Proteomic analysis of aqueous humor proteins associated with neovascular glaucoma secondary to proliferative diabetic retinopathy

2020 ◽  
Vol 18 ◽  
Author(s):  
Ying Wang ◽  
Shaolin Xu ◽  
Junyi Li ◽  
Fujie Yuan ◽  
Yue Chen ◽  
...  

Objective:: Extensive retinal ischemia caused by proliferative diabetic retinopathy (PDR) may develop into neo-vascular glaucoma (NVG). We searched for the proteins which might participate in neovascularization through the analysis of aqueous humor (AH) proteomics in patients with NVG secondary to PDR to increasing the understanding of the possible mechanism of neovascularization. Methods:: We collected 12 samples (group A) of AH from patients with NVG secondary to PDR as the experimental group and 7 samples (group B) of AH from patients with primary acute angle-closure glaucoma (PAACG) & diabetes mellitus without diabetic retinopathy (NDR) as the control group. Differential quantitative proteome analysis of the aqueous humor samples was performed based on data-independent acquisition (DIA) method. The differentially expressed proteins were functionally annotated by Ingenuity Pathway Analysis (IPA). The important differentially expressed proteins were validated in another group (group A: 5 samples and group B: 5 samples) by parallel reaction monitor (PRM) approach . Results:: A total of 636 AH proteins were identified, and 82 proteins were differentially expressed between two groups. Functional annotation showed that the differentially expressed proteins were mainly associated with angiogenesis and cell migration. Signaling pathways analysis showed that the proteins up-regulated in group A were mainly related to Liver X re-ceptor/Retinoid X receptor (LXR/RXR) activation and acute reaction. Conclusions:: This study presented a pilot work related to NVG secondary to PDR, which provided a better understanding of the mechanisms governing the pathophysiology of NVG.

2016 ◽  
Vol 236 (2) ◽  
pp. 61-66 ◽  
Author(s):  
Jun Li ◽  
Wen-chao Hu ◽  
Hui Song ◽  
Jing-na Lin ◽  
Xin Tang

Purpose: To investigate chemerin in the vitreous bodies of patients with proliferative diabetic retinopathy (PDR) and determine the correlation between the levels of vitreous chemerin and vascular endothelial growth factor (VEGF). Methods: This study included 17 patients suffering from PDR and vitreous hemorrhage (VH) (group A), 21 patients with PDR and tractional retinal detachment (TRD) (group B) and 25 patients with idiopathic macular holes or preretinal membranes (control group). All vitreous samples were obtained through pars plana vitrectomy. Enzyme-linked immunosorbent assay and Western blot analysis were performed to evaluate the levels of vitreous chemerin and VEGF. Results: Vitreous concentrations of chemerin were significantly higher in PDR patients with VH and TRD than those in the controls [4.82 ng/ml (3.91-6.13) vs. 5.03 ng/ml (4.01-6.15) vs. 2.53 ng/ml (1.53-5.66), p = 0.025]. The ratio of vitreous chemerin to plasma chemerin concentration significantly differed between groups A and B and the control group [4.93% (4.69-5.34) vs. 4.98% (4.63-5.19) vs. 2.58% (1.78-4.58), p < 0.001]. Western blot results indicated that the levels of vitreous chemerin protein in PDR patients significantly increased compared with those in the controls. Spearman correlation analysis further showed that vitreous chemerin levels in patients with PDR were positively correlated with vitreous VEGF levels (r = -0.542, p < 0.001). Conclusions: Increased vitreous chemerin levels are associated with the development of PDR.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4297-4297
Author(s):  
Fan Yi Meng ◽  
Shuai Tian ◽  
Jia-ming Tang

