☆ 4.7 Review

Regenerative Strategies for Retinal Neurons: Novel Insights in Non-Mammalian Model Organisms

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Biochemistry & Molecular Biology

The Role of Inflammation in Retinal Neurodegeneration and Degenerative Diseases

Geetika Kaur et al.

Summary: Retinal neurodegeneration, commonly manifested as apoptosis or impaired function of photoreceptors, is a major cause of irreversible vision loss and blindness. This review summarizes the extensive research conducted on the pathogenesis and treatment of retinal degenerative diseases, including age-related macular degeneration, inherited retinal dystrophies, retinitis pigmentosa, Stargardt macular dystrophy, and Leber congenital amaurosis. The role of inflammation in retinal degeneration is highlighted, and various therapeutic approaches, such as gene therapy and stem cell-based therapies, are evaluated.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Editorial Material Cell Biology

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Editorial Material Cell Biology

A Drosophila perspective on retina functions and dysfunctions

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Editorial Material Cell Biology

Optogenetic neuroregeneration

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Current and future therapeutic strategies for the treatment of retinal neurodegenerative diseases

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Editorial Material Neurosciences

Editorial: Retinal Changes in Neurological Diseases

Samridhi Sharma et al.

FRONTIERS IN NEUROSCIENCE (2022)

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Article Cell Biology

Visual Function is Gradually Restored During Retina Regeneration in Adult Zebrafish

Juliane Hammer et al.

Summary: In comparison to mammals, zebrafish have the ability to regenerate organs and tissues. This study focused on the regeneration of visual function in adult zebrafish after light-induced retinal damage. The researchers found that visual function was impaired initially, but gradually restored over time in a gradual manner, with easier visual conditions recovering earlier than more demanding conditions.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Article Cell Biology

Muller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina

Raquel R. Martins et al.

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.

AGING CELL (2022)

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Review Neurosciences

Solving neurodegeneration: common mechanisms and strategies for new treatments

Lauren K. Wareham et al.

Summary: There may be common mechanisms across neurodegenerative diseases that can lead to new therapeutic targets. A virtual meeting was organized to discuss these mechanisms and emerging treatments. The meeting focused on neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions as major areas of mechanistic overlap.

MOLECULAR NEURODEGENERATION (2022)

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Review Cell & Tissue Engineering

Stem Cell-based Treatment Strategies for Degenerative Diseases of the Retina

Deepthi S. Rajendran Nair et al.

Summary: This article reviews different stem cell-based therapies for retinal degenerative diseases, including cell replacement therapy and factor release therapy, and discusses the challenges in translating these therapies to clinical practice.

CURRENT STEM CELL RESEARCH & THERAPY (2022)

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Review Cell Biology

Critical Examination of Muller Glia-Derived in vivo Neurogenesis in the Mouse Retina

Ye Xie et al.

Summary: This article discusses the regenerative potential of Muller glia (MG) in the mouse retina, focusing on the progress made in the de novo regeneration of retinal neurons through the reprogramming of MG.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Review Neurosciences

Reprogramming neurons for regeneration: The fountain of youth

Shu-Guang Yang et al.

Summary: Neurons in the central nervous system lose their regenerative ability during maturation due to changes in transcriptomic and chromatin landscape, but can be reprogrammed back to induced pluripotent stems cells. Recent findings show that certain transcription factors can convert non-neural cells into neurons, bypassing the pluripotent stage, and promote neural regeneration. These factors can rejuvenate mature neurons through cellular state reprogramming, offering potential for regeneration.

PROGRESS IN NEUROBIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Defects of full-length dystrophin trigger retinal neuron damage and synapse alterations by disrupting functional autophagy

Elisabetta Catalani et al.

Summary: The absence of full-length dystrophin leads to structural damages and impaired autophagy in the retina, affecting neuronal survival and visual properties. Reactivation of autophagy can prevent cell death and structural changes, improving the response to light in mutant flies. Overall, functional dystrophin is crucial for synapsis stabilization and proper neuronal survival in the retina.

CELLULAR AND MOLECULAR LIFE SCIENCES (2021)

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Review Clinical Neurology

Retinal imaging in Alzheimer's and neurodegenerative diseases

Peter J. Snyder et al.

Summary: Research on retinal imaging as potential biomarkers for Alzheimer's disease and other neurodegenerative diseases has significantly increased over the past 20 years. Discussions have focused on the different modalities of retinal imaging, their strengths and weaknesses, and the importance of defining the context of use to guide the development of retinal biomarkers.

ALZHEIMERS & DEMENTIA (2021)

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Review Ophthalmology

Retina in a dish: Cell cultures, retinal explants and animal models for common diseases of the retina

Sven Schnichels et al.

Summary: The exact pathogenesis of retinal diseases like AMD, glaucoma, and DR remains unclear, and current therapeutic options are often unsatisfactory. Research heavily relies on animal models, but there is pressure to reduce animal research. Improved disease models are needed to understand pathologies and develop treatment options that require fewer or no experimental animals.

