Recent Advances in Proteomics-Based Approaches to Studying Age-Related Macular Degeneration: A Systematic Review

Abstract

Age-related macular degeneration (AMD) is a common ocular disease characterized by degeneration of the central area of the retina in the elderly population. Progression and response to treatment are influenced by genetic and non-genetic factors. Proteomics is a powerful tool to study, at the molecular level, the mechanisms underlying the progression of the disease, to identify new therapeutic targets and to establish biomarkers to monitor progression and treatment effectiveness. In this work, we systematically review the use of proteomics-based approaches for the study of the molecular mechanisms underlying the development of AMD, as well as the progression of the disease and on-treatment patient monitoring. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guidelines were followed. Proteomic approaches have identified key players in the onset of the disease, such as complement components and proteins involved in lipid metabolism and oxidative stress, but also in the progression to advanced stages, including factors related to extracellular matrix integrity and angiogenesis. Although anti-vascular endothelial growth factor (anti-VEGF)-based therapy has been crucial in the treatment of neovascular AMD, it is necessary to deepen our understanding of the underlying disease mechanisms to move forward to next-generation therapies for later-stage forms of this multifactorial disease.

Posttranslational modifications of proteins in diseased retina

“…Recent developments in proteomic research have made it possible to identify a set of proteins differentially posttranslationally modified in diseased retinas ( Garcia-Quintanilla et al, 2022 ; Lam et al, 2022 ; Lee et al, 2022 ; Nattinen et al, 2022 ; Smyczynska et al, 2022 ; Zhou H. et al, 2022 ). However, despite advancements in molecular knowledge regarding the retinal pathobiology of ocular diseases, the question of whether the differential expression of proteins associates with altered activity remains unaddressed.…”

Multiplexed plasma protein classifiers for the diagnosis of age‐related macular degeneration

“…Alternative proteomics technologies are also being studied. 5 One of which is the blood-based multiple reaction monitoring-mass spectrometry (MRM-MS) assay where the peptides of plasma proteins can be detected for inspection, discovery and validation of plasma protein biomarkers. 6 We subjected 913 clinical plasma samples to a 7plex MRM-MS assay (Figure 1 and Table S1) that contained three peptides of the corresponding three proteins (IGFBP2, SELE and THBS1) and four CFH variants of two risk alleles (rs800292:p.Val62Ile and rs1061170:p.Tyr402His 1 ).…”

“…We thank Mr. Daniel Lee for English proofing. Hee-Sung Ahn 1,2 Youngju Lee 3 Hyeong Min Kim 4 Shinyeong Ju 1 Seonjeong Lee 1,5 Hyeon-Gyo Jeong 1 Sang Jun Park 4 Kyu Hyung Park 4 Junyeop Lee 6 Joo Yong Lee 6 Se Joon Woo 4 Cheolju Lee 1,3,5…”

“…Alternative proteomics technologies are also being studied. 5 One of which is the blood‐based multiple reaction monitoring‐mass spectrometry (MRM‐MS) assay where the peptides of plasma proteins can be detected for inspection, discovery and validation of plasma protein biomarkers. 6 …”

Oxidative Stress, Persistent Inflammation and Blood Coagulation Alterations in Serum Proteome of Patients with Neovascular Age-Related Macular Degeneration

“…The etiology of AMD is not fully understood, yet it is known to be a multifactorial disease, with strong genetic and environmental risk factors, where chronic oxidative stress, impaired clearance and prolonged inflammation result in pathological choroidal neovascularization [2,3]. A number of proteomic studies on AMD have already been conducted, with sometimes conflicting results, yet there are some patterns in the identified proteins and the metabolic pathways that they are involved in that support our current knowledge of the disease's etiology [4][5][6][7]. In our previous studies, we focused on the tear film proteome, providing interesting findings [8][9][10].…”