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
Cell & Tissue Engineering
Ioannis J. Limnios, Yu-Qian Chau, Stuart J. Skabo, Denver C. Surrao, Helen C. O'Neill
Summary: This study developed a rapid and efficient method for producing retinal RPE cells from human embryonic stem cells (hESCs) using small molecules. The RPE cells exhibited key morphological, molecular, and functional characteristics of endogenous RPE, showing potential for clinical-grade cell production to treat AMD.
STEM CELL RESEARCH & THERAPY
(2021)
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
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)
Review
Ophthalmology
Amir H. Kashani
Summary: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. Stem cell-based therapies show promising potential for treating advanced stages of the disease. Recent clinical trials have demonstrated safety and preliminary efficacy, but challenges remain in selecting the most appropriate cell-based therapy and managing immune responses.
CURRENT OPINION IN OPHTHALMOLOGY
(2022)
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
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.
Review
Immunology
Yicheng Mo, Jiabing Ma, Hongtao Zhang, Junjie Shen, Jun Chen, Juan Hong, Yanmin Xu, Cheng Qian
Summary: This article discusses the classification, mechanism, and clinical effects of HPV vaccines for the prevention and treatment of cervical cancer and other malignant cancers. While vaccines have been successful in preventing 90% of HPV infections worldwide, they do not have a significant therapeutic effect on existing infections and lesions.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Yunlong Cao, Weiliang Song, Lei Wang, Pan Liu, Can Yue, Fanchong Jian, Yuanling Yu, Ayijiang Yisimayi, Peng Wang, Yao Wang, Qianhui Zhu, Jie Deng, Wangjun Fu, Lingling Yu, Na Zhang, Jing Wang, Tianhe Xiao, Ran An, Lu Liu, Sijie Yang, Xiao Niu, Qingqing Gu, Fei Shao, Xiaohua Hao, Bo Meng, Ravindra Kumar Gupta, Ronghua Jin, Youchun Wang, Xiaoliang Sunney Xie, Xiangxi Wang
Summary: The newly emerged SARS-CoV-2 Omicron subvariant, BA.2.75, has shown a growth advantage over other circulating variants in India. This study reveals that BA.2.75 has a higher affinity for the host receptor ACE2 and exhibits increased low-pH-endosomal cell entry. It also demonstrates reduced evasion of humoral immunity from certain convalescent plasma, while showing a distinct neutralizing antibody escape pattern. These findings suggest that BA.2.75 may become the dominant variant following BA.4/BA.5.
CELL HOST & MICROBE
(2022)
Review
Chemistry, Medicinal
Minghui Li, Lixiong Gao, Ling Zhao, Ting Zou, Haiwei Xu
Summary: Thanks to advancements in 3D culture technologies, organoids derived from human stem cells have provided valuable insights into human CNS development and diseases. However, current organoid cultivation protocols still struggle to recapitulate the complexity and maturation of in vivo neural tissues. Recent studies have explored bioengineering techniques such as genetic engineering, coculture, multidifferentiation, microfluidics, 3D bioprinting, and transplantation to enhance organoid maturation and functionality. These methods hold promise in generating more reliable in vitro models for studying human CNS.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Neurosciences
Zhenle Zang, Huachun Yin, Zhulin Du, Ruxin Xie, Ling Yang, Yun Cai, Liuyongwei Wang, Dandan Zhang, Xin Li, Tianyao Liu, Hong Gong, Junwei Gao, Hui Yang, Margaret Warner, Jan-Ake Gustafsson, Haiwei Xu, Xiaotang Fan
Summary: Exposure to valproic acid during pregnancy increases the risk of autism spectrum disorder in children. In this study, human dorsal forebrain organoids were used to model the effects of VPA exposure on cortical neurogenesis. The findings showed that VPA exposure reduced the size of neural progenitor cells and impaired their proliferation and expansion. It also delayed the development of certain types of cells and influenced the expression of ASD risk genes. The activation of the Wnt/beta-catenin signaling pathway was identified as essential for sustaining cortical neurogenesis.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Materials Science, Multidisciplinary
Jing Liu, Hongli Suo, Zili Zhang, Yaotang Ji, Jiazhi Li, Lanjin Wang, Lei Wang, Qiuliang Wang
Summary: The Ni-5 at.%W/Ni-9.3 at.%W/Ni-5 at.%W alloy composite substrate with a thickness of 109 mu m was produced by powder metallurgy and rolling process. The cubic texture of the composite substrates reached 97.3% even when the thickness was reduced to 72 mu m. However, the saturation magnetization was only 2.3 (emu/g). The formation of cubic-oriented grains was hindered by twin defects in the inner layer.
MATERIALS SCIENCE AND TECHNOLOGY
(2023)
Article
Environmental Sciences
Ling Yang, Jiao Zou, Zhenle Zang, Liuyongwei Wang, Zhulin Du, Dandan Zhang, Yun Cai, Minghui Li, Qiyou Li, Junwei Gao, Haiwei Xu, Xiaotang Fan
Summary: Using a human cerebral organoid model, researchers found that DEHP exposure inhibited cell proliferation and increased apoptosis, impairing the morphogenesis of the human cerebral cortex. DEHP exposure disrupted neurogenesis and neural progenitor migration, possibly due to dysplasia of radial glia cells. RNA sequencing analysis showed that DEHP-induced disorder in cell-extracellular matrix interactions might play a crucial role in the neurodevelopment of human cerebral organoids.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Chemistry, Multidisciplinary
Guiming Hu, Yan Fang, Haiwei Xu, Guanzhe Wang, Rui Yang, Fei Gao, Qingda Wei, Yuhan Gu, Cunzhen Zhang, Jinhuan Qiu, Na Gao, Qiang Wen, Hailing Qiao
Summary: The overexpression of CYP2E1 is closely related to higher malignancy in GBM patients. Increased inflammation is accompanied by significantly higher CYP2E1 expression in a mouse GBM model. The specific inhibitor Q11 can effectively attenuate tumor growth and prolong survival in vivo.
