Prevention of Age-Related Macular Degeneration

Singh, Niharika; Srinivasan, Sangeetha; Muralidharan, Vinata; Roy, Rupak; Jayprakash,; Raman, Rajiv

doi:10.22608/apo.2017416

Cited by 9 publications

(2 citation statements)

References 72 publications

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“…Following the invention of bevacizumab, a variety of VEGF-VEGFR targeted agents come out. Apart from anti-VEGF mAb, there are other three approaches to inhibit VEGF-VEGFR signaling pathway: (I) decoy VEGF-trap receptor such as aflibercept [46]; (II) anti-VEGFR2 mAb such as ramucirumab [47]; (III) tyrosine kinase inhibitor (TKI) which interferes intracellular signal transduction of VEGF such as axitinib, sorafenib, sunitinib, and vatalanib [48–51]. Moreover, based on chimeric antigen receptor (CAR) T cell technology, Chinnasamy et al developed anti-VEGFR2 CAR T cell to retard tumor growth [52].…”

Section: Anti-angiogenesis Agents: the Natural Ally Of Icimentioning

confidence: 99%

Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment

et al. 2019

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Immune checkpoint inhibitor (ICI) activates host’s anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. In clinical practice, a main concerning for choosing ICI is the low response rate. Even though multiple predictive biomarkers such as PD-L1 expression, mismatch-repair deficiency, and status of tumor infiltrating lymphocytes have been adopted for patient selection, frequent resistance to ICI monotherapy has not been completely resolved. However, some recent studies indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment. Actually, anti-angiogenesis therapy not only prunes blood vessel which is essential to cancer growth and metastasis, but also reprograms the tumor immune microenvironment. Preclinical studies demonstrated that the efficacy of combination therapy of ICI and anti-angiogenesis was superior to monotherapy. In mice model, combination therapy could effectively increase the ratio of anti-tumor/pro-tumor immune cell and decrease the expression of multiple immune checkpoints more than PD-1. Based on exciting results from preclinical studies, many clinical trials were deployed to investigate the synergistic effect of the combination therapy and acquired promising outcome. This review summarized the latest understanding of ICI combined anti-angiogenesis therapy and highlighted the advances of relevant clinical trials.

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Section: Anti-angiogenesis Agents: the Natural Ally Of Icimentioning

confidence: 99%

Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment

et al. 2019

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“…We modified a quantitative Food Frequency Questionnaire (FFQ) to assess the intake of the following food groups rich in nutrients considered important in the AMD aetiology and oxidative processes to evaluate the participants’ dietary habits: fatty fish, eggs, green vegetables, fruit and fruit juice, omega-3-rich oils, simple and complex carbohydrates, as recommended previously [ 11 , 13 , 33 , 34 ]. Three different frequencies in terms of portions per week were available for selection for each food type and alcoholic drink as follows: fatty fish: <1, 2–4, and >4; eggs: <1, 2–4, and >4; green vegetables: <2, 2–7, and >7; fruit and fruit juice: <2, 2–7, and >7; omega-3-rich oils: <2, 2–7, and >7; simple carbohydrates: <2, 2–7, and >7; complex carbohydrates: <2, 2–7, and >7; beer: 0, ≤1, and 2–7; wine: 0, <2, and 2–7; and vodka: 0, ≤1, and 2–3.…”

Section: Methodsmentioning

confidence: 99%

Dietary and Lifestyle Factors Modulate the Activity of the Endogenous Antioxidant System in Patients with Age-Related Macular Degeneration: Correlations with Disease Severity

