Article
Neurosciences
Aaron Krylov, Shuguang Yu, Kellie Veen, Axel Newton, Aojun Ye, Huiwen Qin, Jie He, Patricia R. Jusuf
Summary: In this study, single-cell RNA sequencing revealed heterogeneity in gene expression within quiescent Muller glia. Additionally, the researchers found a region-specific bias in the activation of Muller glia following selective ablation of different photoreceptor subtypes. These findings provide important insights into the molecular mechanisms of neural regeneration in the retina.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Hsing-Chun Kuo, Shiou-Lan Chen, Shu-Chen Chiu, Kam-Fai Lee, Chun-Hsien Chu
Summary: The development of microglial endotoxin tolerance (ET) plays a critical role in protecting neurons, and this study aimed to investigate the mechanisms involved. The results showed that LPS-induced TNF-a tolerance in microglia depended on LBP. Additionally, early pro-inflammatory cytokines induced by LPS did not contribute to microglial ET. Moreover, inhibition of p38 MAPK disrupted the microglial TNF-a reduction and neuroprotection.
Article
Ophthalmology
Annette Zwanzig, Jie Meng, Heidi Mueller, Susanne Buerger, Manuela Schmidt, Maik Pankonin, Peter Wiedemann, Jan Darius Unterlauft, Wolfram Eichler
Summary: Secreted neuroprotective factors produced by Muller cells can promote RGC survival, and R28 cells are more resistant to apoptosis when co-cultured with Muller cells. Under hypoxia, IL-6 and VEGF are upregulated in Muller cells, and these factors can also alter the expression of Bcl-2 family members, which regulate apoptosis.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jing-Ting Chiou, Yi-Jun Shi, Yuan-Chin Lee, Liang-Jun Wang, Ying-Jung Chen, Long-Sen Chang
Summary: SEM-LA activates TNF-α-mediated apoptosis in U937 cells through the NOX4/p38 MAPK/PP2A axis and promotes this process via Ca2+-NOX4-ROS axis-mediated p38 MAPK activation. Restoration of TTP expression alleviates the effects of TNF-α upregulation and cell death induced by SEM-LA.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Ophthalmology
K. Eastlake, W. D. B. Lamb, J. Luis, P. T. Khaw, H. Jayaram, G. A. Limb
Summary: Neural cell death is the main cause of blindness in retinal degenerative diseases, with recent stem cell research and the identification of Muller glial cells providing hope for potential therapies. However, there is currently no evidence to suggest that they promote regeneration in humans.
PROGRESS IN RETINAL AND EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yun-Zheng Le, Bei Xu, Ana J. Chucair-Elliott, Huiru Zhang, Meili Zhu
Summary: The study demonstrated that VEGF plays a positive regulatory role in promoting BDNF production in diabetes, while BDNF can support MC survival under diabetic conditions. Targeting the BDNF receptor TRK-B can affect the activity of survival and proliferation mediators such as AKT and ERK, and rescuing MC viability loss under diabetic conditions was achieved through rBDNF.
Article
Neurosciences
Warren A. Campbell, Amanda Fritsch-Kelleher, Isabella Palazzo, Thanh Hoang, Seth Blackshaw, Andy J. Fischer
Summary: Studies show that MDK expression in the retina is regulated by Muller glia, leading to effects on neuronal survival and the formation of MGPCs. MDK plays a crucial role in mediating glial activity and promoting the reprogramming of Muller glia into proliferating MGPCs.
Article
Cell Biology
Kaida Song, Zihao Lin, Lining Cao, Bowen Lu, Yuxi Chen, Shuqiang Zhang, Jianfeng Lu, Hui Xu
Summary: The zebrafish Sox11 homolog, Sox11b, regulates the migration and fate determination of Muller glia-derived progenitors (MGPCs) during retina regeneration. Sox11b knockdown alters nuclear morphology and radial migration of MGPCs, leading to changes in their distribution within the retina. Additionally, Sox11b knockdown affects photoreceptor regeneration and the numbers of newborn amacrines and retinal ganglion cells. Notch signaling is found to function downstream of Sox11b in this process. These findings highlight the key roles of Sox11b in MGPC migration and fate determination during retina regeneration in zebrafish and have implications for future retinal repair research in mammals.
