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
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
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
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
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
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
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
Geriatrics & Gerontology
Nan Su, Uwe Hansen, Tanja Plagemann, Karin Gaeher, M. Dominik Leclaire, Jeannette Konig, Annika Hoehn, Tilman Grune, Constantin E. Uhlig, Nicole Eter, Peter Heiduschka
Summary: LF injection into the subretinal space of mice leads to activation and migration of microglial cells, increased expression of inflammatory cytokines, and gradual degradation of RPE cells. These features are consistent with those found in an aging retina, suggesting that LF injection could serve as a model for intermediate and late AMD.
Article
Ophthalmology
M. Helena Cardoso, Michael J. Hall, Thomas Burgoyne, Pedro Fale, Tina Storm, Cristina Escrevente, Pedro Antas, Miguel C. Seabra, Clare E. Futter
Summary: This study aimed to model the effects of chloroquine on the retinal pigment epithelium in vivo and investigate the impact of mild chloroquine treatment on lysosome function and turnover. The research found that low-dose chloroquine treatment inhibits lysosome reformation, leading to a gradual depletion of lysosomes' ability to interact with cargo-carrying vacuoles and degrade their content. The accumulation of pro-cathepsin D and LAMP1 reflects the inhibition of normal turnover of lysosomal constituents and possibly lysosomes themselves. Understanding the mechanisms underlying lysosome reformation may contribute to the development of new treatments for chloroquine-induced retinopathy.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Chemistry, Medicinal
Shiu-Jau Chen, Tzer-Bin Lin, Hsien-Yu Peng, Hsiang-Jui Liu, An-Sheng Lee, Cheng-Hsien Lin, Kuang-Wen Tseng
Summary: The study demonstrates that fucoxanthin protects RPE cells from oxidative stress-induced premature senescence and decreased photoreceptor cell loss. Fucoxanthin treatment significantly inhibited reactive oxygen species generation and reduced malondialdehyde concentrations in oxidative stress-induced RPE cell damage. Additionally, fucoxanthin may protect against premature senescence and cellular dysfunction in retinal cells exposed to oxidative stress.
Review
Biochemistry & Molecular Biology
Alexa Klettner, Johann Roider
Summary: TLR activation in the retinal pigment epithelium (RPE) can induce a pro-inflammatory response, leading to inflammation by triggering the release of pro-inflammatory cytokines, impairing RPE function, and causing RPE cell degeneration. This constant cycle of TLR activation may contribute to the development of AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Shichen Shen, Rebecca J. Kapphahn, Ming Zhang, Shuo Qian, Sandra R. Montezuma, Peng Shang, Deborah A. Ferrington, Jun Qu
Summary: Age-related macular degeneration (AMD) is a leading cause of blindness in elderly individuals, but treatment options are limited. This study investigates the dysregulation of the proteome in early AMD using human donor retinal pigment epithelium (RPE). Proteomic analysis revealed significant dysregulation in biological functions and pathways, particularly in mitochondrial functions related to translation, ATP metabolism, lipid homeostasis, and oxidative stress. These findings provide valuable insights into the molecular mechanisms of early AMD and can aid in the development of treatments and biomarkers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lara Macchioni, Davide Chiasserini, Letizia Mezzasoma, Magdalena Davidescu, Pier Luigi Orvietani, Katia Fettucciari, Leonardo Salviati, Barbara Cellini, Ilaria Bellezza
Summary: Age-related retinal degenerations, such as AMD, are linked to the loss of RPE cells and photoreceptors, involving oxidative stress and inflammatory responses. Long-term oxidative insult can induce senescence in RPE cells, affecting antioxidant response and mitochondrial functionality.
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
Biochemistry & Molecular Biology
Maria Hytti, Eveliina Korhonen, Heidi Hongisto, Kai Kaarniranta, Heli Skottman, Anu Kauppinen
Summary: The study showed that iPSC-RPE cells from AMD patients exhibit increased secretion of IL-1β and reduced levels of IL-6 and MCP-1 when protein clearance was partially inhibited. This suggests that dysfunctional cellular clearance mechanisms may already be present in cells originating from AMD patients, leading to inflammasome activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Tomokazu Fukuda, Kai Furuya, Kouhei Takahashi, Ai Orimoto, Eriko Sugano, Hiroshi Tomita, Sayo Kashiwagi, Tohru Kiyono, Tsuyoshi Ishii
Summary: This study compared the biological characteristics and genome-wide expression profiles of immortalized human dermal papilla cells generated by different methods to determine the optimal immortalization method. The data would be valuable to scientists aiming to establish new immortalized cell lines.
Article
Biochemistry & Molecular Biology
Yusaku Chukai, Takeshi Iwamoto, Ken Itoh, Hiroshi Tomita, Taku Ozaki
Summary: The study revealed that mitochondrial calpain-5 is activated under low Ca2+ concentrations and in response to endoplasmic reticulum stress, indicating its therapeutic potential in diseases associated with ER stress.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Kai Furuya, Tao Wu, Ai Orimoto, Eriko Sugano, Hiroshi Tomita, Tohru Kiyono, Takahiro Kurose, Yoshihiro Takai, Tomokazu Fukuda
Summary: The study investigated the expression patterns of immortalized corneal epithelial cells with different genetic modifications, showing that SV40 immortalized cells had a distinct expression pattern from wild-type cells regardless of serum presence, while corneal epithelial cells with combinatorial expression had a pattern closer to that of wild-type cells.
