scholarly journals Differences in the Quantity and Composition of Extracellular Vesicles in the Aqueous Humor of Patients with RetinalNeovascular Diseases

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1276
Author(s):  
Yai-Ping Hsiao ◽  
Connie Chen ◽  
Chee-Ming Lee ◽  
Pei-Ying Chen ◽  
Wei-Heng Chung ◽  
...  

Extracellular vesicles (EVs) are secreted by various cells in the body fluid system and have been found to influence vessel formation and inflammatory responses in a variety of diseases. However, which EVs and their subtypes are involved in vascular retinal diseases is still unclear. Therefore, the aim of this study was to explore the particle distribution of EVs in retinal neovascular diseases, including age-related macular degeneration, polypoidal choroidal vasculopathy, and central retinal vein occlusion. The aqueous humor was harvested from 20 patients with different retinal neovascular diseases and six patients with cataracts as the control group. The particle distribution was analyzed using nanoparticle tracking analysis (NTA) and transmitting electron microscopy (TEM). The results revealed that the disease groups had large amounts of EVs and their subtypes compared to the control group. After isolating exosomes, a higher expression of CD81+ exosomes was shown in the disease groups using flow cytometry. The exosomes were then further classified into three subtypes of exomeres, small exosomes, and large exosomes, and their amounts were shown to differ depending on the disease type. To the best of our knowledge, this is the first study to elucidate the dynamics of EVs in retinal neovascular diseases using clinical cases. Our findings demonstrated the possible functionality of microvesicles and exosomes, indicating the potential of exosomes in the diagnosis and therapy of retinal neovascular diseases.

2021 ◽  
Vol 15 (1) ◽  
pp. 209-216
Author(s):  
Ryosuke Motohashi ◽  
Hidetaka Noma ◽  
Kanako Yasuda ◽  
Yuko Kasezawa ◽  
Hiroshi Goto ◽  
...  

Purpose: The role of inflammation and cytokines in AMD and anti-Vascular Endothelial Growth Factor (anti-VEGF) treatment remains unclear. Therefore, this study aimed to examine whether anti-VEGF treatment for exudative Age-related Macular Degeneration (AMD) affects aqueous flare value (an indicator of inflammation), functional-morphologic parameters, and aqueous humor levels of cytokines or inflammatory mediators. Methods: We compared aqueous humor levels of 8 cytokines, growth factors (including VEGF), and inflammatory mediators in 43 patients who received anti-VEGF treatment with aflibercept for AMD and 24 healthy controls by the suspension array method. In addition, we measured aqueous flare values with a laser flare meter and Central Macular Thickness (CMT) and Macular Volume (MV) by optical coherence tomography. Results: The patient group had a significantly higher aqueous flare value than the control group. At baseline, CMT showed significant correlations with aqueous humor levels of soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, and IL-8 and MV, with aqueous humor levels of VEGF, sICAM-1, MCP-1, IL-6, and IL-8. Moreover, we found significant correlations between aqueous flare value and aqueous humor levels of MCP-1, IL-6, IL-8, and interferon-gamma–inducible protein 10. One month after anti-VEGF treatment, the patient group showed a significant correlation between the change in MV and improvement in best-corrected visual acuity (BCVA); CMT showed no such correlation. Conclusion: Inflammation appears to be involved in AMD. Change in MV may be an index of improvement in BCVA in patients receiving anti-VEGF treatment for AMD.


2019 ◽  
Author(s):  
Huiying Zhou ◽  
Yinyu Zhao ◽  
Mingzhen Yuan ◽  
Youxin Chen