NEURAL REGENERATION RESEARCH
(2023)
Review
Cell Biology
Joseph Hanna, Luke Ajay David, Yacine Touahri, Taylor Fleming, Robert A. Screaton, Carol Schuurmans
Summary: This article discusses the connection between photoreceptor degeneration and alterations in cell metabolism, as well as how metabolic reprogramming drives retinal development and repair. Specifically, it explores the potential of reactivating the regenerative properties of Muller glia in mammals. The article also draws insights from other tissues and regenerative species.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Juan S. Pena, Maribel Vazquez
Summary: Progressive and irreversible vision loss in mature and aging adults creates a global burden, and the neuroprotective abilities of retinal glial cells (Muller glia) have not been fully explored and utilized for vision restoration.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2022)
Review
Oncology
Yaosheng Luo, Xiao Wang, Jie Shen, Jie Yao
Summary: Leukemia is a group of malignant diseases involving clonal hematopoietic stem-progenitor cells, with genetic and epigenetic abnormalities, as well as microenvironmental factors, playing critical roles in its development. Macrophage migration inhibitory factor (MIF) is a key regulator in tumorigenesis, angiogenesis, and tumor metastasis, with its upregulation promoting a pro-tumor microenvironment and pro-inflammatory cytokine production in response to hypoxia-induced factors. Early clinical trials targeting the MIF signal have shown promising results for intervention in leukemia.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Songling Hu, Lin Zhu, Yimeng Song, Xinrui Zhao, Qianping Chen, Yan Pan, Jianghong Zhang, Yang Bai, Haowen Zhang, Chunlin Shao
Summary: This study revealed that hypofractionated irradiation on the thorax can cause distant testicular damage and result in radiation-induced abscopal reproductive effects (RIARE) in male mice. Mechanistically, thoracic irradiation induced nuclear translocation of Rac1 and activation of the TNF-alpha/p38 MAPK pathway. The interaction between YWHAZ and Rac1 is critical for the detrimental reproductive effects induced by thoracic irradiation.
Article
Pharmacology & Pharmacy
Baocheng Xie, Zhanwei Zeng, Shiyi Liao, Chenhui Zhou, Longhuo Wu, Daohua Xu
Summary: Kaempferol exhibits beneficial effects on osteogenic differentiation and counteracts the inhibitory activity of dexamethasone by activating JNK and p38-MAPK signaling pathways, improving bone mineralization. This potential makes it a promising candidate for developing new drugs for treating glucocorticoid-induced osteoporosis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yuan-Chin Lee, Jing-Ting Chiou, Long-Sen Chang
Summary: The study aimed to investigate the cytotoxic effects of the AMPK inhibitor Compound C in chronic myeloid leukemia (CML) cell lines. Compound C induced apoptosis in certain CML cell lines, and its effects were enhanced by the silencing of SIRT3. Autophagy and downregulation of MCL1 were observed in response to Compound C treatment. The study suggests that AMPK inhibition is a promising strategy for improving CML therapy.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Oncology
Y. Loriot, A. Marabelle, J. P. Guegan, F. X. Danlos, B. Besse, N. Chaput, C. Massard, D. Planchard, C. Robert, C. Even, M. Khettab, L. Tselikas, L. Friboulet, F. Andre, I Nafia, F. Le Loarer, J. C. Soria, A. Bessede, A. Italiano
Summary: This study analyzed the proteome of cancer patients treated with ICB and found that elevated baseline levels of leukemia inhibitory factor (LIF) were associated with poor clinical outcomes. The study also revealed that the circulating level of LIF was inversely correlated with tertiary lymphoid structures in the tumor microenvironment. Targeting LIF or its pathway may represent a promising approach to improve efficacy of cancer immunotherapy in combination with ICB.
