Wnt Modulators in the Aqueous Humor Are Associated With Outer Retinal Damage Severity in Patients With Neovascular Age-Related Macular Degeneration

2014 ◽  
Vol 55 (9) ◽  
pp. 5522 ◽  
Author(s):  
Kyu Hyung Park ◽  
Ae Jin Choi ◽  
Jeehyun Yoon ◽  
Daehan Lim ◽  
Se Joon Woo ◽  
...  
2017 ◽  
Vol 89 ◽  
pp. 163 ◽  
Author(s):  
Michael Kirschfink ◽  
Tina Schick ◽  
Marlin Steinhauer ◽  
Alexander Aslanidis ◽  
Lebriz Altay ◽  
...  

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.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Huiying Zhou ◽  
Xinyu 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 After adjusting for gender and age by multivariate logistic analysis, concentrations of IL-31, LIF, SDF1-α, VEGF-A, VEGF-D were significantly higher in eyes with nAMD or PCV compared with control eyes (all P < 0.05, times in nAMD: 59.5, 6.0, 7.0, 4.5, 5.6, respectively, times in PCV: 51.9, 5.21, 6.6, 4.0, 5.1, respectively), and concentrations of HGF, IP-10, MCP-1, IL-13 were significantly lower in eyes with nAMD or PCV than in control eyes (all P < 0.05, times in nAMD: 2.6, 2.0, 4.5, 4.7, respectively, times in PCV: 1.9, 3.0, 3.0, 2.8, respectively), but none of the 34 cytokines, including VEGF and IL-8, showed significantly different between eyes with nAMD and PCV. Conclusions Various cytokines involved in inflammation and angiogenesis including elevated IL-31, LIF, SDF1-α, VEGF-A, VEGF-D might be involved in the pathogenesis of nAMD or PCV. None of the 34 cytokines may help to differentiate nAMD and PCV.


2020 ◽  
Author(s):  
Joshua A. Chu-Tan ◽  
Zhi-Ping Feng ◽  
Yvette Wooff ◽  
Adrian V. Cioanca ◽  
Ulrike Schumann ◽  
...  

SummaryMicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases, including age-related macular degeneration, acting as post-transcriptional gene suppressors through their association with argonaute (AGO) protein family members. However, to understand their role in disease, investigation into the regulatory nature of miRNA with their targets is required. To identify the active-miRnome-targetome interactions in the degenerating retina, AGO2 HITS-CLIP was performed using a mouse model of retinal degeneration. Analysis revealed a similar miRnome between healthy and damaged retinas, however, a shift in the active targetome was observed. This shift was also demonstrated by a change in the seed binding regions of miR-124-3p, the most abundant retinal miRNA loaded in AGO2. Following damage, AGO2 was localised to the inner retinal layers indicating a locational miRNA response to retinal damage. This study provides important insight into the alteration of miRNA regulatory activity that occurs as a response to retinal degeneration.


2021 ◽  
Vol 15 (1) ◽  
pp. 187-195
Author(s):  
Tatsuya Mimura ◽  
Hideharu Funatsu ◽  
Hidetaka Noma ◽  
Aki Kondo ◽  
Atsushi Mizota

Purpose: The purpose of this study is to compare the aqueous humor level of Silent Information Regulator T1 (SIRT1) between patients with Age-related Macular Degeneration (AMD) and cataract patients. Materials and Methods: Aqueous humor level of SIRT1 was measured by enzyme-linked immunosorbent assay in 13 patients with wet-type AMD (n=13, AMD group) and 13 patients with cataracts (cataract group). In addition, the thickness of each retinal layer was determined by optical coherence tomography. Results: The aqueous humor level of SIRT1 was significantly lower in the AMD group than in the cataract group (p=0.007). In the AMD group, the SIRT1 level was positively correlated with the thickness of the retinal ganglion cell layer (r=0.31) and the inner nuclear layer (r=0.76). Conclusion: The aqueous level of SIRT1 decreased as the ganglion cell layer and inner nuclear layer became thinner, suggesting that reduction of SIRT1 activity might be involved in the pathogenesis of this disease.


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