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
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)
Review
Cell Biology
Gregory J. Konar, Claire Ferguson, Zachary Flickinger, Matthew R. Kent, James G. Patton
Summary: The study has identified the genetic pathways and components required for retina regeneration, as well as the key regulatory events controlling the process. Muller glia are reprogrammed as adult retinal stem cells, while miRNAs are recognized as key gene regulatory molecules in controlling retina regeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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
Cell Biology
Raquel Lourenco, Ana S. Brandao, Jorge Borbinha, Rita Gorgulho, Antonio Jacinto
Summary: This study demonstrates that Yap plays a crucial role in regulating Muller glia response to injury, promoting cell cycle reentry and progenitor cell formation, leading to the differentiation of new photoreceptors in zebrafish retina regeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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
Neurosciences
Annelies Van Dyck, Ilse Bollaerts, An Beckers, Sophie Vanhunsel, Nynke Glorian, Jessie van Houcke, Tjakko J. van Ham, Lies De Groef, Lien Andries, Lieve Moons
Summary: The study demonstrates that inducing intraocular inflammation can promote axonal regrowth after optic nerve injury in zebrafish. Additionally, acute depletion of microglia and macrophages in the retina compromises optic nerve regeneration, highlighting the importance of altered glial cell interactions in the regenerative process.
Article
Neurosciences
Cuiping Zhou, Xiaoli Zhang, Yuxi Chen, Zihao Lin, Shuqiang Zhang, Zhiqiang Zhang, Lining Cao, Huaijin Guan, Jianfeng Lu, Hui Xu
Summary: Inflammation plays a complex and context-dependent role in retinal regeneration in fish. Different types of immune cells and levels of inflammatory cytokines are present in different retinal regeneration models. Proper levels of inflammation promote the reprogramming and cell cycle re-entry of Muller glia, while excessive inflammation suppresses cell proliferation.
MOLECULAR NEUROBIOLOGY
(2022)
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
Cell Biology
Patrick Boyd, Leah J. Campbell, David R. Hyde
Summary: Zebrafish have the ability to regenerate lost neurons in the retina, which is mediated by Muller glia that divide and produce neuronal precursor cells. The early signals that induce this response are not well understood. Alternative ligands of the Ciliary neurotrophic factor receptor (CNTFR), such as Cardiotrophin-like cytokine factor 1 (Clcf1) and Cytokine receptor-like factor 1a (Crlf1a), are expressed in Muller glia of the light-damaged retina. These ligands are required for Muller glia proliferation in the damaged retina and have a neuroprotective effect. CLCF1/CRLF1 injection protects against rod photoreceptor cell death and induces rod precursor cell proliferation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Neurosciences
Leah J. Campbell, Joshua S. Hobgood, Meng Jia, Patrick Boyd, Rebecca I. Hipp, David R. Hyde
Summary: The negative regulation of Muller glia proliferation in zebrafish retinal regeneration is mediated by Notch3 and DeltaB.
Article
Cell Biology
Raquel R. Martins, Mazen Zamzam, Dhani Tracey-White, Mariya Moosajee, Ryan Thummel, Catarina M. Henriques, Ryan B. MacDonald
Summary: Ageing affects the regenerative capacity of Müller glia cells in the retina, but is insufficient to stimulate neurodegeneration. Müller glia cells undergo morphological aberrations and loss of vision with ageing.
