Article
Cell Biology
Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick McGrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Soren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler
Summary: The study shows that extracellular vesicles secreted by RPE cells are enriched in proteins associated with AMD pathophysiology, exhibiting distinctive directional secretion modes under homeostatic conditions and differential modulation in response to AMD stressors. This suggests a finely-tuned mechanism regulating the secretion of drusen-associated proteins via EVs.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Article
Cell Biology
Qitao Zhang, Feriel Presswalla, Robin R. Ali, David N. Zacks, Debra A. Thompson, Jason M. L. Miller
Summary: The autophagy inducer FLBZ shows promise as a potential therapeutic approach for dry AMD by increasing RPE autophagy flux, reducing lipid deposits, and promoting the production of energy sources.
Article
Biochemistry & Molecular Biology
Viivi Karema-Jokinen, Ali Koskela, Maria Hytti, Heidi Hongisto, Taina Viheriala, Mikko Liukkonen, Tommi Torsti, Heli Skottman, Anu Kauppinen, Soile Nymark, Kai Kaarniranta
Summary: Degeneration and dysfunction of retinal pigment epithelium (RPE) in patients with age-related macular degeneration (AMD) is closely related to protein aggregates formation, protein homeostasis disturbance, inflammation and changes in intracellular Ca2+ concentration. This study investigated autophagy, inflammasome activation, and L-type voltage-gated Ca2+ channels in RPE derived from advanced AMD patients and a control subject. Dysregulated autophagy and inflammasome activation accompanied by reduced intracellular free Ca2+ levels were observed in AMD-RPE. The study also found diminishment of currents through L-type voltage-gated Ca2+ channels and their significant localization in intracellular compartments in AMD-RPE. These findings suggest an important role of Ca2+ signaling in AMD pathogenesis, opening new avenues for therapeutic approaches.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Jeongmin Ho, Ki-Hong Jang, Tae-Sung Koo, Changmin Park, Young-Hoon Kim, Juhee Lee, Eunhee Kim
Summary: This study explored the efficacy of a novel PARP1-inhibitory compound (PIC) in treating dry age-related macular degeneration (AMD) and found that PIC demonstrated superior inhibition compared to existing PARP1 inhibitors. Through in vitro and in vivo experiments, PIC showed potential as an attractive treatment measure for dry AMD.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Henry Velazquez-Soto, Sergio Groman-Lupa, Marisa Cruz-Aguilar, Alberto L. Salazar, Juan C. Zenteno, Maria C. Jimenez-Martinez
Summary: Age-related macular degeneration (AMD) is a complex retinal disease that results in progressive irreversible degeneration of photoreceptors. Oxidative stress, chronic inflammation, and genetic factors, such as the CFH Y402H polymorphism, contribute to AMD pathogenesis. In this study, it was found that ARPE-19 cells with the CFH Y402H variant were more susceptible to oxidative stress-induced damage and exhibited increased levels of inflammatory mediators and pro-apoptotic factors. However, pretreatment with exogenous CFH protected the cells from damage and cell death, possibly through negative regulation of pro-inflammatory cytokines.
Article
Ophthalmology
Ilkay Kilic Muftuoglu, Tiezhu Lin, Dirk-Uwe Bartsch, William R. Freeman
Summary: Longitudinal assessment of patients with dry AMD who underwent vitrectomy did not show exacerbated disease progression. Visual acuity improvement was observed in the study group despite a slight increase in drusen volume following surgery.
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Blanca Chinchilla, Rosario Fernandez-Godino
Summary: Changes in the Bruch's membrane can lead to age-related macular degeneration, with abnormal ECM leading to epithelial mesenchymal transition in RPE cells. Understanding these processes may lead to the development of new therapies for AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Ophthalmology
Mahima Jhingan, Sumit Randhir Singh, Anindya Samanta, Supriya Arora, Davide Tucci, Sohani Amarasekera, Carlo Cagini, Marco Lupidi, Jay Chhablani
Summary: This study longitudinally evaluated 72 eyes with dry AMD and found that eyes with drusen ooze at baseline were more likely to progress to incomplete retinal pigment epithelium and outer retinal atrophy, suggesting that drusen ooze is a useful sign for predicting these advancements over time.