Article
Chemistry, Multidisciplinary
Fanchu Zeng, Zhijin Fan, Shiying Li, Lanqing Li, Tong Sun, Yang Qiu, Liming Nie, Guojia Huang
Summary: This study presents an all-in-one theranostic nanoprobe for precise chemotherapy and real-time immune response tracing of glioblastoma. The nanoprobe effectively targets regulatory T lymphocytes and can be monitored using photoacoustic-fluorescence imaging. The combination of chemotherapy and immunotherapy shows promising results in enhancing immune response and reducing lymphocyte infiltration.
Article
Chemistry, Multidisciplinary
Junling Yang, Xia Chen, A. Luodan, Hui Gao, Maoru Zhao, Lingling Ge, Minghui Li, Cao Yang, Yu Gong, Zhanjun Gu, Haiwei Xu
Summary: The synthesized fullerenols exhibit efficient radical scavenging abilities in vitro. Fullerenol-based intravitreal injections significantly improve the visual function and structural integrity of the retina in rd1 mice. These findings suggest that fullerenols could be a promising therapeutic option for retinitis pigmentosa.
Article
Cell & Tissue Engineering
Houjian Zhang, Yuli Guo, Yaqiong Yang, Yuqian Wang, Youwen Zhang, Jingbin Zhuang, Yuting Zhang, Mei Shen, Jiankai Zhao, Rongrong Zhang, Yan Qiu, Shiying Li, Jiaoyue Hu, Wei Li, Jianfeng Wu, Haiwei Xu, Steven J. Fliesler, Yi Liao, Zuguo Liu
Summary: This study found that three MAP4K proteins restrict the transdifferentiation ability of mammalian Muller glia by repressing YAP activity. However, inhibition of these proteins with a small molecule allows mouse Muller glia to regain their proliferative ability and enter a retinal progenitor cell-like state. This finding provides important insights for stimulating retinal regeneration.
NPJ REGENERATIVE MEDICINE
(2023)
Article
Cell & Tissue Engineering
Yu Gong, Lingling Ge, Qiyou Li, Jing Gong, Min Chen, Hui Gao, Jiahui Kang, Ting Yu, Jiawen Li, Haiwei Xu
Summary: Fetal Alcohol Syndrome (FAS) significantly affects more than 90% of affected children, causing severe ocular aberrations. This study used human embryonic stem cells derived retinal organoids (hROs) to simulate the initial neurogenesis of the human embryonic neural retina and found that 1% ethanol slows down the growth of hROs, leading to cell death and retinal ganglion cell differentiation defect. The study also identified the calcium-binding protein RET as a key player in the ethanol-induced neurogenesis disruption. Overall, this study provides insights into the effects and molecular mechanisms of ethanol exposure on the development of the human neural retina and may inform preventative measures for FAS.
STEM CELL REVIEWS AND REPORTS
(2023)
Article
Biochemical Research Methods
Jing Gong, Yu Gong, Ting Zou, Yuxiao Zeng, Cao Yang, Lingyue Mo, Jiahui Kang, Xiaotang Fan, Haiwei Xu, Jun Yang
Summary: A controllable perfusion microfluidic chip (CPMC) was designed to culture retinal organoids (ROs) derived from human pluripotent stem cells. The results demonstrated that this system allowed for expansion of retinal progenitor cell (RPC) pool, orchestration of retinal ganglion cell (RGC) specification, and axon growth. This study highlights the advantages of the CPMC in promoting RO growth and providing a controllable platform for the maturity of RGCs, with promising applications in modeling RGC-related disorders, drug screening, and cell transplantation.
Article
Cell & Tissue Engineering
Jiahui Kang, Jing Gong, Cao Yang, Xi Lin, Lijuan Yan, Yu Gong, Haiwei Xu
Summary: The intricate neural circuit of the retina forms bioelectric impulses as the origin of vision, and the early development of the retina is a highly complex and coordinated process. Evidence shows that stem cells derived human retinal organoids (hROs) can faithfully recapitulate the embryonic developmental process of the human retina. The emergence of hROs deepens the understanding of early development of the human retina.
STEM CELL REVIEWS AND REPORTS
(2023)
Article
Medicine, Research & Experimental
Xuan Cheng, Hui Gao, Zui Tao, Zhiyuan Yin, Zhe Cha, Xiaona Huang, Yikui Zhang, Yuxiao Zeng, Juncai He, Lingling Ge, A. Luodan, Haiwei Xu, Guang-Hua Peng
Summary: In zebrafish, microglia play a role in reprogramming Müller glia (MG) into retinal progenitors and repairing injured retina, while in mammals, microglia are over-activated during retinal injury, causing inflammation and gliosis of MG. Modulating the phenotype of microglia to enhance MG reprogramming is critical.
Article
Oncology
Xiuxiu Zhu, Wuling Li, Jiadong Gao, Junjie Shen, Yanmin Xu, Chengcheng Zhang, Cheng Qian
Summary: CAR-T therapy has shown success in treating certain types of hematological malignancies, but its efficacy in treating solid tumors is limited. Improving the exhaustion of CAR-T cells is an inspiring strategy for CAR-T treatment of solid tumors.