ANNALS OF ONCOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Claudia C. Bippes, Corina Kohler, Esther Garcia-Tirado, Reto Burri, Tina Frauenknecht, Marie-Apolline Gerard, Marie Salat, Roy Allenspach, Cavit Agca, Zongsong Wu, Andrea Trost, Barbara Bogner, Peter Meyer, Hendrik P. N. Scholl, Herbert Reitsamer, Josef Flammer, Albert Neutzner
Summary: Cell-penetrating peptides (CPPs) have great potential for intracellular delivery of therapeutic proteins, but endosomal entrapment hinders their successful application. By utilizing endosome-resident proteases to sever the artificial transcription factor from its CPP, we enhanced the subcellular localization and biological activity of the disentangled artificial transcription factor.
Article
Biology
Duygu Karademir, Vyara Todorova, Lynn J. A. Ebner, Marijana Samardzija, Christian Grimm
Summary: This study utilizes droplet-based single-cell RNA sequencing to investigate the degeneration process in rod and cone photoreceptor cells in an RP mouse model. The results identify early changes in rods and potential early responses in cones, suggesting mechanisms involved in secondary cone degeneration. Furthermore, the study implicates EGR1 as a potential key regulator of early degenerative events in both types of photoreceptor cells.
Article
Biochemistry & Molecular Biology
Florian Peters, Lynn J. A. Ebner, David Atac, Jordi Maggi, Wolfgang Berger, Anneke den Hollander, Christian Grimm
Summary: This study focuses on analyzing the dysregulation of ATP-binding cassette transporter A1 (ABCA1) in induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) cells. The results show that genetic variations associated with age-related macular degeneration (AMD) result in increased ABCA1 gene expression, reduced cholesterol efflux, and increased lipid accumulation. Additionally, hypoxia decreases ABCA1 expression and increases intracellular lipid accumulation. Stimulating ABCA1 expression could improve RPE cell survival and reduce the risk of developing AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Divya Ail, Duohao Ren, Elena Brazhnikova, Celine Nouvel-Jaillard, Stephane Bertin, Seyed Bagher Mirashrafi, Sylvain Fisson, Deniz Dalkara
Summary: This study investigates the potential inflammatory responses in AAV-mediated retinal gene therapy and the correlation between pre-existing serum antibodies and clinical outcomes. The results show a dose-dependent increase in antibodies after injection, and a correlation between serum antibody levels, inflammation, and transgene expression.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Annie L. Miller, Paula Fuller-Carter, Klaudija Masarini, Marijana Samardzija, Kim W. Carter, Rabab Rashwan, Xin Ru Lim, Alicia A. Brunet, Abha Chopra, Ramesh Ram, Christian Grimm, Marius Ueffing, Livia S. Carvalho, Dragana Trifunovic
Summary: Inherited retinal diseases (IRDs) are a group of blinding disorders that affect the cone and rod photoreceptors. This study explores the potential therapeutic benefits of a histone demethylase inhibitor, GSK-J4, on cone cell survival in a mouse model of achromatopsia. The results suggest that epigenetic modulation of histones may be a promising approach in slowing down cone degeneration in IRDs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Neurosciences
Divya Ail, Marijana Samardzija, Andy C. M. Chang, Jadwiga Keck, Roger R. Reddel, Christian Grimm
Summary: This study investigated the expression of stanniocalcins in the retina and found that Stc2 was induced in acute and chronic hypoxia models, regulated by HIF1, while Stc1 remained stable. Furthermore, Stc2 was expressed in the inner retina, rather than in photoreceptors.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Eva Kiessling, Florian Peters, Lynn J. A. Ebner, Luca Merolla, Marijana Samardzija, Matthias R. Baumgartner, Christian Grimm, Sean Froese
Summary: The MMACHC gene encodes an enzyme involved in vitamin B12 metabolism. Oxidative stress may impair vitamin B12 metabolism by suppressing MMACHC expression.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Review
Neurosciences
Halit Yusuf Altay, Fatma Ozdemir, Ferdows Afghah, Zeynep Kilinc, Mehri Ahmadian, Markus Tschopp, Cavit Agca
Summary: Gene editing and gene regulatory fields are advancing, with a focus on retinal diseases in ophthalmology. Novel gene editing tools and gene regulatory approaches have the potential to overcome limitations in current gene replacement therapies and offer safer alternatives.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Duohao Ren, Sylvain Fisson, Deniz Dalkara, Divya Ail
Summary: Inherited retinal diseases are a major cause of blindness, and gene therapy using gene editing techniques like CRISPR-Cas9 shows promise for their treatment. However, ocular gene therapies can elicit immune responses that need to be managed to ensure safe and effective gene editing.