Abstract Background The concentrations of cytokines in the aqueous humor from neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) may vary. The study was conducted to compare various cytokine levels in the aqueous humor of eyes with PCV, nAMD and control.Methods The present case control study included 49 treatment-naïve eyes from 49 patients (PCV 24, nAMD 11, and cataract 14 eyes). Totally 34 angiogenic and inflammatory cytokines in the aqueous humor were measured by Luminex bead-based multiplex array.Results The aqueous humor levels of IL-8 and IL-12p70 in the nAMD group were significantly higher than the PCV group (p=0.031, p=0.012, respectively). The levels of IL-8, IL-18, IL-21, IL-31, LIF, SDF1-α, FGF-basic, VEGF-A, and VEGF-D in the aqueous humor were significantly higher in the nAMD group and PCV group than the control (nAMD vs control, p=0.004, 0.002, 0.005, <0.0001, <0.0001, <0.0001, 0.023, <0.0001, <0.0001, respectively, PCV vs control, p=0.031, <0.0001, <0.0001, <0.0001, <0.0001, <0.0001, 0.026, <0.0001, <0.0001, respectively). In contrast, the levels of BDNF, HGF, IP-10, MCP-1, and IL-13 in the aqueous humor were significantly lower in the nAMD group and PCV group than control (nAMD vs control, p=<0.0001, <0.0001, 0.003, <0.0001, <0.0001, respectively, PCV vs control, p=<0.0001, <0.0001, <0.0001, <0.0001, <0.0001, respectively). There were significant correlations among nAMD group, PCV group and control group in aqueous humor levels of HGF, IP-10, MCP-1, IL-13, IL-31, LIF, SDF1-α, VEGF-A, VEGF-D by multivariate logistic analysis.Conclusions Various cytokines involved in inflammation and angiogenesis including HGF, IP-10, MCP-1, IL-13, IL-31, LIF, SDF1-α, VEGF-A and VEGF-D may contribute to the pathogenesis of nAMD and PCV. Measurement of IL-8 and IL-12p70 in the aqueous humor may help to differentiate nAMD and PCV.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elżbieta Krytkowska ◽  
Aleksandra Grabowicz ◽  
Katarzyna Mozolewska-Piotrowska ◽  
Zofia Ulańczyk ◽  
Krzysztof Safranow ◽  
...  

AbstractDisturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β =  + 0.18, p = 0.0007, β =  + 0.18, p = 0.0008, respectively) and to dry AMD (β =  + 0.17, p = 0.00003 for both ATC and AVC and β =  − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs =  − 0.13, p < 0.05; Rs =  − 0.12; p < 0.05, Rs =  − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs =  − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.


2017 ◽  
Vol 89 ◽  
pp. 163 ◽  
Author(s):  
Michael Kirschfink ◽  
Tina Schick ◽  
Marlin Steinhauer ◽  
Alexander Aslanidis ◽  
Lebriz Altay ◽  
...  

Author(s):  
Luciano Mesquite Simmo ◽  
Carissa Fouad Ibrahim ◽  
Senice Alvarenga Rodrigues Silva ◽  
Thai Nunes Andrade ◽  
Doora Faleiros Leite ◽  
...  

Objective: To compare the vision-targeted health related quality of life (HRQOL) between neuro-ophthalmological patients and other eye diseases by the National Eye Institute 25-Item Visual Function Questionnaire. Methods: Cross sectional study with a control group and patients with the following pathologies: primary open-angle glaucoma (POAG), diabetic retinopathy (DR), age-related macular degeneration (ARMD), non-arteritic ischemic optic neuropathy (NAION), intracranial hypertension (IH), optic neuritis (ON), ptosis and cataract. Results: All comparisons of the subscales scores among the control group and the patient groups were statistically significant (p<0.05) except for “ocular pain” (p=0.160), “social functioning” (p=0.052) and “peripheral vision” (p=0.112). The control group had the best scores across all dimensions of the NEI VFQ-25. Interestingly, the ARMD and cataract groups presented the best and worst total scores of NEI VFQ-25, respectively. The lowest subscales scores were found in the cataract, in the NAION/ON, and in the POAG groups. Finally, the comparison between the NAION/ON/IH patients and the other eye diseases did not show statistical significance in any subscale. Conclusion: The NEI VFQ-25 showed the impact of various eye conditions in vision-targeted HRQOL, and no difference was measured between neuro-ophthalmological patients and other eye diseases


2018 ◽  
Vol 11 (4) ◽  
pp. 112 ◽  
Author(s):  
Wanting Shu ◽  
Joshua Dunaief

Iron is essential for life, while excess iron can be toxic. Iron generates hydroxyl radical, which is the most reactive free radical, causing oxidative stress. Since iron is absorbed through the diet but not excreted from the body, it accumulates with age in tissues, including the retina, consequently leading to age-related toxicity. This accumulation is further promoted by inflammation. Hereditary diseases such as aceruloplasminemia, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, and posterior column ataxia with retinitis pigmentosa involve retinal degeneration associated with iron dysregulation. In addition to hereditary causes, dietary or parenteral iron supplementation has been recently reported to elevate iron levels in the retinal pigment epithelium (RPE) and promote retinal degeneration. Ocular siderosis from intraocular foreign bodies or subretinal hemorrhage can also lead to retinopathy. Evidence from mice and humans suggests that iron toxicity may contribute to age-related macular degeneration pathogenesis. Iron chelators can protect photoreceptors and RPE in various mouse models. The therapeutic potential for iron chelators is under investigation.


2021 ◽  
Vol 22 (16) ◽  
pp. 8879
Author(s):  
Lucia Mundo ◽  
Gian Marco Tosi ◽  
Stefano Lazzi ◽  
Grazia Pertile ◽  
Barbara Parolini ◽  
...  

Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium–choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.


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