scholarly journals Protective effects of PARP1-inhibitory compound in dry age-related macular degeneration

2021 ◽  
Vol 133 ◽  
pp. 111041
Author(s):  
Jeongmin Ho ◽  
Ki-Hong Jang ◽  
Tae-Sung Koo ◽  
Changmin Park ◽  
Young-Hoon Kim ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Age Related ◽  
Inhibitory Compound

scholarly journals Protective Effects of Curcumin Ester Prodrug, Curcumin Diethyl Disuccinate against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells: Potential Therapeutic Avenues for Age-Related Macular Degeneration

2019 ◽  
Vol 20 (13) ◽  
pp. 3367 ◽  
Author(s):  
Chawanphat Muangnoi ◽  
Umar Sharif ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Pornchai Rojsitthisak ◽  
Luminita Paraoan
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Parent Drug ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Rpe Cells ◽  
Age Related ◽  
Potent Drug

Oxidative stress-induced damage to the retinal pigmented epithelium (RPE), a specialised post-mitotic monolayer that maintains retinal homeostasis, contributes to the development of age-related macular degeneration (AMD). Curcumin (Cur), a naturally occurring antioxidant, was previously shown to have the ability to protect RPE cells from oxidative stress. However, poor solubility and bioavailability makes Cur a poor therapeutic agent. As prodrug approaches can mitigate these limitations, we compared the protective properties of the Cur prodrug curcumin diethyl disuccinate (CurDD) against Cur in relation to oxidative stress induced in human ARPE-19 cells. Both CurDD and Cur significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Both drugs exerted their protective effects through the modulation of p44/42 (ERK) and the involvement of downstream molecules Bax and Bcl-2. Additionally, the expression of antioxidant enzymes HO-1 and NQO1 was also enhanced in cells treated with CurDD and Cur. In all cases, CurDD was more effective than its parent drug against oxidative stress-induced damage to ARPE-19 cells. These findings highlight CurDD as a more potent drug compared to Cur against oxidative stress and indicate that its protective effects are exerted through modulation of key apoptotic and antioxidant molecular pathways.

scholarly journals A Solid Dispersion of Quercetin Shows Enhanced Nrf2 Activation and Protective Effects against Oxidative Injury in a Mouse Model of Dry Age-Related Macular Degeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Shao ◽  
Haitao Yu ◽  
Yan Yang ◽  
Min Li ◽  
Li Hang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Solid Dispersion ◽  
Retinal Pigment ◽  
Oxidative Injury ◽  
Age Related Macular Degeneration ◽  
Membrane Thickness ◽  
Protective Effects ◽  
Age Related

Age-related macular degeneration (AMD) represents a major reason for blindness in the elderly population. Oxidative stress is a predominant factor in the pathology of AMD. We previously evaluated the effects of phospholipid complex of quercetin (Q-PC) on oxidative injury in ARPE-19 cells, but the underlying mechanisms are not fully understood. Herein, the solid dispersion of quercetin-PC (Q-SD) was prepared with solubility being 235.54 μg/mL in water and 2.3×104 μg/mL in chloroform, which were significantly higher than that of quercetin (QT) and Q-PC. Q-SD also exhibited a considerably higher dissolution rate than QT and Q-PC. Additionally, Q-SD had Cmax of 4.143 μg/mL and AUC of 12.015 μg·h/mL in rats, suggesting better bioavailability than QT and Q-PC. Then, a mouse model of dry AMD (Nrf2 wild-type (WT) and Nrf2 knockout (KO)) was established for evaluating the effects of Q-SD in vivo. Q-SD more potently reduced retinal pigment epithelium sediments and Bruch’s membrane thickness than QT and Q-PC at 200 mg/kg in Nrf2 WT mice and did not work in Nrf2 KO mice at the same dosage. Additionally, Q-SD significantly decreased ROS and MDA contents and restored SOD, GSH-PX, and CAT activities of serum and retinal tissues in Nrf2 WT mice, but not in Nrf2 KO mice. Furthermore, Q-SD more potently increased Nrf2 mRNA expression and stimulated its nuclear translocation in retinal tissues of Nrf2 WT mice. Q-SD significantly increased the expression of Nrf2 target genes HO-1, HQO-1, and GCL of retinal tissues in Nrf2 WT mice, not in Nrf2 KO mice. Altogether, Q-SD had improved physicochemical and pharmacokinetic properties compared to QT and Q-PC and exhibited more potent protective effects on retina oxidative injury in vivo. These effects were associated with activation of Nrf2 signaling and upregulation of antioxidant enzymes.

Causal Effects of N-6 Polyunsaturated Fatty Acids on Age-related Macular Degeneration: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Kai Wang ◽  
Yueyang Zhong ◽  
Fangkun Yang ◽  
Chenyang Hu ◽  
Xin Liu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Sensitivity Analysis ◽  
Polyunsaturated Fatty Acids ◽  
Macular Degeneration ◽  
Protective Factor ◽  
Mendelian Randomization ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Age Related ◽  
Weighted Median

Abstract Purpose Although the role of n-6 polyunsaturated fatty acids (PUFAs) in age-related macular degeneration (AMD) has been studied in previous observational studies, the precise manner in which one or more n-6 PUFAs account for this relationship remains unclear. Using genetic instruments for n-6 PUFAs traits implemented through mendelian randomization (MR), we aimed to study possible causal associations between n-6 PUFAs and AMD. Methods The two-sample MR method was used to obtain unconfounded causal estimates. We selected genetic variants strongly associated (P < 5×10 -8) with circulating linoleic acid (LA) and arachidonic acid (AA) from a study involving 8,631 individuals and applied to an AMD case-control study (33,526 participants and 16,144 cases). The weighted median and MR Egger methods were used for the sensitivity analysis. Results Our MR analysis suggested that circulating LA was a causal protective factor for AMD, with an odds ratio (OR) estimate of 0.967 (95% confidence interval [CI] 0.945 to 0.990; P = 0.005) per percentage in total fatty acid increase in LA. In contrast, higher genetically predicted circulating AA causally increased the AMD risk (OR = 1.034; 95% CI 1.012 to 1.056; P = 0.002). Sensitivity analysis provided no indication of unknown pleiotropy. The findings from different single-nucleotide polymorphism selections and analytic methods were consistent, suggesting the robustness of the causal associations. Main conclusions Our study provided genetic evidence that circulating LA accounted for protective effects of n-6 PUFAs against the risk of AMD, whereas AA was responsible for deleterious effects on higher AMD risk.

Age related macular degeneration (ARMD) – pathophysiological and clinical features and therapeutic concepts

2001 ◽  
Vol 58 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Ursula Körner-Stiefbold
Keyword(s):  
Macular Degeneration ◽  
Clinical Features ◽  
Altersbedingte Makuladegeneration ◽  
Age Related Macular Degeneration ◽  
Genetische Faktoren ◽  
Age Related ◽  
Therapeutic Concepts

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.

Nutrition in Age-Related Macular Degeneration Survey

2018 ◽  
Author(s):  
Rebekah Stevens ◽  
Richard Cooke ◽  
Hannah Bartlett
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Age Related
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