Review
Biochemistry & Molecular Biology
Jongmin Kim, Yeo Jin Lee, Jae Yon Won
Summary: This review highlights the roles and pathogenesis of retinal pigment epithelium (RPE) in AMD, emphasizing the importance of understanding the etiology of AMD and discussing potential treatment strategies targeting RPE.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Masahiro Miura, Shuichi Makita, Yoshiaki Yasuno, Takuya Iwasaki, Shinnosuke Azuma, Toshihiro Mino, Tatsuo Yamaguchi
Summary: The study quantitatively evaluated retinal pigment epithelium changes in patients with age-related macular degeneration using prototype multi-contrast optical coherence tomography. The results showed that multi-contrast OCT is useful for objective evaluation of changes in the retinal pigment epithelium.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Cody R. Fisher, Mara C. Ebeling, Zhaohui Geng, Rebecca J. Kapphahn, Heidi Roehrich, Sandra R. Montezuma, James R. Dutton, Deborah A. Ferrington
Summary: This study evaluated the treatment response of haRPE and iPSC-RPE to oxidative stress and potential therapeutics for mitochondrial defects. The results showed disease-specific responses in haRPE, while iPSC-RPE had similar responses regardless of disease status. Analysis of cells generated from the same donor showed a similar response for donors without AMD, but significant differences in treatment response between cell models from AMD donors.
Article
Biochemistry & Molecular Biology
Gopalan Gnanaguru, Ashley Mackey, Eun Young Choi, Anthoula Arta, Franco Aparecido Rossato, Thomas W. Gero, Andrew J. Urquhart, David A. Scott, Patricia A. D'Amore, Yin Shan E. Ng
Summary: The research indicates that hindered phenol compounds with protective activities show potential pharmacological value in preserving vision in patients with GA by protecting RPE cells from the toxic effects of oxidized LDL.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Chemistry, Physical
Zhimin Tang, Minfeng Huo, Yahan Ju, Xiaochan Dai, Ni Ni, Yan Liu, Huiqin Gao, Dandan Zhang, Hao Sun, Xianqun Fan, Yu Chen, Ping Gu
Summary: The iron-binding nanoscale Prussian blue analogue CaPB effectively prevents RPE degeneration and subsequent photoreceptor cell degeneration, showing superior therapeutic outcomes in mice upon a single intravitreal injection. The findings suggest that CaPB nanoparticles protect against RPE degradation by inhibiting ferroptotic cell fate, making them promising for future clinical treatment of retinal diseases involving iron-dependent ferroptosis.
Article
Cell Biology
Ha Young Jang, Chang Sik Cho, Young Mi Shin, Jina Kwak, Young Hoon Sung, Byeong-Cheol Kang, Jeong Hun Kim
Summary: This study investigated the mechanisms underlying retinal pigment epithelium dysfunction in aging and age-related macular degeneration (AMD) using primary marmoset cells. Comparisons were made between the effects of fetal bovine serum (FBS) and serum-free supplements on cell characteristics, and age-related morphological changes were assessed. The results suggest that primary marmoset RPE cells provide a reliable in vitro model for developing therapeutics for AMD.
Article
Biochemistry & Molecular Biology
Satoru Ando, Noriyasu Hashida, Daisuke Yamashita, Tsuyoshi Kawabata, Kazunobu Asao, Satoshi Kawasaki, Kazushi Sakurai, Tamotsu Yoshimori, Kohji Nishida
Summary: The study reveals that toxic fluorophore A2E impairs autophagy and upregulates Rubicon in RPE. Treatment with Rubicon-specific siRNA can reverse this impairment, and RPE-specific Rubicon deletion plays a positive role in alleviating retinal inflammation reactions.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sofia Ranta-aho, Niina Piippo, Eveliina Korhonen, Kai Kaarniranta, Maria Hytti, Anu Kauppinen
Summary: The study found that TAS-116 could prevent the activation of caspase-1, subsequently reducing the release of mature IL-1 beta. TAS-116 has a better in vitro therapeutic index than geldanamycin. In summary, TAS-116 appears to be a well-tolerated Hsp90 inhibitor, with the capability to prevent the activation of the NLRP3 inflammasome in human RPE cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Neurosciences
Roberto Pinelli, Michela Ferrucci, Francesca Biagioni, Violet Bumah, Elena Scaffidi, Stefano Puglisi-Allegra, Francesco Fornai
Summary: Defective autophagy in the RPE is involved in AMD, and curcumin can protect RPE cells from damage induced by the autophagy inhibitor 3-MA by activating autophagy.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Hyunchae Sim, Wonhwa Lee, Samyeol Choo, Eui Kyun Park, Moon-Chang Baek, In-Kyu Lee, Dong Ho Park, Jong-Sup Bae
Summary: A study evaluated the protective effects of SFN from cruciferous vegetables against PM2.5-induced oxidative damage, showing that SFN effectively alleviates oxidative damage in human ARPE-19 cells via its antioxidant effects.
