scholarly journals C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function

2017 ◽  
Vol 312 (3) ◽  
pp. C244-C253 ◽  
Author(s):  
Blanca Molins ◽  
Anna Pascual ◽  
Méndez ◽  
Victor Llorenç ◽  
Javier Zarranz-Ventura ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Protein Isoforms ◽  
Age Related Macular Degeneration ◽  
C Reactive Protein ◽  
Barrier Dysfunction ◽  
Blood Retinal Barrier ◽  
Reactive Protein ◽  
Anti Vegf ◽  
Age Related

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier (oBRB) and is the prime target of early age-related macular degeneration (AMD). C-reactive protein (CRP), a serum biomarker for chronic inflammation and AMD, presents two different isoforms, monomeric (mCRP) and pentameric (pCRP), that may have a different effect on inflammation and barrier function in the RPE. The results reported in this study suggest that mCRP but not pCRP impairs RPE functionality by increasing paracellular permeability and disrupting the tight junction proteins ZO-1 and occludin in RPE cells. Additionally, we evaluated the effect of drugs commonly used in clinical settings on mCRP-induced barrier dysfunction. We found that a corticosteroid (methylprednisolone) and an anti-VEGF agent (bevacizumab) prevented mCRP-induced ARPE-19 barrier disruption and IL-8 production. Furthermore, bevacizumab was also able to revert mCRP-induced IL-8 increase after mCRP stimulation. In conclusion, the presence of mCRP within retinal tissue may lead to disruption of the oBRB, an effect that may be modified in the presence of corticosteroids or anti-VEGF drugs.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals LRG1 Expression Is Elevated in the Eyes of Patients with Neovascular Age-Related Macular Degeneration

2021 ◽  
Vol 22 (16) ◽  
pp. 8879
Author(s):  
Lucia Mundo ◽  
Gian Marco Tosi ◽  
Stefano Lazzi ◽  
Grazia Pertile ◽  
Barbara Parolini ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Aqueous Humor ◽  
Smooth Muscle Actin ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Average Concentration ◽  
Age Related Macular Degeneration ◽  
Surrounding Tissue ◽  
Anti Vegf ◽  
Age Related

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.

scholarly journals Oxidative stress-mediated TXNIP loss causes RPE dysfunction

2019 ◽  
Vol 51 (10) ◽  
pp. 1-13 ◽  
Author(s):  
Min Ji Cho ◽  
Sung-Jin Yoon ◽  
Wooil Kim ◽  
Jongjin Park ◽  
Jangwook Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Common Factor ◽  
Age Related Macular Degeneration ◽  
Autophagic Flux ◽  
Blood Retinal Barrier ◽  
Rpe Cells ◽  
Age Related

Abstract The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood–retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1α, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD.

scholarly journals Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring

2015 ◽  
Vol 235 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Christoph R. Clemens ◽  
Nicole Eter
Keyword(s):  
Retinal Pigment Epithelium ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Therapeutic Monitoring ◽  
Temporal Association ◽  
Anti Vegf ◽  
Age Related ◽  
Rpe Tear

Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularised RPE detachment due to age-related macular degeneration (AMD), and they usually involve a deleterious loss in visual acuity. Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies as well as a temporal association between the tear event and the intravitreal injection. As the number of AMD patients and the number of administered anti-VEGF injections increase, both the challenge of RPE tear prevention and the treatment after RPE tear formation have become more important. At the same time, the evolution of retinal imaging has significantly contributed to a better understanding of RPE tear development in recent years. This review summarises the current knowledge on RPE tear development, predictive factors, and treatment strategies before and after RPE tear formation.

