Article
Neurosciences
Isabella Palazzo, Levi J. Todd, Thanh V. Hoang, Thomas A. Reh, Seth Blackshaw, Andy J. Fischer
Summary: Muller glia (MG) in mammalian retinas are incapable of regenerating neurons after damage, whereas the MG in lower vertebrates regenerate functional neurons. Identification of cell signaling pathways and gene regulatory networks that regulate MG-mediated regeneration is key to harnessing the regenerative potential of MG. In this study, NFkB signaling was found to play a crucial role in regulating immune cell accumulation and suppressing the neurogenic potential of MG after damage. Inhibition of NFkB enhanced the reprogramming of MG into neuron-like cells. Additionally, TGF beta 2 signaling and suppression of NFI and Id transcription factors were coordinated with NFkB signaling to regulate MG-mediated regeneration.
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
Ophthalmology
Aya Motoyoshi, Fuminori Saitoh, Tomohiro Iida, Hiroki Fujieda
Summary: The proliferative and neurogenic potential of retinal Muller glia after injury varies widely across species. This study reveals that nestin plays a critical role in regulating the proliferative response of rat Muller glia after retinal injury, while this response is not observed in mice. The findings highlight the importance of cross species analysis to understand the molecular mechanisms of injury response in the mammalian retina.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Neurosciences
Whitney A. Thiel, Zachary Blume, Diana M. Mitchell
Summary: This study found that microglia are primarily responsible for the clearance of dying cells in the developing zebrafish retina, while Muller glia also have a limited role in this process. In the absence of microglia, Muller glia significantly increase their uptake of apoptotic cells, with several of these cells localized with the early phagosome/endosome marker Rab5. Additionally, lysosomal staining also increases in Muller glia in the absence of microglia. These findings highlight the phagocytic capacity and compensatory functions of Muller glia, and emphasize the need to consider the effects of microglial deficiency or depletion on other glial cell types.
Article
Cell Biology
Maria Iribarne, David R. Hyde
Summary: This study investigated the role of microglia in zebrafish retinal regeneration after damage. The researchers found that acute and chronic damage led to different inflammation profiles and regeneration outcomes. Understanding the differences could provide valuable insights for improving therapeutic strategies for repairing injured mammalian tissues.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Seung-Hee Lee, Yong-Soo Park, Sun-Sook Paik, In-Beom Kim
Summary: The study found that RD leads to changes in the entire retinal region, including photoreceptor cell death, gradual decrease in the outer nuclear layer, and increased glial response, indicating the need for further understanding of the effects of RD on the border and intact retinal regions.
Article
Neurosciences
Wei Wei, Piaopiao Hu, Mengqi Qin, Guiping Chen, Feifei Wang, Shengrui Yao, Ming Jin, Zhi Xie, Xu Zhang
Summary: SIRT4 is highly expressed in retinal Muller glial cells and is relevant to the expression of GS. SIRT4 does not appear to be essential in retinal development, but resveratrol, as an activator of SIRT4, can upregulate GS protein expression and protect the retina.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Sergi Angel Bonilla-Pons, Shoma Nakagawa, Elena Garreta Bahima, Alvaro Fernandez-Blanco, Martina Pesaresi, Justin Christopher D'Antin, Ruben Sebastian-Perez, Daniela Greco, Eduardo Dominguez-Sala, Raul Gomez-Riera, Rafael Ignacio Barraquer Compte, Mara Dierssen, Nuria Montserrat Pulido, Maria Pia Cosma
Summary: This study discovered that cell fusion can occur between human müller glia and adult stem cells in the human retina, resulting in partial regeneration of neurons. The results suggest that cell fusion-mediated therapy may be a potential regenerative approach for treating human retinal dystrophies.
