Age-Related Macular Degeneration: Pathophysiology, Management, and Future Perspectives

Flores, Rita; Carneiro, Ângela; Vieira, Miguel Bigotte; Tenreiro, Sandra; Seabra, Miguel C.

doi:10.1159/000517520

Cited by 92 publications

(86 citation statements)

References 91 publications

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“…nAMD, also known as wet AMD, is much more likely to lead to irreversible loss of central vision than the dry form (dry AMD). Although nAMD occurs in 10–20% of all AMD patients, this type, due to the rapidly progressive destructive changes associated with the appearance of abnormal vessels under the macula, accounts for the irreversible loss of central vision in 90% of all individuals affected by this disease [ 4 , 21 ]. The predictions for the prevalence of nAMD in the world’s population are highly unfavorable, indicating a significant increase secondary to the aging population in the coming decades, especially in developed countries [ 1 ].…”

Section: Namd and Dme As Global Health Care Problemsmentioning

confidence: 99%

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review

Liberski

Wichrowska

Kocięcki

2022

IJMS

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Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are common retinal vascular diseases responsible for most blindness in the working-age and older population in developed countries. Currently, anti-VEGF agents that block VEGF family ligands, including ranibizumab, bevacizumab (off-label use), brolucizumab, and aflibercept, are the first-line treatment for nAMD and DME. However, due to the complex pathophysiological background of nAMD and DME, non-response, resistance during anti-VEGF therapy, and relapses of the disease are still observed. Moreover, frequent injections are a psychological and economic burden for patients, leading to inadequate adhesion to therapy and a higher risk of complications. Therefore, therapeutic methods are strongly needed to develop and improve, allowing for more satisfactory disease management and lower treatment burden. Currently, the Ang/Tie-2 pathway is a promising therapeutic target for retinal vascular diseases. Faricimab is the first bispecific monoclonal antibody for intravitreal use that can neutralize VEGF and Ang-2. Due to the prolonged activity, faricimab allows extending the interval between successive injections up to three or four months in nAMD and DME patients, which can be a significant benefit for patients and an alternative to implanted drug delivery systems.

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Section: Namd and Dme As Global Health Care Problemsmentioning

confidence: 99%

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review

Liberski

Wichrowska

Kocięcki

2022

IJMS

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“…It is believed that reactive oxygen species-induced apoptotic cascades may play a critical role in AMD (44). From the same viewpoint, drugs which may improve the antioxidant capacity and do good to the mitochondrial integrity may have beneficial effects in fighting against AMD (45).…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Gamma-mangostin on Hydrogen Peroxideinduced Cytotoxicity in Human Retinal Pigment Epithelial Cells

Chien

Mong

et al. 2022

In Vivo

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Background: The role of epigenetic alterations in the pathogenesis of retinal degenerative diseases, such as macular degeneration is not well established. This study aimed to evaluate whether treatments with gamma-mangostin can rescue the hydrogen peroxide (H 2 O 2 )-induced cytotoxicity in human retinal pigment epithelial (ARPE-19) cells. Materials and Methods: ARPE-19 cells were treated with H 2 O 2 alone or with gamma-mangostin plus H 2 O 2 to investigate changes relating to cell viability, appearance of sub-G1 cells, antioxidant enzymes, and apoptotic-related proteins. Results: The data showed that under H 2 O 2 treatment of 400 μM, there was a significant decrease in cell viability and enhanced apoptosis, together with an increased expression of Bax, Bad, at the protein level. On the contrary, the protein expression levels of could effectively prevent all alterations. Conclusion: Gamma-mangostin may conduct its eye-protective effects against H 2 O 2 -induced oxidative damage via antiapoptotic and antioxidant mechanisms in ARPE-19 cells.

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“…Newly created blood vessels leak fluid within the retina, damaging photoreceptors and leading to fibrosis and atrophy of the macula. The only effective treatment for stalling progression of the disease is for the wet form, which includes the injection of VEGF inhibitors into the vitreous ( Flores et al, 2021 ).…”

Section: Environmental Pollutants That Disrupt Endogenous Aryl Hydroc...mentioning

confidence: 99%

“…These environmental components contain polycyclic aromatic hydrocarbons (PAHs) that can serve as ligands of the aryl hydrocarbon receptor (AHR), such as benzo (a) pyrene [B (a) P], dioxins, and hydroquinone ( Hu et al, 2013 ; Julliard et al, 2014 ; Awji et al, 2015 ). Cigarette smoking is the main modifiable risk factor for many eye diseases including: age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, thyroid eye disease (TED), and proliferative vitreoretinopathy (PVR) ( Eliott et al, 2017 ; Lee et al, 2020 ; Molla et al, 2020 ; Flores et al, 2021 ; Gupta et al, 2021 ). Of course, smoke exposure can initiate and contribute to conditions of chronic inflammation and lead to disease ( Lee et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease

Hammond¹,

Roztocil²,

Gupta³

et al. 2022

Front. Toxicol.

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The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor originally identified as an environmental sensor of xenobiotic chemicals. However, studies have revealed that the AHR regulates crucial aspects of cell growth and metabolism, development and the immune system. The importance of the AHR and AHR signaling in eye development, toxicology and disease is now being uncovered. The AHR is expressed in many ocular tissues including the retina, choroid, cornea and the orbit. A significant role for the AHR in age-related macular degeneration (AMD), autoimmune uveitis, and other ocular diseases has been identified. Ligands for the AHR are structurally diverse organic molecules from exogenous and endogenous sources. Natural AHR ligands include metabolites of tryptophan and byproducts of the microbiome. Xenobiotic AHR ligands include persistent environmental pollutants such as dioxins, benzo (a) pyrene [B (a) P] and polychlorinated biphenyls (PCBs). Pharmaceutical agents including the proton pump inhibitors, esomeprazole and lansoprazole, and the immunosuppressive drug, leflunomide, activate the AHR. In this review, we highlight the role of the AHR in the eye and discuss how AHR signaling is involved in responding to endogenous and environmental stimuli. We also present the emerging concept that the AHR is a promising therapeutic target for eye disease.

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Age-Related Macular Degeneration: Pathophysiology, Management, and Future Perspectives

Cited by 92 publications

References 91 publications

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review

Protective Effects of Gamma-mangostin on Hydrogen Peroxideinduced Cytotoxicity in Human Retinal Pigment Epithelial Cells

More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease

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