Abstract Objective:The distinct proteins of leukemic cells were investigated by proteomics technology between AML-M2a patients before inductive treatments with evidently different duration of first continuous complete remission(CCR1) and AML-M2a patients at replase in order to find their relations with prognosis of AML-M2a. Methods:The bone marrow mononuclear cells(BMMNCs) from 17 cases of AML-M2a patients before inductive treatment were grouped with different duration of CCR1: group A with CCR1 duration exceeded 12 months(11 cases), group B within 6 months(6 cases), and group C was composed of 3 patients at replase among group B. The proteins of BMMNCs from all the patients were separated by two-dimensional electrophoresis, and the part of differentially-expressed proteins were identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS). Results: 6 differentially-expressed proteins were identified between group A and B by MALDI-TOF-MS: tubulin-specific chaperone B, myeloperoxidase, &lt;TT&gt;Solution Structure Of The Ch Domain Of Human Transgelin-2,&lt;/TT&gt; glutathione S-transferase, RING zinc finger protein, glyceraldehyde-3-phosphate dehydrogenase.3 differentially-expressed proteins were identified in group C: NAD(P)H dehydrogenase, hypothetical protein, HES1. Conclusion: The distinct proteins of leukemic cells of AML-M2a patients before inductive treatments were involved in prognosis, and the proteins of BMMNCs from patients at replase have changed.


2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Yiru Shao ◽  
Zhifeng Jiang ◽  
Daikun He ◽  
Jie Shen

Phosgene exposure can cause acute lung injury (ALI), for which there is no currently available effective treatment. Mesenchymal stem cells (MSCs) which have been proven to have therapeutic potential and be helpful in the treatment of various diseases, but the mechanisms underlying the function of MSCs against phosgene-induced ALI are still poorly explored. In this study, we compared the expression profiles of mRNAs, lncRNAs, and circRNAs in the lung tissues from rats of three groups—air control (group A), phosgene-exposed (group B), and phosgene + MSCs (group C). The results showed that 389 mRNAs, 198 lncRNAs, and 56 circRNAs were differently expressed between groups A and B; 130 mRNAs, 107 lncRNAs, and 35 circRNAs between groups A and C; and 41 mRNAs, 88 lncRNAs, and 18 circRNAs between groups B and C. GO and KEGG analyses indicated that the differentially expressed RNAs were mainly involved in signal transduction, immune system processes, and cancers. In addition, we used a database to predict target microRNAs (miRNAs) interacting with circRNAs and the R network software package to construct a circRNA-targeted miRNA gene network map. Our study showed new insights into changes in the RNA expression in ALI, contributing to explore the mechanisms underlying the therapeutic potential of MSCs in phosgene-induced ALI.


2003 ◽  
Vol 104 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Rafael SIMÓ ◽  
Cristina HERNÁNDEZ ◽  
Rosa M. SEGURA ◽  
José GARCÍA-ARUMÍ ◽  
Laura SARAROLS ◽  
...  

The aim of the study was to evaluate the vitreous levels of free insulin-like growth factor 1 (IGF-1) in patients with proliferative diabetic retinopathy (PDR). For this, a total of 36 diabetic patients with PDR (group A) and 28 non-diabetic patients (group B) in whom a vitrectomy was performed were compared. Both groups were matched by age, sex and serum-free IGF-1. In a subgroup of diabetic patients (n = 21) and non-diabetic patients (n = 13), vitreous and serum total IGF-1, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were also determined. Serum and vitreous levels of free IGF-1, total IGF-1, IGFBP-1 and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by a turbidimetric method and adjusted for vitreous haemoglobin. Vitreous levels of free IGF-1 were elevated in group A (median, 0.16ng/ml; range 0.06–0.57ng/ml) in comparison with group B (median, 0.12ng/ml; range 0.06–0.22ng/ml; P<0.001); however, after adjusting for vitreal proteins, free IGF-1 levels were significantly lower in group A in comparison with group B [0.05ng/mg (0.01–0.45ng/mg) versus 0.15ng/mg (0.07–0.66ng/mg); P<0.001]. The relatively lower free IGF-1 level observed in group A could not be attributed to differences in the distribution of intravitreous IGFBP-1 and IGFBP-3 in relation to total IGF-1. Notably, the contribution of free IGF-1 to total IGF-1 in vitreous fluid was 10% in group A and 42% in group B; these percentages largely exceed that obtained in serum (<1%). Our results suggest that although there is an enhancement of intravitreous free IGF-1 in diabetic patients due to serum diffusion, a deficit in its intraocular production also exists. In addition, these findings support the concept that intraocular-produced free IGF-1 plays a relevant role in retinal homoeostasis.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaolu Zhu ◽  
Wen Zeng ◽  
Shengyu Wu ◽  
Xiaomin Chen ◽  
Tian Zheng ◽  
...  