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
Neurosciences
Evin Magner, Pamela Sandoval-Sanchez, Ashley C. Kramer, Ryan Thummel, Peter F. Hitchcock, Scott M. Taylor
Summary: The study reveals that disruption of miR-18a plays a critical role in injury-induced photoreceptor regeneration in zebrafish, affecting proliferation, inflammation response, and cell migration.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Una Greferath, Mario Huynh, Andrew Ian Jobling, Kirstan Anne Vessey, Gene Venables, Denver Surrao, Helen Christine O'Neill, Ioannis J. Limnios, Erica Lucy Fletcher
Summary: Retinitis pigmentosa is a group of inherited retinal degenerations characterized by gradual loss of photoreceptors, ultimately leading to irreversible vision loss. This study focused on analyzing the changes in glial, microglial, and photoreceptor cells in different retinal locations in RCS rats, revealing significant differences in photoreceptor loss between the dorsal and ventral retina. The findings suggest that breakdown of the outer limiting membrane may play a role in exacerbating photoreceptor loss in the ventral retina, highlighting the value of using the RCS rat model for sectorial retinitis pigmentosa.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Ophthalmology
Ke Ning, Brent E. Sendayen, Tia J. Kowal, Biao Wang, Bryan W. Jones, Yang Hu, Yang Sun
Summary: Through studying the inner nuclear layer of retinas in mice and rhesus macaque primates, it was found that several subpopulations of amacrine cells form cilia during early retinal development.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Cell Biology
Ashley C. Kramer, Katherine Gurdziel, Ryan Thummel
Summary: The study revealed that adult zebrafish have the ability to completely regenerate their retinas through the re-entry of Muller glia into the cell cycle and differentiation into new photoreceptors after intense light exposure. Additionally, the research identified two peaks of MG gliosis, a distinct transcriptional shift between 5- and 10-days post lesion, and different patterns of transcriptional recovery of photoreceptor opsins at 28 days post lesion.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(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
Neurosciences
Deborah S. Lew, Morgan J. McGrath, Silvia C. Finnemann
Summary: The research shows that extracellular galectin-3 and protein S can promote clearance phagocytosis by Muller cells, with MERTK receptor playing a role in this process. Lack of galectin-3 leads to increased activation of Muller cells and exacerbation of retinal damage.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Developmental Biology
Isabella Palazzo, Kyle Deistler, Thanh Hoang, Seth Blackshaw, Andy J. Fischer
Article
Oncology
Timothy W. Grosel, Matthew Karl, Robert T. Pilarski, Frederick H. Davidorf, Mohamed H. Abdel-Rahman, Colleen M. Cebulla
Summary: This report highlights a case of an atypical choroidal nevus in a patient with a pathogenic PALB2 germline variant, suggesting a potential risk factor for uveal melanocytic neoplasms. Further assessment of prevalence and progression in PALB2 variant carriers is warranted.
Article
Neurosciences
Kristina G. Witcher, Chelsea E. Bray, Titikorn Chunchai, Fangli Zhao, Shane M. O'Neil, Alan J. Gordillo, Warren A. Campbell, Daniel B. McKim, Xiaoyu Liu, Julia E. Dziabis, Ning Quan, Daniel S. Eiferman, Andy J. Fischer, Olga N. Kokiko-Cochran, Candice Askwith, Jonathan P. Godbout
Summary: Traumatic brain injury can lead to significant neuropsychiatric problems and neurodegenerative pathologies that last for years. This study showed that microglia play a crucial role in acute and chronic stages of TBI, influencing inflammation and neuropathology development, which in turn affect neuronal homeostasis and behavioral outcomes.
JOURNAL OF NEUROSCIENCE
(2021)
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
Hoda Zeinab M. Amer, Colleen M. Cebulla, Zaibo Li, Rulong Shen
Summary: Intraocular metastases from the lung are a common differential diagnosis for cytopathologists reading fine needle aspiration biopsies, especially challenging when there is no previous lung cancer diagnosis. Thorough metastatic workup and ancillary testing ensure an accurate diagnosis.
Article
Neurosciences
Warren A. Campbell, Sydney Blum, Alana Reske, Thanh Hoang, Seth Blackshaw, Andy J. Fischer
Summary: The study investigated the role of endocannabinoids in the transition of Muller glia cells and the formation of retinal cells, finding that endocannabinoids influence the reactivity of MG and the formation of MGPCs but do not affect immune cells in the retina.