Article
Multidisciplinary Sciences
Vyara Todorova, Luca Merolla, Duygu Karademir, Gabriele M. Wogenstein, Julian Behr, Lynn J. A. Ebner, Marijana Samardzija, Christian Grimm
Summary: Understanding the physiology of the retina, particularly the highly polarized photoreceptors, is crucial for advancing our knowledge of normal vision processes and developing effective therapies for retinal degenerative diseases. However, studying the molecular mechanisms of photoreceptors is challenging due to the heterogeneity of retinal tissue and the lack of reliable cell separation methods. In this study, the researchers present a simple technique called ReLayS that successfully separates different parts of photoreceptors, enabling protein and RNA analysis. The method was validated using known proteins and genes and also revealed light-driven translocation of transducin.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Neurosciences
Afsun Sahin, Markus Tschopp, Cavit Agca
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Vyara Todorova, Mia Fee Stauffacher, Luca Ravotto, Sarah Notzli, Duygu Karademir, Lynn J. A. Ebner, Cornelia Imsand, Luca Merolla, Stefanie. M. M. Hauck, Marijana Samardzija, Aiman. S. S. Saab, L. Felipe Barros, Bruno Weber, Christian Grimm
Summary: This study investigates the pathological mechanisms of photoreceptor (PR) degeneration during chronic activation of hypoxia-inducible factors (HIFs). The results show that PR cells have an exceptionally high glycolytic flux and the activation of HIFs slows down the cellular anabolism, leading to the shortening of rod outer segments before cell degeneration.
MOLECULAR NEURODEGENERATION
(2023)
Review
Genetics & Heredity
Divya Ail, Hugo Malki, Emilia A. Zin, Deniz Dalkara
Summary: Due to their small size and safety profiles, adeno-associated viruses (AAVs) have become the preferred vector for retinal gene therapy. However, there are challenges such as limited packaging capacity, difficulties in crossing retinal barriers, and potential immune responses. This review focuses on the use of AAV in clinical trials for retinal diseases and strategies to overcome immune responses.
APPLICATION OF CLINICAL GENETICS
(2023)
Article
Multidisciplinary Sciences
Divya Ail, Diane Nava, In Pyo Hwang, Elena Brazhnikova, Celine Nouvel-Jaillard, Alexandre Dentel, Corentin Joffrois, Lionel Rousseau, Julie Degardin, Stephane Bertin, Jose-Alain Sahel, Olivier Goureau, Serge Picaud, Deniz Dalkara
Summary: To test novel therapies, suitable nonhuman primate models are needed, but there is a lack of relevant macaque models of retinal degeneration. Researchers have generated three distinct inducible cynomolgus macaque models of retinal degeneration to address this issue. Among the three models, the CRISPR-Cas9-based approach is the most advantageous for recapitulating disease-specific features and ease of implementation. The acute model, on the other hand, degenerates the fastest and is the most relevant for testing end-stage vision restoration therapies.