Oxidative stress as a therapeutic target for the prevention and treatment of early age-related macular degeneration

Jabbehdari, Sayena; Handa, James T.

doi:10.1016/j.survophthal.2020.09.002

Cited by 38 publications

(28 citation statements)

References 242 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it is reasonable to take into consideration a combinational therapy targeting complement system and RPE cells at the same time. For instance, several antioxidants agents and potential mitochondrial protective substances have been suggested as cytoprotective options for RPE cells in AMD [159,160].…”

Section: Complement-mediated Therapeutic Strategies For Treating Amdmentioning

confidence: 99%

The complement system in age-related macular degeneration

Armento

Ueffing

Clark

2021

Cell. Mol. Life Sci.

141

128

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.

show abstract

Section: Complement-mediated Therapeutic Strategies For Treating Amdmentioning

confidence: 99%

The complement system in age-related macular degeneration

Armento

Ueffing

Clark

2021

Cell. Mol. Life Sci.

141

128

View full text Add to dashboard Cite

show abstract

“…For this purpose, we used a murine model of NaIO 3 -induced retinal degeneration in vivo and in human RPE and LPS-induced oxidative stress in RAW264.7 macrophages. Oxidative stress has long been recognized as a contributing factor to the pathogenesis of AMD [ 2 , 4 , 5 ]. A commonly used experimental model to study the link between oxidative stress and AMD involves the use of cultured human RPE (ARPE19) cells [ 4 , 8 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…A commonly used experimental model to study the link between oxidative stress and AMD involves the use of cultured human RPE (ARPE19) cells [ 4 , 8 , 11 ]. Thus, it would be of great significance to explore the oxidative damage of RPE cells in order to examine the pathogenesis and treatment of AMD [ 5 , 24 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…SI as a retinotoxin that is directly toxic to RPE by oxidative stress and consequently induces retinal degeneration [ 2 , 4 , 5 ]. To confirm that paprika fermentation is more useful for treating oxidative stress-induced ocular degeneration, we used a SI-induced retinal degeneration model in ARPE-19 cells and mice.…”

Section: Discussionmentioning

confidence: 99%

“…ROS are generated from aerobic metabolism under pathophysiologic conditions that can induce oxidative damage. Imbalanced intracellular ROS can alter essential physiological signaling, such as regulatory feedback related to metabolism, hypoxia, and inflammation, that can impair RPE cell function [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Protective Effects of Fermented Paprika (Capsicum annuum L.) on Sodium Iodate-Induced Retinal Damage

Kim

Lee³

et al. 2020

Nutrients

View full text Add to dashboard Cite

Diseases of the outer retina, including age-related macular degeneration (AMD), are major cause of permanent visual damage. The pathogenesis of AMD involves oxidative stress and damage of the retinal pigment epithelium. Capsicum annuum L. (paprika) fruits have been known as a source of vitamins, carotenoids, phenolic compounds, and metabolites with a well-known antioxidant activity, which have positive effects on human health and protection against AMD and cataracts. In this study, we investigated whether paprika (fermented (FP), yellow, and orange colored) fermented with Lactobacillus (L.) plantarum could increase the protective effect of retinal degeneration using in vitro and in vivo models. FP significantly increased cell survival and reduced levels of lactate dehydrogenase as well as intracellular reactive oxygen species (ROS) increase in SI (sodium iodate, NaIO3)-treated human retinal pigment epithelial (ARPE-19) cells. We developed a model of retinal damage in C57BL/6 mice using SI (30 mg/kg) via intraperitoneal injection. Seven days after SI administration, deformation and a decrease in thickness were observed in the outer nuclear layer, but improved by FP treatment. FP administration protected the SI-mediated reduction of superoxide dismutase and glutathione levels in the serum and ocular tissues of mice. The overproduction of cleaved poly(ADP-Ribose) Polymerase (PARP)1, caspase-3 and -8 proteins were significantly protected by FP in SI-treated cells and ocular tissues. In addition, we evaluated the potentiating effects of FP on antioxidants and their underlying mechanisms in RAW 264.7 cells. Lipopolysaccharide (LPS)-induced nitrite increase was markedly blocked by FP treatment in RAW 264.7 cells. Furthermore, FP reduced LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 activation. The FP also enhanced the inhibitory effects on mitogen activated kinase signaling protein activation in ARPE-19 and RAW 264.7 cells and ocular tissues. There was no significant difference in total phenol and flavonoid content in paprika by fermentation, but the vitamin C content was increased in orange colored paprika, and protective effect against oxidative stress-mediated retinal damage was enhanced after fermentation. These results suggest that FP may be a potential candidate to protect against retinal degenerative diseases through the regulation of oxidative stress.

show abstract

Polydopamine Nanoparticles as Mimicking RPE Melanin for the Protection of Retinal Cells Against Blue Light‐Induced Phototoxicity

Kwon,

Munsoor,

Kaufmann

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Exposure of the eyes to blue light can induce the overproduction of reactive oxygen species (ROS) in the retina and retinal pigment epithelium (RPE) cells, potentially leading to pathological damage of age‐related macular degeneration (AMD). While the melanin in RPE cells absorbs blue light and prevents ROS accumulation, the loss and dysfunction of RPE melanin due to age‐related changes may contribute to photooxidation toxicity. Herein, a novel approach utilizing a polydopamine‐replenishing strategy via a single‐dose intravitreal (IVT) injection is presented to protect retinal cells against blue light‐induced phototoxicity. To investigate the effects of overexposure to blue light on retinal cells, a blue light exposure Nrf2‐deficient mouse model is created, which is susceptible to light‐induced retinal lesions. After blue light irradiation, retina degeneration and an overproduction of ROS are observed. The polydopamine‐replenishing strategy demonstrated effectiveness in maintaining retinal structural integrity and preventing retina degeneration by reducing ROS production in retinal cells and limiting the phototoxicity of blue light exposure. These findings highlight the potential of polydopamine as a simple and effective replenishment for providing photoprotection against high‐energy blue light exposure.

show abstract

Oxidative stress as a therapeutic target for the prevention and treatment of early age-related macular degeneration

Cited by 38 publications

References 242 publications

The complement system in age-related macular degeneration

The complement system in age-related macular degeneration

Protective Effects of Fermented Paprika (Capsicum annuum L.) on Sodium Iodate-Induced Retinal Damage

Polydopamine Nanoparticles as Mimicking RPE Melanin for the Protection of Retinal Cells Against Blue Light‐Induced Phototoxicity

Contact Info

Product

Resources

About