Article
Developmental Biology
Warren A. Campbell, Allen Tangeman, Heithem M. El-Hodiri, Evan C. Hawthorn, Maddie Hathoot, Sydney Blum, Thanh Hoang, Seth Blackshaw, Andy J. Fischer
Summary: A recent study on chick retinas found that fatty acid binding proteins (FABPs) are highly expressed and play a role in regulating the function of glial cells and microglia. Inhibition of FABPs leads to transitions of glial cells to reactive states and suppresses the formation of progenitor cells, while inhibition of fatty acid synthase (FASN) increases microglia proliferation and suppresses progenitor cell formation.
Article
Neurosciences
Heithem M. El-Hodiri, Warren A. Campbell, Lisa E. Kelly, Evan C. Hawthorn, Maura Schwartz, Archana Jalligampala, Maureen A. McCall, Kathrin Meyer, Andy J. Fischer
Summary: The regenerative potential of Muller glia varies across species, with fish showing extraordinary potential and mammals showing limited potential. NFIs are identified as cell-intrinsic factors that suppress the neurogenic potential of MGPCs in the chick retina, and their expression patterns in developing and mature retinas have been characterized.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Neurosciences
Isabella Palazzo, Levi J. Todd, Thanh V. Hoang, Thomas A. Reh, Seth Blackshaw, Andy J. Fischer
Summary: Muller glia (MG) in mammalian retinas are incapable of regenerating neurons after damage, whereas the MG in lower vertebrates regenerate functional neurons. Identification of cell signaling pathways and gene regulatory networks that regulate MG-mediated regeneration is key to harnessing the regenerative potential of MG. In this study, NFkB signaling was found to play a crucial role in regulating immune cell accumulation and suppressing the neurogenic potential of MG after damage. Inhibition of NFkB enhanced the reprogramming of MG into neuron-like cells. Additionally, TGF beta 2 signaling and suppression of NFI and Id transcription factors were coordinated with NFkB signaling to regulate MG-mediated regeneration.
Article
Multidisciplinary Sciences
Faith H. Brennan, Yang Li, Cankun Wang, Anjun Ma, Qi Guo, Yi Li, Nicole Pukos, Warren A. Campbell, Kristina G. Witcher, Zhen Guan, Kristina A. Kigerl, Jodie C. E. Hall, Jonathan P. Godbout, Andy J. Fischer, Dana M. McTigue, Zhigang He, Qin Ma, Phillip G. Popovich
Summary: This study demonstrates that microglia are necessary for optimal repair after murine spinal cord injury (SCI) using microglia-specific depletion techniques and single cell transcriptomics.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Isabella Palazzo, Lisa Kelly, Lindsay Koenig, Andy J. Fischer
Summary: In this study, the researchers investigated different cytokines, growth factors, cell signaling pathways, and damage paradigms that influence NFkB-signaling in the mouse retina. They found that exogenous TNF and IL1 beta can activate NFkB-signaling in Muller glia in undamaged retinas. They also discovered that TLR1/2 agonist indirectly activates NFkB-signaling in Muller glia, but this activation depends on the presence of microglia.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Neurosciences
Warren A. Campbell, Heithem M. El-Hodiri, Diego Torres, Evan C. Hawthorn, Lisa E. Kelly, Leo Volkov, David Akanonu, Andy J. Fischer
Summary: Chromatin access and epigenetic gene silencing play important roles in regulating gene expression during developmental processes. This study investigates the expression and functions of S-adenosylhomocysteine hydrolase (SAHH) and histone methyltransferases (HMTs) in the formation of Muller glia-derived progenitor cells (MGPCs) in chick and mouse retinas. In chick, inhibition of SAHH blocks the formation of MGPCs by reducing H3K27me3 levels, while in the mouse retina, SAHH inhibition has no effect on neuron-like cell differentiation. These findings suggest that SAHH and HMTs are required for the reprogramming of MG into MGPCs in chick retinas.