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)
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)
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
Multidisciplinary Sciences
Thanh Hoang, Jie Wang, Patrick Boyd, Fang Wang, Clayton Santiago, Lizhi Jiang, Sooyeon Yoo, Manuela Lahne, Levi J. Todd, Meng Jia, Cristian Saez, Casey Keuthan, Isabella Palazzo, Natalie Squires, Warren A. Campbell, Fatemeh Rajaii, Trisha Parayil, Vickie Trinh, Dong Won Kim, Guohua Wang, Leah J. Campbell, John Ash, Andy J. Fischer, David R. Hyde, Jiang Qian, Seth Blackshaw
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
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
Multidisciplinary Sciences
Levi Todd, Wesley Jenkins, Connor Finkbeiner, Marcus J. Hooper, Phoebe C. Donaldson, Marina Pavlou, Juliette Wohlschlegel, Norianne Ingram, Fred Rieke, Thomas A. Reh
Summary: Many neurodegenerative diseases cause the degeneration of specific types of neurons. While neurons in the adult mammalian central nervous system cannot be regenerated, glial cells in nonmammalian vertebrates can spontaneously reprogram into neural progenitors and replace damaged neurons. In this study, researchers successfully stimulated the regeneration of functional neurons in the adult mouse retina by overexpressing certain transcription factors in Müller glia cells.
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)
Meeting Abstract
Ophthalmology
Thanh Hoang, Jie Wang, Patrick Boyd, Fang Wang, Clayton Santiago, John D. Ash, Andy J. Fischer, David R. Hyde, Jiang Qian, Seth Blackshaw
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Article
Ophthalmology
He-Yan Li, Li Dong, Xu-Han Shi, Rui-Heng Zhang, Wen-Da Zhou, Hao-Tian Wu, Chu-Yao Yu, Yi-Tong Li, Yi-Fan Li, Jost B. Jonas, Wen-Bin Wei, Yue-Ming Liu
Summary: This study aimed to examine the intraocular tolerability of cetuximab when applied intravitreally, and its effect on axial elongation. The results showed that intravitreal injections of cetuximab could reduce axial elongation in a dose-dependent and number of treatment-dependent manner, without causing intraocular toxic effects.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
James D. Cole, John A. McDaniel, Joelle Nilak, Ashley Ban, Carlos Rodriguez, Zuhaad Hameed, Marta Grannonico, Peter A. Netland, Hu Yang, Ignacio Provencio, Xiaorong Liu
Summary: Aniridia is a panocular condition characterized by the loss of iris, caused mainly by mutations in the PAX6 gene. This study assessed the effects of Pax6-haploinsufficiency on retinal morphology and vision in Pax6Sey mice. The results showed elevated intraocular pressure and declining visual acuity in Pax6Sey mice, along with local retinal damage and a possible neuroinflammatory response.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
Subao Jiang, Ning Xia, Francesco Buonfiglio, Elsa W. Boehm, Qi Tang, Norbert Pfeiffer, Dominik Olinger, Huige Li, Adrian Gericke
Summary: This study found that a high-fat diet induces endothelial dysfunction in the ophthalmic artery, leading to impaired vascular function in the eye. The high-fat diet triggers oxidative stress and involves RAGE and NOX2.
EXPERIMENTAL EYE RESEARCH
(2024)
Review
Ophthalmology
Mala Upadhyay, Vera L. Bonilha
Summary: The sodium iodate (NaIO3) model is a valuable tool in studying dry AMD and evaluating the retinal structure. Through extensive research, it has been found that the death of RPE cells caused by NaIO3 injection is closely related to vision loss in patients with dry AMD. Therefore, studying NaIO3 can provide insights into the mechanisms of RPE and photoreceptor cell death and contribute to understanding RPE degeneration in AMD.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
Vicki Chrysostomou, Katharina C. Bell, Sze Woei Ng, Samyuktha Suresh, Gayathri Karthik, Marion Millet, Yingying Chung, Jonathan G. Crowston
Summary: We present a new experimental model for inducing retinal ganglion cell (RGC) dysfunction and degeneration in mice. This model allows for the reliable induction of RGC dysfunction and loss, with the resilience of the optic nerve being dependent on the age of the animal. The time-defined nature of the functional and structural changes observed in this model will facilitate the study of glial responses and the evaluation of neuroprotective treatments after intraocular pressure (IOP) injury.
EXPERIMENTAL EYE RESEARCH
(2024)