Article
Biotechnology & Applied Microbiology
Izzah Munirah, Taku Ozaki, Aya Sekine, Motoko Morimoto, Mayu Sugawara, Haruka Takada, Eriko Sugano, Hiroshi Tomita, Tohru Kiyono, Tomokazu Fukuda
Summary: Dogs are considered as the first animals to establish close relationship with humans, exhibiting unique genetic evolution and diversity. Domestic dogs are used in safety tests of pharmacological products, emphasizing the importance of considering the welfare of experimental animals. In this study, immortalized domestic dog-derived fibroblasts were successfully established as a potential in vivo model system for evaluating pharmacological chemicals without the need for animal testing.
Article
Cell & Tissue Engineering
Yoshito Watanabe, Eriko Sugano, Kitako Tabata, Akito Hatakeyama, Tetsuya Sakajiri, Tomokazu Fukuda, Taku Ozaki, Tomoya Suzuki, Tatsuki Sayama, Hiroshi Tomita
Summary: The research team has successfully increased the light sensitivity of optogenetic gene-mediated therapy by designing mutants, which were used to restore visual responses in rats with genetically degenerating photoreceptor cells. The results suggest that ex3mV1Co may be an effective method for restoring advanced visual function.
NPJ REGENERATIVE MEDICINE
(2021)
Article
Cell Biology
Takenori Oikawa, Tomokazu Fukuda, Tetsuro Yamashita, Hiroshi Tomita, Taku Ozaki
Summary: The study shows that Tat-mu CL has a protective effect, effectively inhibiting glutamate-induced cell death and preventing nuclear translocation of AIF and DNA fragmentation. Therefore, Tat-mu CL may be a potential gene therapy modality for neurodegenerative diseases.
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
(2022)
Review
Neurosciences
Genea Edwards, Caroline G. Olson, Carlyn P. Euritt, Peter Koulen
Summary: The eye is sensitive to oxidative stress, and vitamin E plays a crucial role in protecting against degenerative diseases. Vitamin E has diverse antioxidant activity and can promote neuroprotective effects through several signaling pathways. Further research is needed to fully understand its clinical implications.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yuki Kikuchi, Eriko Sugano, Shiori Yuki, Kitako Tabata, Yuka Endo, Yuya Takita, Reina Onoguchi, Taku Ozaki, Tomokazu Fukuda, Yoshihiro Takai, Takahiro Kurose, Koichi Tanaka, Yoichi Honma, Eduardo Perez, Maxwell Stock, Jose R. Fernandez, Masanori Tamura, Michael Voronkov, Jeffry B. Stock, Hiroshi Tomita
Summary: SIG-1451 partially protects against light-induced photoreceptor degeneration by inhibiting inflammatory responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Daiki Sakai, Hiroshi Tomita, Akiko Maeda
Summary: Optogenetics is a breakthrough in neuroscience with potential applications in treating retinal degenerative diseases. Clinical trials are currently underway to restore vision using optogenetic therapy. Choosing the right optogenetic tools and gene delivery methods is crucial for post-treatment vision improvement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Himari Matsusaka, Tao Wu, Kai Furuya, Tomoe Yamada-Kato, Lanlan Bai, Hiroshi Tomita, Eriko Sugano, Taku Ozaki, Tohru Kiyono, Isao Okunishi, Tomokazu Fukuda
Summary: This study identified downstream target genes involved in testosterone signalling in DPCs through RNA-Seq analysis, providing important data for the discovery of molecular targets for prostate cancer and AGA.
Article
Biochemistry & Molecular Biology
Akito Hatakeyama, Eriko Sugano, Tatsuki Sayama, Yoshito Watanabe, Tomoya Suzuki, Kitako Tabata, Yuka Endo, Tetsuya Sakajiri, Tomokazu Fukuda, Taku Ozaki, Hiroshi Tomita
Summary: Channelrhodopsins have been used in gene therapy to restore vision in patients with retinitis pigmentosa. The channel kinetics of ComV1 variants with different amino acid residues at the 172nd position were investigated. The study found that the characteristics of the amino acid at this position affect the radius of the ion gate, thereby altering the photocurrent and channel kinetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Thomas P. Johnston, Genea Edwards, Peter Koulen
Summary: This study aimed to quantify retina function in a spontaneous mutation mouse model of diabetes, and investigate the effects of hyperglycemia and dyslipidemia on retinal and visual dysfunctions in diabetes. The results showed that the combined presence of hyperglycemia and dyslipidemia had a more severe impact on retinal function.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Yuya Takita, Eriko Sugano, Kazuya Kitabayashi, Kitako Tabata, Akito Saito, Takanori Yokoyama, Reina Onoguchi, Tomokazu Fukuda, Taku Ozaki, Lanlan Bai, Hiroshi Tomita
Summary: This study used multifocal electroretinography to evaluate focal retinal function in rats exposed to continuous light. The results showed a significant decrease in retinal function after 24 hours of light exposure, with a regional dependency in retinal damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Kai Furuya, So Fujibayashi, Tao Wu, Kouhei Takahashi, Shin Takase, Ai Orimoto, Eriko Sugano, Hiroshi Tomita, Sayo Kashiwagi, Tohru Kiyono, Tsuyoshi Ishii, Tomokazu Fukuda
Summary: Testosterone signaling affects the focal adhesion pathway by regulating AR gene expression, with caveolin-1 as a target of AR regulation. This study provides important data resources for the discovery of new therapeutic targets for testosterone-related diseases.
Article
Biochemistry & Molecular Biology
Tetsuya Sakajiri, Masatoshi Nakatsuji, Yoshiaki Teraoka, Kosuke Furuta, Katsuya Ikuta, Kotoe Shibusa, Eriko Sugano, Hiroshi Tomita, Takashi Inui, Takaki Yamamura
Summary: The study investigates the interaction mechanism between ceruloplasmin and transferrin mediated by zinc. The findings suggest that zinc may play a role in the transfer of iron between ceruloplasmin and transferrin.