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Audrey Voisin, Afsaneh Gaillard, Anais Balbous, Nicolas Leveziel
Summary: This study found that retinal pigment epithelial (RPE) cells from patients with age-related macular degeneration (AMD) exhibit altered phagocytic activity. The researchers also identified genes related to the mTOR/PI3K-AKT/MEK-ERK pathway that are involved in phagocytosis. These findings indicate a typical disease phenotype in RPE cells from AMD patients.
Article
Biochemistry & Molecular Biology
Michael H. Guerra, Thangal Yumnamcha, Lalit P. Singh, Ahmed S. Ibrahim
Summary: The disruption of retinal pigment epithelial barrier integrity is involved in several blinding retinal diseases. Mitochondrial dysfunction, particularly OxPhos uncoupling, plays a major role in disrupting the barrier function. Identifying the differential roles of mitochondrial components can aid in developing therapeutic approaches for RPE-related retinal diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Xiaojun Wu, Fuwen Yao, Jing-Ying Xu, Jiao Chen, Ying Lu, Wei Li, Jing Deng, Lisha Mou, Qingling Zhang, Zuihui Pu
Summary: This study investigated the effects of H2O2 on human ARPE-19 cells and the protective effects of fullerenol against H2O2-induced oxidative injury using transcriptome and RNA sequencing. The study found that H2O2 affected hub genes and signaling pathways related to the senescence of RPE cells.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Peng Shang, Nadezda A. Stepicheva, Haitao Liu, Olivia Chowdhury, Jonathan Franks, Ming Sun, Stacey Hose, Sayan Ghosh, Meysam Yazdankhah, Anastasia Strizhakova, Donna Beer Stolz, J. Samuel Zigler, Debasish Sinha
Summary: This study introduces a novel and efficient method for RPE explant culture, allowing for obtaining biologically relevant RPE cells in situ, which is beneficial for pharmacological and mechanistic studies. The method involves culturing RPE explants for downstream analysis, such as transduction with adenoviral constructs and chemical treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Anna Duarri, Eduardo Rodriguez-Bocanegra, Gema Martinez-Navarrete, Marc Biarnes, Miriam Garcia, Lucia Lee Ferraro, Bernd Kuebler, Begona Aran, Elisabeth Izquierdo, Eli Aguilera-Xiol, Ricardo P. Casaroli-Marano, Esteve Trias, Eduardo Fernandez, Angel Raya, Anna Veiga, Jordi Mones
Summary: The study demonstrated the feasibility and safety of subretinal transplantation of hiPSC-RPE cells into healthy margins and degenerative areas in a swine model. The engrafted cells formed mature epithelium in healthy retina and interacted with host photoreceptors, but showed irregular distribution and failure to form epithelial-like layer in degenerative areas.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ye Liu, Di Wu, Qiuli Fu, Shengjie Hao, Yuzhou Gu, Wei Zhao, Shuying Chen, Feiyin Sheng, Yili Xu, Zhiqing Chen, Ke Yao
Summary: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. The underlying molecular mechanisms of how retinal pigment epithelial (RPE) cells respond and progress under oxidative damage are still largely unknown. This study reveals the significance of Glutathione specific gamma-glutamylcyclotransferase 1 (Chac1) as a novel contributor of oxidative-stress-induced ferroptosis in RPE, suggesting its potential role in AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Mohana Devi Subramaniam, Mahalaxmi Iyer, Aswathy P. Nair, Dhivya Venkatesan, Sinnakaruppan Mathavan, Nimmisha Eruppakotte, Soumya Kizhakkillach, Manoj Kumar Chandran, Ayan Roy, Abilash Valsala Gopalakrishnan, Balachandar Vellingiri
Summary: Ocular cells, such as retinal pigment epithelium (RPE), play a crucial role in eye health and the development of ocular diseases. High oxygen consumption by retinal cells leads to oxidative stress and the generation of reactive oxygen species (ROS), which can cause RPE degeneration. Gene therapy and cell transplantation are emerging strategies for treating ocular diseases.