Abstract
Purpose :
Neovascular age related macular degeneration (AMD) is a major cause of irreversible blindness in elderly population in developed countries. AMD etiopathology is multifactorial with strong environmental and genetic component, but the its underlying molecular pathways are still unknown. We conducted a proteomic analysis of blood serum in advanced neovascular AMD in order to understand better the pathomechanism of the disease.
Methods :
Blood serum from 132 age and gender matched patients was collected. Control group consisted of 58, and AMD group of 74 patients. Control group consisted of patients scheduled for cataract surgery who showed no other ocular pathology. AMD group consisted of advanced neovascular AMD patients receiving ant-VEGF treatment, all in active phase of the disease. The samples were analyzed by LC-MS using a timsTOF Pro (Bruker Daltonik, Bremen, Germany) which was coupled online to a nanoElute nanoflow liquid chromatography system (Bruker Daltonik, Bremen, Germany). The LC/MS data were searched against the human Uniprot database (20,384 entries), with PEAKS X+ software version 10.5 (Bioinformatics Solutions, Waterloo, ON, Canada).
Results :
In total, 748 protein groups were identified. Label-free quantification revealed 17 differentially expressed proteins comparing the blood serum of both groups. There were 11 proteins upregulated in the AMD group, whereas 6 were downregulate. Main functions and common pathways of different proteins were determined by STRING database. The upregulated proteins were: Retinol-binding protein 4
, Inter-alpha-trypsin inhibitor heavy chain H2, Complement C1q subcomponent subunit B, Apolipoprotein A-II, Inter-alpha-trypsin inhibitor heavy chain H1, Hemopexin, Apolipoprotein B-100, Alpha-1-acid glycoprotein 1, Plasma protease C1 inhibitor, Albumin, and Protein Z-dependent protease inhibitor.
The downregulated proteins were: Prothrombin, Properdin, Coagulation factor XIII A chain, Alpha-1-antitrypsin, Trypsin-1, and Fibrinogen alpha chain.
The dysregulated proteins were involved in impaired cellular transportation, trypsin metabolism, coagulation balance, lipid metabolism, and inflammation-related pathways.
Conclusions :
Proteomic serum analysis may open new ways to understand AMD pathology, its progression and to analyze treatment responses.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.