Purpose. To investigate the changes of retinal nerve fiber layer (RNFL) in patients after an attack of primary acute angle closure glaucoma (PAACG) and to assess the impact of attack time on prognosis of retinal changes. Design. cross-sectional study. Methods. Twenty-six patients with unilateral PAACG attack and cataracts from 2017 to 2019 were enrolled. Eyes with PAACG attack time less than 1 day constituted the group A (n = 13), while eyes with PAACG attack time more than 1 day constituted the group B (n = 13). All patients received phacoemulsification and viscogoniosynechialysis after intraocular pressure (IOP) lowering. All patients underwent ophthalmic examinations including IOP, best-corrected visual acuity (BCVA), and visual field (VF). Optical coherence tomography angiography (OCTA) was used to obtain circumpapillary RNFL vessel density (cpVD). Spectral domain optical coherence tomography (SD-OCT) was used to examine the peripapillary RNFL and macular ganglion cell complex (GCC). All patients accepted 2 assessments before and 1 month after the procedure. Results. The IOP of all patients recovered to normal (12.77 ± 2.65 mm Hgvs. 12.77 ± 3.85 mmHg, p=0.834) after the procedure. Patients in the group A had better BCVA improvement than those in the group B (1.32 ± 0.84 vs. 0.50 ± 0.21, p=0.004), as well as better mean defect (MD) values from VF (−3.65 ± 2.54 vs −16.05 ± 5.99, p<0.001). Compared with group B, patients in the group A had thicker macula (Fovea area: 255.00 ± 27.94 μm vs. 203.92 ± 59.73 μm, p=0.010), thicker GCC (82.62 ± 8.76 μm vs. 65.23 ± 18.56 μm, p=0.005), and thicker RNFL (105.08 ± 9.38 μm vs. 77.69 ± 20.23 μm, p<0.001). Higher blood flow density in all-plexus peripapillary retina was observed in the group A eyes compared with group B (full sector: 0.56 ± 0.02 vs. 0.41 ± 0.07, p<0.001). In both groups, the association between average RNFL thickness and cpVD as well as MD values and pattern standard deviation (PSD) values from VF was stronger (R2 = 0.58, 0.60, −0.54, respectively, all p<0.001) than the association between GCC thickness and cpVD, as well as MD values and PSD values (R2 = 0.37, p=0.001; R2 = 0.37, p=0.001; R2 = −0.27, p=0.007). Conclusion. Patients with attack time less than 1 day had better retinal thickness and all-plexus peripapillary retina blood flow density. Controlling the attack time could decrease retinal damage by PAACG.


2016 ◽  
Vol 28 (11) ◽  
pp. 1781 ◽  
Author(s):  
G. L. Cao ◽  
T. Feng ◽  
M. X. Chu ◽  
R. Di ◽  
Y. L. Zhang ◽  
...  

The cost of developing replacement nanny goats could be reduced by decreasing the age at puberty because this way nanny goats could be brought into production at an earlier age. The aim of the present study was to screen genes related to puberty to investigate the molecular mechanisms of puberty. Subtracted cDNA libraries were constructed for hypothalami from juvenile (Group A), pubertal (Group B) and age-matched control pubertal (Group E) Jining grey (JG) and Liaoning cashmere (LC) goats using suppression subtractive hybridisation (SSH). Differentially expressed genes were analysed by bioinformatics methods. There were 203 expressed sequence tags (ESTs) in the subtracted cDNA libraries that were differentially expressed between JG and LC goats at the juvenile stage, 226 that were differentially expressed at puberty and 183 that were differentially expressed in the age-matched control group. The differentially expressed ESTs in each subtracted cDNA library were classified as known gene, known EST and unknown EST according to sequence homology in the GenBank non-redundant (NR) and EST database. According to gene function analysis in the COG (Cluster of Orthologous Groups) database, the known genes were grouped into 10 subdivisions in Group A, into seven subdivisions in Group E and into nine subdivisions in Group B under three categories: cellular processes and signalling, information storage and processing, and metabolism. Pathway analysis in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database of known genes revealed that the three pathways that most differentially expressed genes were involved in were metabolic pathways, Parkinson’s disease and oxidative phosphorylation. Protein interaction analysis of the high homology genes revealed the most dominant network to be structure of ribosome/protein translation, oxidative phosphorylation and carbohydrate metabolism. The results reveal that the onset of puberty is a complex event involving multiple genes in multiple biological processes. The differentially expressed genes include genes related to both neuroendocrine and energy metabolism.


