Vitreous humor proteome: unraveling the molecular mechanisms underlying proliferative and neovascular vitreoretinal diseases

Santos, Fátima Milhano; Ciordia, Sergio; Mesquita, Joana; Sousa, João Paulo; Paradela, Alberto; Tomaz, Cândida T.; Passarinha, Luís A.

doi:10.1007/s00018-022-04670-y

Cited by 15 publications

(11 citation statements)

References 361 publications

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“…However, the role of complement and coagulation cascades in vitreoretinal diseases could be more complex, as they may be involved in pathological processes shared by DR/PDR, AMD, and RRD/PVR, as recently reviewed by our group ( 86 ). In healthy neurosensory tissues, activated complement components can act as neurotrophic and anti-inflammatory factors, promoting cell survival and tissue remodeling.…”

Section: Discussionmentioning

confidence: 92%

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases

et al. 2023

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IntroductionDiabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in middle-income and industrialized countries. Anti-VEGF therapies have improved the management of neovascular AMD (nAMD) and proliferative DR (PDR), no treatment options exist for the highly prevalent dry form of AMD.MethodsTo unravel the biological processes underlying these pathologies and to find new potential biomarkers, a label-free quantitative (LFQ) method was applied to analyze the vitreous proteome in PDR (n=4), AMD (n=4) compared to idiopathic epiretinal membranes (ERM) (n=4). Results and discussionPost-hoc tests revealed 96 proteins capable of differentiating among the different groups, whereas 118 proteins were found differentially regulated in PDR compared to ERM and 95 proteins in PDR compared to dry AMD. Pathway analysis indicates that mediators of complement, coagulation cascades and acute phase responses are enriched in PDR vitreous, whilst proteins highly correlated to the extracellular matrix (ECM) organization, platelet degranulation, lysosomal degradation, cell adhesion, and central nervous system development were found underexpressed. According to these results, 35 proteins were selected and monitored by MRM (multiple reaction monitoring) in a larger cohort of patients with ERM (n=21), DR/PDR (n=20), AMD (n=11), and retinal detachment (n=13). Of these, 26 proteins could differentiate between these vitreoretinal diseases. Based on Partial least squares discriminant and multivariate exploratory receiver operating characteristic (ROC) analyses, a panel of 15 discriminatory biomarkers was defined, which includes complement and coagulation components (complement C2 and prothrombin), acute-phase mediators (alpha-1-antichymotrypsin), adhesion molecules (e.g., myocilin, galectin-3-binding protein), ECM components (opticin), and neurodegeneration biomarkers (beta-amyloid, amyloid-like protein 2).

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Section: Discussionmentioning

confidence: 92%

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases

et al. 2023

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“…Several studies have analyzed the vitreous proteome in patients with proliferative vitreoretinopathy (PVR) and provided new insights into the disease mechanisms . Among them, one study revealed stage-specific alterations of the vitreous proteome in patients with PVR .…”

Section: Vitreous Liquid Biopsy Proteomicsmentioning

confidence: 99%

“…Vitreous proteomics has been widely applied in age-related macular degeneration (AMD) and has significantly advanced our understanding of its pathophysiology. − Several biomarkers have been identified that can be useful to stratify disease stages, including dry and neovascular AMD . Multiple studies identified the complement system as a critical pathway in AMD, , which led to the development and recent approval of complement targeting drugs for geographic atrophy. , …”

Section: Vitreous Liquid Biopsy Proteomicsmentioning

confidence: 99%

Liquid Biopsy Proteomics in Ophthalmology

Wolf,

Franco,

Yip

et al. 2024

J. Proteome Res.

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Minimally invasive liquid biopsies from the eye capture locally enriched fluids that contain thousands of proteins from highly specialized ocular cell types, presenting a promising alternative to solid tissue biopsies. The advantages of liquid biopsies include sampling the eye without causing irreversible functional damage, potentially better reflecting tissue heterogeneity, collecting samples in an outpatient setting, monitoring therapeutic response with sequential sampling, and even allowing examination of disease mechanisms at the cell level in living humans, an approach that we refer to as TEMPO (Tracing Expression of Multiple Protein Origins). Liquid biopsy proteomics has the potential to transform molecular diagnostics and prognostics and to assess disease mechanisms and personalized therapeutic strategies in individual patients. This review addresses opportunities, challenges, and future directions of high-resolution liquid biopsy proteomics in ophthalmology, with particular emphasis on the large-scale collection of high-quality samples, cutting edge proteomics technology, and artificial intelligence-supported data analysis.

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“…6 Proteomic profiling analysis has been employed to investigate molecular changes in eye disease, while various studies have identified pathological expression features in the retina, choroid, or the entire posterior segment of the eyes in vitreoretinal diseases, which made it a valuable technology for the identification of differential expression in proteins. 7,8 The aqueous humor is generated from the blood through a pressure gradient and selectively transported by the cells of the ciliary body, 9 and the components in the aqueous humor have been reported to communicate with other intraocular fluid components or tissues. eye diseases, changes in the components of the aqueous humor occur in response to alterations in intraocular components.…”

Section: Introductionmentioning

confidence: 99%

“…Since abundant proteins and their interactions are regarded as the direct representatives of complex biochemical processes, proteomics bioinformatic analysis has the advantage of offering more specific information for understanding the difference in protein expression based on high-throughput technology . Proteomic profiling analysis has been employed to investigate molecular changes in eye disease, while various studies have identified pathological expression features in the retina, choroid, or the entire posterior segment of the eyes in vitreoretinal diseases, which made it a valuable technology for the identification of differential expression in proteins. , …”

Section: Introductionmentioning

confidence: 99%

Comparative Proteomic Analysis of Aqueous Humor Reveals Biochemical Disparities in the Eyes of High Myopic Patients

Du,

Liu,

Zhou

et al. 2024

J. Proteome Res.

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Myopia accounts for a significant proportion of visual lesions worldwide and has the potential to progress toward pathological myopia. This study aims to reveal the difference in protein content in aqueous humor between high myopic and nonhigh myopic patients, as well as better understand the dysregulation of proteins in myopic eyes. Aqueous humor was collected for liquid chromatograph mass spectrometer (LC/MS) analysis from 30 individual eyes that underwent phacoemulsification and intraocular lens (IOL) implantation. Results showed that a total of 190 differentially expressed proteins were identified, which revealed their involvement in cell metabolism, immune and inflammatory response, and system and anatomical structure. Further analysis focused on 15 intensively interacted hub proteins, encompassing functions related to complement cascades, lipoprotein metabolism, and fibrin biological function. Subsequent validations demonstrated elevated levels of APOE (apolipoprotein E), C3 (complement 3), and AHSG (α-2-HS-glycoprotein) in the high myopia group (31 eyes of cataracts and 45 eyes of high myopia with cataracts). AHSG had a significant positive correlation with axial length in high myopic patients, with good efficacy in distinguishing between myopic and nonmyopic groups. AHSG may be a potential indicator of the pathological severity and participator in the pathological progress of high myopia. This study depicted differential expression characteristics of aqueous humor in patients with high myopia and provided optional information for further experimental research on exploring the molecular mechanisms and potential therapeutic targets for high myopia. Data are available via ProteomeXchange with the identifier PXD047584.

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Vitreous humor proteome: unraveling the molecular mechanisms underlying proliferative and neovascular vitreoretinal diseases

Cited by 15 publications

References 361 publications

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases

Liquid Biopsy Proteomics in Ophthalmology

Comparative Proteomic Analysis of Aqueous Humor Reveals Biochemical Disparities in the Eyes of High Myopic Patients

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