Retinal Pigment Epithelium Tears After Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration

2021 ◽  
Author(s):  
Jayoung Ahn ◽  
Daniel Duck-Jin Hwang ◽  
Joon Hong Sohn ◽  
Gisung Son
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Visual Acuity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor ◽  
Rpe Tear

Purpose: To assess the visual prognostic factors of retinal pigment epithelium (RPE) tears and describe their clinical features. Methods: The medical records of treatment-naive neovascular age-related macular degeneration patients who received intravitreal anti-vascular endothelial growth factor (VEGF) injections were retrospectively reviewed. Results: The incidence of RPE tears was 1.36% (10 out of 733 eyes). The type of anti-VEGF agent administered did not affect the incidence (p = 0.985). The median best-corrected visual acuity (BCVA) of 10 patients decreased after an RPE tear (0.4 to 0.6 logMAR); however, subsequent injections restored the BCVA to a level similar to that before the RPE tear (0.4 logMAR, p = 0.436). Central macular thickness improved significantly during the study (794.4 to 491.9 μm, p = 0.013). The final BCVA was positively correlated with the BCVA before and immediately after the RPE tear (p = 0.025 and 0.002, respectively) and was weakly correlated with foveal involvement of the RPE tear (p = 0.061). Conclusion: The incidence of RPE tears did not differ according to the type of anti-VEGF agent. The final BCVA was proportional to the BCVA before and after RPE tears. Continuous treatment with anti-VEGF after the occurrence of RPE tears can benefit the final visual acuity and macular anatomy.

scholarly journals Incidence of Retinal Pigment Epithelial Tears and Associated Risk Factors After Treatment of Age-Related Macular Degeneration with Intravitreal Anti-VEGF Injections§

2014 ◽  
Vol 8 (1) ◽  
pp. 101-104 ◽  
Author(s):  
Theodoros Empeslidis ◽  
Athanasios Vardarinos ◽  
Vasileios Konidaris ◽  
Soon Wai Ch'ng ◽  
Bharat Kapoor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Associated Risk Factors ◽  
Rpe Tear

Purpose : To study the incidence and risk factors for retinal pigment epithelium tears following intravitreal anti-vascular endothelial growth factor (VEGF) injections. Methods : Retrospective longitudinal study. 4027 intravitreal anti-VEGF injections in 628 patients (676 eyes) for choroidal neovascularisation associated with age related macular degeneration in a period of 18 months were studied. Results : Seventeen patients (mean age 83.95±5.84) developed retinal pigment epithelium tears. The incidence rate was 0.4%. Fibrovascular pigment epithelium detachment (PED) was previously observed in all cases. In 88 % (15/17) of AMD patients that had a RPE tear, PED height was found to be less than 400 microns at presentation. In 5 of 7 patients with RPE tear grade <4, continuing of anti-VEGF treatment resulted to improvement of visual acuity. Conclusion : Critical risk factors for RPE tears are presence of PED as well as advanced age. Visual improvement appears to depend more on the extent and location of the RPE tear and less on the PED height.

Nutraceutical «Resvega Forte» in complex treatment of neovascular age-related macular degeneration against the background of anti-VEGF therapy

2021 ◽  
pp. 312-316
Author(s):  
L.P. Danilova ◽  
◽  
V.V. Egorov ◽  
G.P. Smoliakova ◽  
D.А. Povalyaeva ◽  
...  
Keyword(s):  
Disease Activity ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Angiogenesis Inhibitor ◽  
Age Related Macular Degeneration ◽  
Morphological Parameters ◽  
Complex Treatment ◽  
Anti Vegf ◽  
Age Related