Author(s):  
Danilo Moyses Jorge ◽  
José Edísio da Silva Tavares Neto ◽  
Omero Benedicto Poli-Neto ◽  
Ingrid U. Scott ◽  
Rodrigo Jorge

Abstract Background The main purpose of this study is to compare the vitreous hemorrhage (VH) score reduction and visual acuity outcomes in patients with VH secondary to proliferative diabetic retinopathy (PDR) treated with intravitreal injections of bevacizumab (IVB) versus IVB and pars plana vitrectomy (IVB and PPV). Methods Patients with VH secondary to PDR were randomized into 2 groups: in Group A, patients were treated with a total of 3 IVB (1.5 mg/0.06 ml) at 8-week intervals; and in Group B, patients received a single IVB (1.5 mg/0.06 ml) and, 7 days later, underwent PPV. Patients received an ophthalmic evaluation that included best-corrected visual acuity (BCVA), indirect ophthalmoscopy, and mode B echography at weeks 8, 16 and 24. VH was classified according to the Diabetic Retinopathy Vitrectomy Study classification as grade 1, 2 or 3. Change in VH score was the primary outcome measure and change in BCVA was the secondary outcome. Results Seventy-three eyes of 66 patients were randomized and 70 eyes completed the 24-week follow-up visit. Mean VH score reduction (± SEM) of 0.4571 ± 0.0283 (p = 0.0014), 1.3429 ± 0.0393 (p < 0.0001) and 1.8286 ± 0.0438 (p < 0.001) was observed in Group A at 8, 16 and 24 weeks after treatment, respectively (Table 2; Fig. 2). In Group B, the reduction of VH score (± SEM) was 2.2571 ± 0.0720 (p = 0.0014), 2.2857 ± 0.0606 (p < 0.0001) and 2.2286 ± 0.0726 (p < 0.001) at 8, 16 and 24 weeks after treatment, respectively. Group comparison revealed a significantly greater reduction in mean VH score in Group B at 8 and 16 weeks after treatment (p < 0.0001). However, at 24 weeks this difference was no longer statistically significant (p = 0.1854). In Group A, mean (± SEM) BCVA showed an improvement of 0.00285 ± 0.0004 (p = 0.971), 0.5371 ± 0.0072 (p < 0.0001), 0.8143 ± 0.0001 (p < 0.0001) and 0.8543 ± 0.0008 (p < 0.0001) compared to baseline at 1, 8, 16 and 24 weeks after treatment, respectively. In Group B, mean (± SEM) BCVA showed an improvement of 0.3657 ± 0.0507 (p = 0.0002), 0.8857 ± 0.0385 (p < 0.0001), 0.9457 ± 0.0499 (p < 0.0001) and 0.9629 ± 0477 (p < 0.0001) compared to baseline at 1, 8, 16 and 24 weeks after treatment, respectively. No significant difference in BCVA improvement was observed between groups at 24 weeks after treatment. Conclusion PPV with preoperative IVB is associated with more rapid clearance of VH and improvement in BCVA than IVB injections alone. However, after 24 weeks of follow-up, the reduction in VH score and BCVA were similar between both treatment strategies. Trial Registration The project is registered in Plataforma Brasil with CAAE number 927354.7.0000.5440 and was approved by the Ethics Committee of the Clinics Hospital of Ribeirao Preto Medicine School of São Paulo University—Ribeirão Preto, São Paulo, Brazil (appreciation number 3.053.397 gave the approval).


2019 ◽  
Author(s):  
Zhaodong Du ◽  
Liting Hu ◽  
Wenying Wang ◽  
Lina Zhang ◽  
Qiulu Chen ◽  
...  

