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Age-Related Macular Degeneration: From Mechanisms to Therapy

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 8983

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Special Issue Editor

Dr. Kwang Won Jeong

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Guest Editor

College of Pharmacy, Gachon University, Incheon, Korea
Interests: epigenetics; gene expression; age-related macular degeneration; histone methylation; autophagy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Age-related macular degeneration (AMD) is a common retinal disease that leads to irreversible central vision loss in the elderly population. AMD is influenced by several genetic and environmental factors, such as genetic alterations, aging, cigarette smoking, and oxidative stress, ultimately leading to local inflammation and cell death in the retina. AMD is diagnosed as either dry type, which is characterized by the accumulation of lipofuscin and deposition of drusen in the Bruch’s membrane, or wet-AMD with choroidal neovascularization. However, the molecular understanding of RPE dysfunction, the mechanism for extracellular deposit accumulation, and neovascularization remain unclear.

This Special Issue invites original articles and reviews focusing on the broad topic of molecular mechanism, in vitro/in vivo models, and experimental/clinical evidence for novel therapies for AMD.

Dr. Kwang Won Jeong
Guest Editor

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Keywords

dry-AMD
wet-AMD
retinal pigment epithelial cell
drusen
lipofuscin
VEGF
neovascularization
inflammation
phototoxicity

Published Papers (6 papers)

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Research

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11 pages, 639 KiB

Open AccessArticle

Factors Associated with Success of Switching to Faricimab for Neovascular Age-Related Macular Degeneration Refractory to Intravitreal Aflibercept

by Akira Machida, Akio Oishi, Junichiro Ikeda, Junko Kurihara, Ai Yoneda, Eiko Tsuiki, Yuki Hirata, Ryuya Murakami and Takashi Kitaoka

Life 2024, 14(4), 476; https://0-doi-org.brum.beds.ac.uk/10.3390/life14040476 - 04 Apr 2024

Viewed by 423

Abstract

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration: From Mechanisms to Therapy)

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11 pages, 259 KiB

Open AccessArticle

Consequences of Real-World Surveillance of Fellow Eyes in Neovascular Age-Related Macular Degeneration

by Oluchukwu Onwuka, Jackson L. Saddemi, Fatma Sema Akkan Aydoğmuş, Claudia C. Lasalle and David J. Ramsey

Life 2023, 13(2), 385; https://0-doi-org.brum.beds.ac.uk/10.3390/life13020385 - 31 Jan 2023

Cited by 3 | Viewed by 1114 | Correction

Abstract

This study investigated whether the interval of monitoring at-risk, fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) has any bearing on the severity of the disease at the time of diagnosis. The study comprised a retrospective, cross-sectional comparative case series of treatment-naïve eyes in patients who were diagnosed sequentially with nAMD. We compared the visual acuity (VA) and central macular thickness (CMT) of patients who were actively receiving intravitreal injections (IVIs) of anti-vascular endothelial growth factor (anti-VEGF) agents at the time of second eye diagnosis with the VA and CMT of patients who had ceased treatment in their first eye because of reaching end-stages of disease. Intervals of visits and frequency of monitoring the macula of fellow eyes by means of optical coherence tomography (OCT) were abstracted from the medical record. We found that the at-risk fellow eyes of patients who had stopped treatment for nAMD in their first eye prior to fellow eye conversion were monitored significantly less frequently than the fellow eyes of patients who continued to receive treatment at the time of second eye diagnosis. Despite less frequent monitoring, VA and CMT were similar at the time of fellow eye diagnosis for both groups. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration: From Mechanisms to Therapy)

12 pages, 1583 KiB

Open AccessArticle

Photooxidation of A2E by Blue Light Regulates Heme Oxygenase 1 Expression via NF-κB and Lysine Methyltransferase 2A in ARPE-19 Cells

by Chae Young Shin and Kwang Won Jeong

Life 2022, 12(11), 1698; https://0-doi-org.brum.beds.ac.uk/10.3390/life12111698 - 25 Oct 2022