Purpose. To evaluate clinical efficacy of using nutraceutical "Resvega Forte" in complex treatment neovascular age-related macular degeneration (nAMD) against the background anti-VEGF therapy using ranibizumab (LUCENTIS®). Material and methods. The object of the study was 30 patients (30 eyes) with nAMD, who received 3 "loading" intravitreal injections (IVI) of 0,5 mg (0,05 ml) ranibizumab at intervals of 1 time per month, then within a year – by the protocol "Tread-and-Extend" with increase interval between injections by 2 weeks in the absence of disease activity and its reduction in case of resumption of activity. Patients of the 1st group (16 people) were supplemented with 3 "loading" IVI of ranibizumab with appointment of "Resvega Forte" complex for 3 months and then after 6 months. Patients of the 2nd group (14 people) did not receive "Resvega Forte" complex. To assess the effectiveness of treatment, in addition to standard methods, optical coherence tomography was performed with assessment of the central retinal thickness (CRT), the presence of detachment of the retinal pigment epithelium (RPE), retinal neuroepithelium (RNE), sub- and intraretinal fluid under PE. Results. By the 12th month of observation, none of the patients of the 1st group against the background of using two complexes "Resvega Forte" was found to have resumption of disease activity: the BCVA increased 3 times and amounted to 0,78±0,04, the average indexes of CRT corresponded to the norm (249,5±12,1 µm). The interval between injections increased to 12 weeks, and their total number was 7. In the 2nd group, the resumption of disease activity was noted twice, which was accompanied by decrease in the functional and morphological parameters of retina and required decrease in the intervals between injections to 10 weeks, which accordingly led to an increase in their number to 9-10. Conclusion. The inclusion of nutraceutical "Resvega Forte" in the treatment regimen of nAMD against the background of the therapy using angiogenesis inhibitor LUCENTIS® in the protocol "Tread-and-Extend" mode allows to reduce the risk of progression of nAMD, as well as to improve the functional and morphological parameters of retina. An integrated approach makes it possible to increase the interval between injections and reduce additional monitoring, which reduces the burden on both the patient and the doctor. Key words: neovascular age-related macular degeneration, aflibercept, nutraceuticals, "Resvega forte".

scholarly journals Progression of Retinal Pigment Epithelium Atrophy in Patients with Long-Term Anti-Vegf Treatment for Exudative Age-Related Macular Degeneration

2017 ◽  
Vol 17 (2) ◽  
pp. 9-13
Author(s):  
Lita Jekabsone ◽  
Anete Kursite ◽  
Oskars Gertners ◽  
Guna Laganovska
Keyword(s):  
Visual Acuity ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
First Year ◽  
Anti Vegf ◽  
Age Related ◽  
Retinal Pigment Epithelium Atrophy

Abstract Introduction.Age-related macular degeneration is the leading cause of visual impairment in developed world. The reason for using intravitreal injections of anti-vascular endothelial growth factor (VEGF) is to prevent choroidal neovascularization which is the main pathogenic mechanism for exudative age-related macular degeneration. Although injections may improve visual acuity, there are evidence showing association of anti-VEGF injections with progression of retinal pigment epithelium (RPE) atrophy. Aim of the Study.The purpose of this study was to investigate the intravitreal anti-vascular endothelial growth factor impact on retinal pigment epithelium atrophy development and progression. Material and methods.A single-centre retrospective study was conducted. Total 51 eyes of 39 patients with exudative age-related macular degeneration undergoing intravitreal anti-vascular endothelial growth factor therapy for 48 months. Heidelberg Spectralis Optical Coherence Tomography and fundus autofluorescence were used for evaluation of retinal pigment epithelium atrophy area and retinal thickness. Measurements were made manually. Best-corrected visual acuity (BCVA) measurements were taken from patient medical histories. For statistical analysis, IBM Statistical Package for the Social Sciences, version 23.0 was used. Results.The average age of patients was 81.6 ± 6.7 years. After first year of intravitreal anti-VEGF therapy, retinal pigment epithelium atrophy area enlarged from baseline (from 1.91 ± 2.3 mm2 to 2.74 ± 2.3mm2, p < 0.001). The mean number of intravitreal anti- VEGF injections received in 48 months was 15.47 ± 5.14. There was a statistically significant correlation between total number of intravitreal injections and RPE atrophy (R = 0.757, p < 0.001). After first year of anti-VEGF therapy best-corrected visual acuity (decimals) was statistically improved from baseline (0.32 ± 0.26 to 0.37 ± 0.24, p = 0.04). However, despite significant improvement at first year, the further treatment contributed BCVA reduction. Conclusions.Retinal pigment epithelium atrophy is a frequent finding in eyes with exudative age-related macular degeneration before and after anti-VEGF therapy. Our data show statistically significant association between total number of intravitreal anti-VEGF injections and retinal pigment epithelium atrophy area enlargement. Also there was statistically significant best-corrected visual acuity improvement after first year of anti-VEGF therapy.

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