et al. 2020

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Age-related macular degeneration (AMD) is a common cause of blindness in the elderly population, but the pathogenesis of this disease remains largely unknown. Since oxidative stress is suggested to play a major role in AMD, we aimed to assess the activity levels of components of the antioxidant system in patients with AMD. We also investigated whether lifestyle and dietary factors modulate the activity of these endogenous antioxidants and clinical parameters of disease severity. We recruited 330 patients with AMD (39 with early, 100 with intermediate and 191 with late form of AMD) and 121 controls in this study. At enrolment, patients’ dietary habits and physical activity were assessed, and each study participant underwent a thorough ophthalmologic examination. The activity of several components of the antioxidant system were measured in red blood cells and platelets using both kinetic and spectrophotometric methods. Patients with AMD consumed much lower levels of fatty fish and eggs than the control group (p = 0.008 and p = 0.04, respectively). In the nAMD group, visual acuity (VA) correlated positively with green vegetable consumption (Rs = +0.24, p = 0.004) and omega-3-rich oil intake (Rs = +0.17, p = 0.03). In the AMD group, the total physical activity MET score correlated positively with VA (Rs = +0.17, p = 0.003) and correlated negatively with the severity of AMD (Rs = −0.14, p = 0.01). A multivariate analysis of patients and controls adjusted for age, sex, and smoking status (pack-years) revealed that AMD was an independent variable associated with a lower RBC catalase (β = −0.37, p < 0.001) and higher PLT catalase (β = +0.25, p < 0.001), RBC GPx (β = +0.26, p < 0.001), PLT GPx (β = +0.16, p = 0.001), RBC R-GSSG (β = +0.13, p = 0.009), PLT R-GSSG (β = +0.12, p = 0.02) and RBC GSH transferase (β = +0.23, p < 0.001) activity. The activities of components of the antioxidant system were associated with disease severity and depended on dietary habits. The observed substantial increase in the activity of many critical endogenous antioxidants in patients with AMD further indicates that the required equilibrium in the antioxidant system is disturbed throughout the course of the disease. Our findings explicitly show that a diet rich in green vegetables, fish and omega-3-rich oils, supplemented by physical exercise, is beneficial for patients with AMD, as it might delay disease progression and help retain better visual function.

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Farrerol Enhances Nrf2‐Mediated Defense Mechanisms against Hydrogen Peroxide‐Induced Oxidative Damage in Human Retinal Pigment Epithelial Cells by Activating Akt and MAPK

Yang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Oxidative stress of the retinal pigment epithelium (RPE) is an essential element contributing to the progression of age-related macular degeneration (AMD). Notably, the activation of Nrf2 is regarded as an effective strategy for controlling oxidation. The novel 2,3-dihydroflavonoid compound farrerol, which is extracted from Rhododendron, possesses antioxidant properties. In this study, we investigated the mechanism by which farrerol protects against oxidative damage mediated by hydrogen peroxide (H2O2) in adult retinal pigment epithelial cell line 19 (ARPE-19) cells. Farrerol supplementation conspicuously reversed H2O2-related cell damage through declining the generation of intracellular reactive oxygen species (ROS) and MDA and increasing the concentrations of GSH and SOD. According to the results of the apoptosis assay, a farrerol pretreatment decreased the protein expression of the Bax/Bcl-2, cleaved caspase-3, PARP, caspase-8, and caspase-9 proteins. Furthermore, farrerol markedly activated Nrf2, thereby increasing the levels of antioxidant enzymes downstream of Nrf2, such as HO-1, NQO1, and GCLM. Knockdown of Nrf2 with a specific siRNA successfully suppressed farrerol-mediated HO-1 transcription and partially abolished the cytoprotective effect on ARPE-19 cells. Meanwhile, farrerol induced Akt and MAPK phosphorylation in a dose-related way. However, inhibiting Akt and MAPK substantially blocked the cytoprotective functions of farrerol. Therefore, farrerol enhanced Nrf2-mediated cytoprotection of oxidative damage caused by H2O2, which may be inseparable from the activation of Akt and MAPK.

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Prevention of Age-Related Macular Degeneration

Cited by 9 publications

References 72 publications

Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment

Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment

Dietary and Lifestyle Factors Modulate the Activity of the Endogenous Antioxidant System in Patients with Age-Related Macular Degeneration: Correlations with Disease Severity

Farrerol Enhances Nrf2‐Mediated Defense Mechanisms against Hydrogen Peroxide‐Induced Oxidative Damage in Human Retinal Pigment Epithelial Cells by Activating Akt and MAPK

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