FRONTIERS IN MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Santosh Gupta, Lyubomyr Lytvynchuk, Taras Ardan, Hana Studenovska, Georgina Faura, Lars Eide, Ljubo Znaor, Slaven Erceg, Knut Stieger, Jan Motlik, Kapil Bharti, Goran Petrovski
Summary: The retinal pigment epithelium (RPE) plays a crucial role in maintaining the normal physiology of the eye, and damage to the RPE can lead to degenerative eye diseases. Currently, stem cell-derived RPE transplantation is being explored for treating early stages of age-related macular degeneration (AMD). This article focuses on developmental studies and stem cell-based research to understand the biology and derive functional RPEs.
Article
Cell Biology
Mara C. Ebeling, Cody R. Fisher, Rebecca J. Kapphahn, Madilyn R. Stahl, Shichen Shen, Jun Qu, Sandra R. Montezuma, Deborah A. Ferrington
Summary: This study found that the inflammasome is present and active in RPE, but it may not contribute to the pathology of early AMD.
Article
Cell Biology
Wenchang Xu, Xinqi Liu, Wenjuan Han, Keling Wu, Minglei Zhao, Tingfang Mei, Bizhi Shang, Jinwen Wu, Jingyi Luo, Yuhua Lai, Boyu Yang, Yehong Zhuo, Lin Lu, Yizhi Liu, Xiao-li Tian, Ling Zhao
Summary: The overexpression of HTRA1 promotes cellular senescence in RPE, damaging mitochondrial function and activating HIF-1 signaling, which contributes to the pathogenesis of AMD. Inhibition of HIF-1 signaling may serve as a potential therapeutic strategy for AMD.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Multidisciplinary Sciences
Brandi L. Williams, Nathan A. Seager, Jamie D. Gardiner, Chris M. Pappas, Monica C. Cronin, Cristina Amat di San Filippo, Robert A. Anstadt, Jin Liu, Marc A. Toso, Lisa Nichols, Timothy J. Parnell, Jacqueline R. Eve, Paul L. Bartel, Moussa A. Zouache, Burt T. Richards, Gregory S. Hageman
Summary: Research has shown that the HTRA1 gene in the 10q26 locus is downregulated in patients with age-related macular degeneration (AMD) and this is mediated by a noncoding, cis-regulatory element overlapping the ARMS2 intron, potentially leading to an increased risk of disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Pei-Li Yao, Vipul M. Parmar, Mayur Choudhary, Goldis Malek
Summary: The expression and activity of NURR1 play critical roles in the physiological and pathological functions of human RPE cells. Targeting NURR1 may have therapeutic potential for AMD by improving EMT, inflammation, and lipid homeostasis in RPE cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Janusz Blasiak, Ali Koskela, Elzbieta Pawlowska, Mikko Liukkonen, Johanna Ruuth, Elisa Toropainen, Juha M. T. Hyttinen, Johanna Viiri, John E. Eriksson, Heping Xu, Mei Chen, Szabolcs Felszeghy, Kai Kaarniranta
Summary: The common loss of PGC-1 alpha and NFE2L2 genes in aged animals leads to hijacked epithelial-mesenchymal transition, altered RPE morphology, and increased immunoreactivity of senescence markers. These findings suggest that EMT and senescence pathways may intersect in the retinas of dKO mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Juha M. T. Hyttinen, Janusz Blasiak, Szabolcs Felszeghy, Kai Kaarniranta
Summary: Age-related macular degeneration (AMD) is a progressive disease affecting the vision of elderly individuals. The weakening of autophagy clearance has been suggested as an important mechanism in the pathogenesis of AMD, with autophagy-targeting miRNAs potentially playing a crucial role in AMD therapy.
AGEING RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Sofia Ranta-aho, Niina Piippo, Eveliina Korhonen, Kai Kaarniranta, Maria Hytti, Anu Kauppinen
Summary: The study found that TAS-116 could prevent the activation of caspase-1, subsequently reducing the release of mature IL-1 beta. TAS-116 has a better in vitro therapeutic index than geldanamycin. In summary, TAS-116 appears to be a well-tolerated Hsp90 inhibitor, with the capability to prevent the activation of the NLRP3 inflammasome in human RPE cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Janusz Blasiak, Juha M. T. Hyttinen, Joanna Szczepanska, Elzbieta Pawlowska, Kai Kaarniranta
Summary: AMD is the leading cause of visual impairment in the aging population, with age and family history as the strongest risk factors. Long non-coding RNAs play a significant role in the pathogenesis of AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Iswariyaraja Sridevi Gurubaran, Hanna Helotera, Stephen Marry, Ali Koskela, Juha M. T. Hyttinen, Jussi J. Paterno, Arto Urtti, Mei Chen, Heping Xu, Anu Kauppinen, Kai Kaarniranta
Summary: The text discusses the current research status, pathological mechanisms, and animal models of age-related macular degeneration (AMD), focusing on the changes of inflammatory markers in a novel AMD model and their potential significance.
