesis between bCSCR and RRD [ 15 ].…”

“…Eight articles were excluded: six not written in English, 1 review papers and 1 ex vivo studies. After full-text evaluation, 34 studies about bCSCR were included [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 ].…”