Abstract Background: To explore the treatment efficacy of the combination of preoperative intravitreal ranibizumab (IVR) and postoperative intravitreal triamcinolone acetonide (IVTA) in patients undergoing pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). Methods: A retrospective comparative study was performed on 128 eyes of 128 patients who had PDR and underwent PPV. Patients who received a single PPV were assigned to Group A. Those who received PPV with preoperative IVR were assigned to Group B. Patients in Group C underwent PPV combined preoperative IVR and postoperative IVTA. Intraoperative findings, changes in mean best-corrected visual acuity (BCVA) and postoperative adverse events were retrospectively evaluated at 6-month follow-up. Results: The incidences of iatrogenic breaks, severe intraoperative bleeding, using long-term internal tamponade agents, recurrent vitreous hemorrhage (VH) and duration of surgery were statistically significantly less in Group B and Group C than in Group A. The postoperative BCVA was statistically significantly better in Groups B and Group C than in Group A respectively at 1 month after surgery. The mean 3-month postoperative visual acuity was better in Group C. The incidence of high intraocular pressure (IOP) was significantly higher in Group C at the first postoperative week. There were no statistically significant differences in the incidence of exudative retinal detachment and choroidal detachment among the three groups. Conclusion: In patients undergoing PPV for PDR, preoperative IVR significantly reduced the occurrence of intraoperative and postoperative complications, and the combination of preoperative IVR and postoperative IVTA can better improve the postoperative visual outcome.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chen Zou ◽  
Minjie Zhao ◽  
Jingjing Yu ◽  
Dandan Zhu ◽  
Yunzhi Wang ◽  
...  

Purpose. To examine the difference in the vitreal protein profiles of patients with proliferative diabetic retinopathy (PDR) with and without preoperative intravitreal conbercept (IVC) treatment. Methods. Liquid chromatography-tandem mass spectrometry- (LC-MS/MS-) based proteomic methods were used to determine the protein profiles of the vitreous humor in patients with PDR treated with (IVC group; n=9) and without (PDR group; n=8) preoperative IVC. Gene ontology (GO) annotation and REACTOME pathway analysis were obtained to overview differentially expressed proteins between each group. Intravitreal levels of apolipoprotein A-II (APOA2) and ceruloplasmin (CP) were measured using enzyme-linked immunosorbent assays. Results. 307 proteins were expressed differentially between PDR and IVC groups, including 218 proteins downregulated in response to IVC. The most notable GO annotations in level 3 and REACTOME pathways describing the differentially expressed proteins were “innate immune response” and “platelet degranulation.” The intravitreal levels of APOA2 and CP were lower in the IVC group than in the PDR group (p<0.01). Conclusions. In addition to decreasing the intravitreal vascular endothelial growth factor level, IVC may alter the vitreal protein profile in patients with PDR, with the differentially regulated proteins involved in the immune response, platelet degranulation, complement activation, and inflammation.


2018 ◽  
Vol 24 (27) ◽  
pp. 3276-3281 ◽  
Author(s):  
Dorota Raczyńska ◽  
Katarzyna A. Lisowska ◽  
Krzysztof Pietruczuk ◽  
Joanna Borucka ◽  
Mateusz Ślizień ◽  
...  

Objective: The objective of the study was to compare cytokine levels in the vitreous body of patients with proliferative diabetic retinopathy (PDR) undergoing posterior vitrectomy. Patients and methods: The study included 39 patients (39 eyes) undergoing pars plana vitrectomy (PPV). Patients were divided into three groups: patients with proliferative diabetic retinopathy (PDR) without aflibercept injection prior to the surgery, PDR patients administered aflibercept injection prior to the surgery, and patients without diabetes mellitus (control group). All patients underwent a comprehensive eye examination one day before and 3 weeks after the surgery, including measurements of: best-corrected visual acuity (BVCA) and intraocular pressure (IOP), slit-lamp examination and spectral domain optical coherence tomography (SOCT). Concentrations of cytokines: IL-6, IL-8, IL-12p70, TNF, IL-10, IL-1β were measured in the vitreous body of patients with BD™ Cytometric Bead Array (CBA) Human Inflammatory Cytokines Kit. Results: PDR patients who received pretreatment with aflibercept injection showed significantly lower concentrations of IL-12p70, TNF, IL-10 and IL-1β in the vitreous body compared to the control group. Meanwhile, patients without prior aflibercept injection had a significantly higher concentration of IL-8. There was also a significant positive correlation between IOP before PPV and IL-8 concentration in both PDR patients’ groups. Conclusion: Findings of our study suggest an important role of IL-8 in the development of severe PDR. Aflibercept administration on the day before elective vitrectomy facilitated the surgery.


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