Meeting Abstract
Ophthalmology
Isabella Palazzo, Levi Todd, Thanh V. Hoang, Thomas Reh, Seth Blackshaw, Andy J. Fischer
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Meeting Abstract
Ophthalmology
Olivia Taylor, Andy J. Fischer
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Meeting Abstract
Ophthalmology
Heithem M. El-Hodiri, Warren Campbell, Diego Torres, Evan C. Hawthorn, Lisa E. Kelly, Leo Volkov, Andy J. Fischer
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Neurosciences
Wenzhu Wang, Zihan Li, Yitong Yan, Shuo Wu, Xinyu Yao, Chen Gao, Lanxiang Liu, Yan Yu
Summary: This study investigated the reparative mechanisms of low-intensity pulsed ultrasound (LIPUS) in traumatic brain injury (TBI) and found that LIPUS promotes hippocampal neurogenesis, enhances neural electrical activity and neural plasticity, ultimately restoring neuronal function and cognitive capabilities in TBI mice.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Wenmin Yi, Fei Chen, Minghao Yuan, Chuanling Wang, Shengyuan Wang, Jie Wen, Qian Zou, Yinshuang Pu, Zhiyou Cai
Summary: The study suggests that a high-fat diet may lead to tau hyperphosphorylation and synaptic dysfunction by inhibiting the SIRT1/AMPK pathway and disrupting autophagy flux, ultimately resulting in cognitive decline.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Kim M. Hemsley, Helen Beard, Glyn Chidlow, Teresa Mammone, Leanne K. Winner, Daniel Neumann, Barbara King, Marten F. Snel, Paul J. Trim, Robert J. Casson
Summary: Optical coherence tomography (OCT) is a non-invasive method that can be used to rapidly and quantitatively examine the integrity of the neuroretina. It has been shown that OCT can be used to observe retinal thinning in patients with childhood dementia, and to assess the improvement of retinal structure after treatment. Furthermore, OCT can provide insights into other childhood dementias based on the correlation between retinal and brain degeneration in Sanfilippo syndrome.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Qianling Jiang, Xin Ma, Gaochen Zhu, Wen Si, Lingyu He, Guan Yang
Summary: This study investigated the effects of EAE induction on thymopoiesis and T cell development, revealing changes such as increased apoptosis, decreased proliferation, and a blockade in the transition from double-negative thymocytes to double-positive cells. It was also found that positive selection was disrupted in the thymus of EAE mice, along with an increased production of regulatory T cells.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Alice McDouall, Guido Wassink, Sumudu Ranasinghe, Kelly Q. Zhou, Rashika N. Karunasinghe, Justin M. Dean, Joanne O. Davidson
Summary: This study found that blocking connexin 43 hemichannels can attenuate brain injury and promote neurodevelopment in infants with mild hypoxic-ischemic encephalopathy, without causing hypothermia.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Hannah Sweetman, Mahmudur Rahman, Aditya Vedantam, Kajana Satkunendrarajah
Summary: Degenerative cervical myelopathy (DCM) is a neurological condition characterized by chronic compression of the cervical spinal cord, leading to impaired limb function. While respiratory dysfunction is not a common symptom of DCM, it can affect the ventilatory response to respiratory challenges. Surgical decompression improves sensorimotor function in DCM, but its impact on respiratory function is unclear. This study evaluates respiratory function and adaptive ventilation in a DCM model, showing that DCM impairs acute adaptive ventilatory ability and surgical decompression does not fully restore it.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Chengmei Sun, Muhammad Saif Ur Rahman, Budbazar Enkhjargal, Jianhua Peng, Keren Zhou, Zhiyi Xie, Lingyun Wu, Tongyu Zhang, Qiquan Zhu, Jiping Tang, Yujia Zeng, John H. Zhang, Shanshan Xu
Summary: This study found that Osteopontin (OPN) can attenuate inflammatory responses after subarachnoid hemorrhage (SAH) by promoting an anti-inflammatory microglial state. This effect may be mediated through the integrin-FAK-STAT3 and NF-kappa B signaling pathways.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Yang Yang, Xuezhu Chen, Chuanyan Yang, Mei Liu, Qianying Huang, Likun Yang, Yuhai Wang, Hua Feng, Zhongyang Gao, Tunan Chen
Summary: The study explores the effects of specific chemogenetic stimulation of intact corticospinal tract on functional recovery after stroke in mice. The findings demonstrate that combining chemogenetic activation with rehabilitation training leads to significant motor functional recovery by promoting axon sprouting and rewiring new functional circuits.
EXPERIMENTAL NEUROLOGY
(2024)