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DIA Comparative Proteomic Analysis of Retro-oil Fluid and Vitreous Fluid From Retinal Detachment Patients.

ABSTRACT: Objectives: There have been reports of unexplained visual loss following intra-ocular silicone oil (SiO) tamponade in retinal detachment patients, yet the underlying mechanism is unknown. The aim of this study was to investigate the mechanisms behind retinal toxicity following intra-ocular SiO tamponade in retinal detachment patients. Methods and Results: Vitreous fluid samples were acquired from 27 patients (27 eyes). Twelve eyes for data-independent acquisition (DIA) were divided into four groups: pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RD group), SiO removal after successful retinal reattachment (SO group), cataract surgery after successful retinal reattachment with sterilized air tamponade (FA group), and PPV for epiretinal membrane (ERM group). The remaining 15 eyes were used for enzyme-linked immunosorbent assay analysis. DIA was combined with two-dimensional liquid chromatography-tandem mass spectrometry to find expression changes in the proteome of vitreous. Mean number mass spectra, statistically differentially expressed proteins, gene ontology (GO), pathway representations, and protein interactions were analyzed. GO analysis showed that the protein categories of synapse organization, cell adhesion, and regulation of cell migration in the SO group were differentially expressed compared to the control or FA groups (p < 0.05). Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, lysosome and cell adhesion were found to be significantly enriched in the SO group compared to the FA and control groups (p < 0.05). Cadherin 2, transferrin, and lysosome function may partially contribute to silicone oil-related vision loss. Conclusion: Vision loss-inducing novel molecular signatures and pathways that may be associated with SiO toxicity were identified. Transferrin may be a potential visual outcome biomarker for SiO tamponade.

SUBMITTER: Shu Y

PROVIDER: S-EPMC8678117 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionRetinal detachment is a sight-threatening emergency, with more than half of those affected suffering permanent visual impairment. A diagnostic test to identify eyes at risk before vision is threatened would enable exploration of prophylactic treatment. This report presents the use of irregularities in retinal shape, quantified from optical coherence tomography (OCT) images, as a biomarker for retinal detachment.MethodsOCT images were taken from posterior and mid-peripheral retina of 264 individuals [97 after a posterior vitreous detachment (PVD), 99 after vitrectomy for retinal detachment and 68 after laser for a retinal tear]. Diagnoses were taken from history, examination and OCT. Retinal irregularity was quantified in the frequency domain, and the distribution of irregularity across the regions of the eye was explored to identify features exhibiting the greatest difference between retinal detachment and PVD eyes. Two of these features plus axial length were used to train a quadratic discriminant analysis classifier. Classifier performance was assessed by its sensitivity and specificity in identifying retinal detachment eyes and visualised with a receiver operating characteristic (ROC) curve.ResultsValidation set specificity was 84% (44/52 PVD eyes correctly labelled) and sensitivity 35% (23/64 retinal detachment eyes identified, p = 0.02). Area under the ROC curve was 0.75 (95% confidence intervals 0.58-0.85). Retinal detachment eyes were significantly more irregular than PVD eyes in the superior retina (0.70 mm versus 0.49 mm, p < 0.05) and supero-temporal retina (1.12 mm versus 0.80 mm, p < 0.05). Lower sensitivity (16/68, 24%) was seen for eyes with a retinal tear without detachment, that were intermediate in size between retinal detachment and PVD eyes. Axial length on its own was a poor classifier. Neither irregularity nor classification were affected by surgery for retinal detachment or the development of PVD.ConclusionsThe classifier identified 1/3 of retinal detachment eyes in this sample. In future work, these features can be evaluated as a test for retinal detachment prior to PVD.

Project description:PurposeTo compare baseline levels of exploratory biomarkers in the vitreous fluid of patients with primary retinal detachment who subsequently develop proliferative vitreoretinopathy (PVR) versus those who do not.MethodsIn this exploratory case-control study, we evaluated the baseline protein biomarker levels from a biobank containing the vitreous fluid of patients who had undergone primary pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment. Undiluted samples were collected at the time of PPV and stored at -80°C. Samples from 13 patients who developed PVR within 6 months (PVR group) and 13 age- and gender-matched controls who did not develop PVR (control group) were included. Protein abundance levels were evaluated using a proximity extension assay, and a confirmatory enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of vimentin.ResultsBaseline vimentin (Normalized Protein eXpression [NPX], 8.6 vs. 6.4, P < 0.0001) and heme oxygenase 1 (NPX 8.9 vs. 7.0, P < 0.001) levels were found to be elevated in vitreous fluid of patients who subsequently developed PVR compared to those who did not. Confirmatory analysis using ELISA demonstrated mean vimentin concentrations of 7254 vs. 2727 ng/mL in the PVR versus control groups (P = 0.0152). The odds ratio for developing PVR was 14 (confidence interval, 1.4-168; P = 0.03), assuming a baseline vimentin threshold of 7500 ng/mL.ConclusionsVimentin is an intermediate filament protein expressed by retinal glial cells, and our data combined with prior evidence suggest that it may serve as an early vitreous biomarker for subsequent PVR formation and reactive gliosis. Furthermore, we found, for the first time, elevated baseline levels of heme oxygenase 1, a measurable indicator of oxidative stress.Translational relevanceOur positive findings could impact clinical care for retinal detachment patients by facilitating risk stratification for targeted interventions or closer monitoring in those at the highest risk of developing PVR.

Project description:PurposeTo investigate the incidence, seasonal variation, and differences among age, sex, and race for rhegmatogenous retinal detachment (RRD) repair, retinal break (RB) treatment, and posterior vitreous detachment (PVD) in the Intelligent Research in Sight (IRIS) Registry.DesignRetrospective database study.ParticipantsPatients in the IRIS Registry who underwent RRD repair, RB treatment, or cataract surgery (CS) based on Current Procedural Terminology codes and PVD diagnosis based on International Classification of Diseases, Ninth and Tenth Revision, codes.MethodsDaily incidence rates were defined as the ratio of patients who underwent RRD repair or RB treatment and patients with a diagnosis of PVD to the total number of patients followed on a given day within the IRIS Registry. The CS group was included as a comparison for seasonal variation. Rates were stratified by decade of life, sex, and race.Main outcome measuresTime series trends for incidence rates of RRD, RB, and PVD.ResultsA total of 7 115 774 patients received a diagnosis of incident PVD, 237 646 patients underwent RRD repair, and 359 022 patients underwent RB treatment. Also included were 5 940 448 patients who underwent CS. The mean daily incidence for RRD repair, RB treatment, PVD diagnosis, and CS were 0.46 per 100 000 patients, 0.70 per 100 000 patients, 13.90 per 100 000 patients, and 11.80 per 100 000 patients, respectively. Men showed higher incidence of RRD repair and RB treatment than women, whereas women showed higher incidence of PVD diagnosis. Rhegmatogenous retinal detachment incidence was higher in White people compared with other races. Seasonal decreases in PVD, RB treatment, RRD repair, and CS corresponded to national holidays, with larger decreases in winter months. Kaplan-Meier estimates showed that RRD repair and RB treatment typically occurred within 60 days of PVD diagnosis.ConclusionsWithin the IRIS Registry, the highest incidence of RRD was in the 6th and 7th decade of life. There was a higher incidence of RRD repair and RB treatment in men compared with women. The seasonal variation associated with national holidays was less pronounced for RRD repair and RB treatment.

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DIA Comparative Proteomic Analysis of Retro-oil Fluid and Vitreous Fluid From Retinal Detachment Patients.

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