Cited by 4 | Viewed by 1258

Abstract

Background: N-retinylidene-N-retinylethanolamine (A2E) is a component of drusen that accumulates in retinal cells and induces oxidative stress through photooxidation, such as blue light (BL). We found that the heme oxygenase 1 (HMOX1) gene responds sensitively to photooxidation by the BL of A2E in retinal pigment epithelial (RPE) cells, and we sought to identify the transcription factors and coactivators involved in the upregulation of HMOX1 by A2E and BL. Methods: A2E-laden human RPE cells (ARPE-19) were exposed to BL (430 nm). RNA sequencing was performed to identify genes responsive to BL exposure. Chromatin immunoprecipitation and RT-qPCR were performed to determine the regulation of HMOX1 transcription. Clinical transcriptome data were used to evaluate HMOX1 expression in patients with age-related macular degeneration (AMD). Results: In ARPE-19 cells, the expression of HMOX1, one of the NF-κB target genes, was significantly increased by A2E and BL. The binding of RELA and RNA polymerase II to the promoter region of HMOX1 was significantly increased by A2E and BL. Lysine methyltransferase 2A (MLL1) plays an important role in H3K4me3 methylation, NF-κB recruitment, chromatin remodeling at the HMOX1 promoter, and, subsequently, HMOX1 expression. The retinal tissues of patients with late-stage AMD showed significantly increased expression of HMOX1 compared to normal retinal tissues. In addition, the expression levels of MLL1 and HMOX1 in retinal tissues were correlated. Conclusions: Taken together, our results suggest that BL induces HMOX1 expression by activating NF-κB and MLL1 in RPE cells. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration: From Mechanisms to Therapy)

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17 pages, 1398 KiB

Open AccessEditor’s ChoiceArticle

SIRT1: Genetic Variants and Serum Levels in Age-Related Macular Degeneration

by Kriste Kaikaryte, Greta Gedvilaite, Alvita Vilkeviciute, Loresa Kriauciuniene, Ruta Mockute, Dzastina Cebatoriene, Reda Zemaitiene, Vilma Jurate Balciuniene and Rasa Liutkeviciene

Life 2022, 12(5), 753; https://0-doi-org.brum.beds.ac.uk/10.3390/life12050753 - 19 May 2022

Viewed by 1759

Abstract

Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was performed using RT-PCR. SIRT1 serum level was determined using the ELISA method. Results: We found that rs3818292 and rs7895833 were associated with an increased risk of developing exudative AMD. Additional sex-differentiated analysis revealed only rs7895833 was associated with an increased risk of developing exudative AMD in women after strict Bonferroni correction. The analysis also revealed that individuals carrying rs3818292, rs3758391 and rs7895833 haplotype G-T-G are associated with increased odds of exudative AMD. Still, the rare haplotypes were associated with the decreased odds of exudative AMD. After performing an analysis of serum SIRT1 levels and SIRT1 genetic variant, we found that carriers of the SIRT1 rs3818292 minor allele G had higher serum SIRT1 levels than the AA genotype. In addition, individuals carrying at least one SIRT1 rs3758391 T allele also had elevated serum SIRT1 levels compared with individuals with the wild-type CC genotype. Conclusions: Our study showed that the SIRT1 polymorphisms rs3818292 and rs7895833 and rs3818292-rs3758391-rs7895833 haplotype G-T-G could be associated with the development of exudative AMD. Also, two SNPs (rs3818292 and rs3758391) are associated with elevated SIRT1 levels. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration: From Mechanisms to Therapy)

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Review

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26 pages, 1976 KiB

Open AccessReview

Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration

by Himanshu Paliwal, Bhupendra Gopalbhai Prajapati, Teerapol Srichana, Sudarshan Singh and Ravish J. Patel

Life 2023, 13(2), 568; https://0-doi-org.brum.beds.ac.uk/10.3390/life13020568 - 17 Feb 2023

Cited by 3 | Viewed by 3229

Abstract

The number of patients with ocular disorders has increased due to contributing factors such as aging populations, environmental changes, smoking, genetic abnormalities, etc. Age-related macular degeneration (AMD) is one of the common ocular disorders which may advance to loss of vision in severe cases. The advanced form of AMD is classified into two types, dry (non-exudative) and wet (exudative) AMD. Although several therapeutic approaches are explored for the management of AMD, no approved therapy can substantially slow down the progression of dry AMD into the later stages. The focus of researchers in recent times has been engaged in developing targeted therapeutic products to halt the progression and maintain or improve vision in individuals diagnosed with AMD. The delivery of anti-VEGF agents using intravitreal therapy has found some success in managing AMD, and novel formulation approaches have been introduced in various studies to potentiate the efficacy. Some of the novel approaches, such as hydrogel, microspheres, polymeric nanoparticles, liposomes, implants, etc. have been discussed. Apart from this, subretinal, suprachoroidal, and port delivery systems have also been investigated for biologics and gene therapies. The unmet potential of approved therapeutic products has contributed to several patent applications in recent years. This review outlines the current treatment options, outcomes of recent research studies, and patent details around the novel drug delivery approach for the treatment of AMD. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration: From Mechanisms to Therapy)

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