Article
Cell Biology
Toni Tamminen, Ali Koskela, Elisa Toropainen, Iswariyaraja Sridevi Gurubaran, Mateusz Winiarczyk, Mikko Liukkonen, Jussi J. Paterno, Petri Lackman, Amir Sadeghi, Johanna Viiri, Juha M. T. Hyttinen, Ari Koskelainen, Kai Kaarniranta
Summary: The study demonstrates the positive effects of natural pinosylvin extract on age-related macular degeneration, preserving significant retinal function and morphology while reducing chronic oxidative stress. Pinosylvin supplementation may lower the risk of AMD onset and slow down its progression.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Cell Biology
Mooud Amirkavei, Flavia Plastino, Anders Kvanta, Kai Kaarniranta, Helder Andre, Ari Koskelainen
Summary: Cells have stress-response pathways to cope with stress factors for homeostasis maintenance; low doses of stress may be beneficial; HHS was found to enhance autophagy gene expression and activation through HSF1.
Article
Biochemistry & Molecular Biology
Ali Koskela, Federico Manai, Filippo Basagni, Mikko Liukkonen, Michela Rosini, Stefano Govoni, Massimo Dal Monte, Adrian Smedowski, Kai Kaarniranta, Marialaura Amadio
Summary: Antioxidant systems play key roles in elderly diseases, including age-related macular degeneration (AMD). This study investigated the protective effects of nature-inspired hybrids on retinal pigment epithelial (RPE) cells. The hybrids increased the expression of Nrf2-target genes and improved intracellular redox balance without affecting autophagy flux. Furthermore, the hybrids enhanced cell survival and reduced inflammation when exposed to proteasome and autophagy inhibitors. The study suggests that Nrf2 is a valuable target for treating AMD.
Review
Nutrition & Dietetics
Susanne Csader, Sonja Korhonen, Kai Kaarniranta, Ursula Schwab
Summary: The purpose of this study was to evaluate the effect of dietary supplementation on the progression of age-related macular degeneration (AMD). The systematic review and meta-analysis showed that the combination of lutein, zeaxanthin, and n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) supplementation may be beneficial in preventing AMD progression and deterioration of visual function. These results encourage further research on the combination of lutein, zeaxanthin, and n-3 LC-PUFA in early AMD patients.
Review
Cell Biology
Hanna Helotera, Kai Kaarniranta
Summary: Age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population. It is classified into dry and neovascular forms, with neovascular AMD being associated with angiogenesis and inflammatory regulators.
Review
Biochemistry & Molecular Biology
Juha M. T. Hyttinen, Janusz Blasiak, Kai Kaarniranta
Summary: Age-related macular degeneration (AMD) is a complex disease characterized by damage to the retina and is a major cause of vision loss in elderly people. This review explores the role of non-coding RNAs in regulating mitochondrial function and antioxidant stress response in AMD. These molecules have the potential to be used as diagnostic markers and therapeutic targets for AMD and other oxidative stress-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Maeve Boyce, Ying Xin, Olivia Chowdhury, Peng Shang, Haitao Liu, Victoria Koontz, Anastasia Strizhakova, Mihir Nemani, Stacey Hose, J. Samuel Zigler, Matthew Campbell, Debasish Sinha, James T. Handa, Kai Kaarniranta, Jiang Qian, Sayan Ghosh
Summary: This study reveals the interaction between microglia and neutrophils in the pathogenesis of AMD, demonstrating that microglia trigger early RPE changes by regulating neutrophil function and inducing their activation. The study also identifies the Akt2 pathway in microglia as a potential therapeutic target for early AMD.
Article
Biochemistry & Molecular Biology
Maija Toppila, Maria Hytti, Eveliina Korhonen, Sofia Ranta-aho, Niina Harju, Markus M. Forsberg, Kai Kaarniranta, Aaro Jalkanen, Anu Kauppinen
Summary: Increased oxidative stress, dysfunctional cellular clearance, and chronic inflammation are associated with age-related macular degeneration (AMD). Inhibition of PROLY-OLIGOPEPTIDASE (PREP) by KYP-2047 has been shown to reduce oxidative stress and inflammation, and clear cellular protein aggregates.
Article
Pharmacology & Pharmacy
Juha Hyttinen, Janusz Blasiak, Pasi Tavi, Kai Kaarniranta
Summary: AMD is a leading cause of sight loss in the elderly, with most patients lacking treatment options. Targeting PGC-1 alpha may offer a potential therapy, through drug interventions and epigenetic approaches to enhance its expression. This approach could potentially be applied to other disorders associated with disturbances in the mitochondria-antioxidant response-autophagy axis.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