PROGRESS IN RETINAL AND EYE RESEARCH (2021)

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Article Neurosciences

Muller Glia-Mediated Retinal Regeneration

Hui Gao et al.

Summary: Muller glia play a crucial role in retinal development, with lower vertebrates having the ability for retinal regeneration. In mammals, Muller glia have limited regenerative potential, but progress has been made in reprogramming them to restore vision.

MOLECULAR NEUROBIOLOGY (2021)

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Article Neurosciences

Muller glia-myeloid cell crosstalk accelerates optic nerve regeneration in the adult zebrafish

Annelies Van Dyck et al.

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.

GLIA (2021)

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Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication

Neale J. Harrison et al.

Summary: Understanding the relationship between Drosophila neurogenesis-related genes and glial cells reveals that la-2 and Dilp-6 drive the reprogramming of glial cells into neural stem cells for regeneration.

ELIFE (2021)

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Review Cell Biology

Neurodegeneration, Neuroprotection and Regeneration in the Zebrafish Retina

Salvatore L. Stella et al.

Summary: Neurodegenerative retinal diseases lead to gradual loss of retinal neurons, requiring neuroprotective or regenerative strategies for treatment. Zebrafish, due to their similar eye structure and development to mammals, are commonly used as a model for studying these diseases.

CELLS (2021)

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Article Multidisciplinary Sciences

Stimulating and Analyzing Adult Neurogenesis in the Drosophila Central Brain

Kassi L. Crocker et al.

Summary: Adult Drosophila brain can generate new neurons and glia in response to penetrating traumatic brain injury, making it a robust model for studying neural regeneration. The powerful genetic tools and rigorous injury protocols available in Drosophila facilitate further studies into the mechanisms underlying neural regeneration.

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS (2021)

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Article Cell Biology

A novel injury paradigm in the central nervous system of adult Drosophila: molecular, cellular and functional aspects

Maria Losada-Perez et al.

Summary: The article introduces a new experimental design to damage the mammalian central nervous system through a contusion injury paradigm. It demonstrates that adult Drosophila melanogaster glial cells undergo spontaneous functional recovery after injury and analyzes the role of immune cells in functional regeneration.

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Article Cell Biology

A Comparative Analysis of Gene and Protein Expression Throughout a Full 28-Day Retinal Regeneration Time-Course in Adult Zebrafish

Ashley C. Kramer et al.

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)

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Article Pharmacology & Pharmacy

Retinal damage in a new model of hyperglycemia induced by high-sucrose diets

Elisabetta Catalani et al.

Summary: High-sucrose diets inducing hyperglycemia in fruit flies lead to eye defects, apoptosis/autophagy dysregulation, oxidative stress, and visual dysfunctions. These findings suggest that a simple in vivo model like the fruit fly can be used to study the pathophysiology of neuroretinal alterations in early stages of diabetic retinopathy.

PHARMACOLOGICAL RESEARCH (2021)

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Article Multidisciplinary Sciences

The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration

Lyndsay L. Leach et al.

Summary: Research has revealed that zebrafish RPE has strong intrinsic regenerative potential, with elements of immune response identified as critical mediators in the regeneration process. Macrophage/microglia cells are responsive to RPE damage and essential for the timely progression of regenerative response.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Genetics & Heredity

Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease

Alvaro Ingles-Prieto et al.

Summary: This study presents a novel light-based method to deliver cell type-specific pro-survival signals in a genetic model of Parkinson's disease, demonstrating significant therapeutic effects. The optogenetic delivery of trophic signals is cell type-specific and reversible, offering potential for the development of novel spatio-temporal regulation of tissue repair strategies.

PLOS GENETICS (2021)

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Article Multidisciplinary Sciences

Neural specification, targeting, and circuit formation during visual system assembly

Jennifer Malin et al.

Summary: Through studying the Drosophila visual system, researchers have uncovered principles guiding the specification and connectivity of visual system neurons, which can be broadly applicable to other systems. The focus is on how temporal and spatial patterning generates diverse cell types and guides the connection of neurons to the correct target regions.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Review Neurosciences

Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise

Fengchao Wang et al.

Summary: The limited capacity for neurogenesis in the adult mammalian brain greatly hampers neuronal regeneration, but recent discoveries of direct reprogramming of endogenous glial cells into functional neurons provide new opportunities. However, more research is needed before in situ glial cell reprogramming can be applied therapeutically.

NEUROSCIENCE BULLETIN (2021)

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Article Genetics & Heredity

Necrosis-induced apoptosis promotes regeneration in Drosophila wing imaginal discs

Jacob Klemm et al.

Summary: Regeneration is a complex process that requires a coordinated genetic response to tissue loss. Necrosis can stimulate regeneration at an equivalent level to apoptosis, but also results in significant apoptosis far from the site of ablation, termed necrosis-induced apoptosis (NiA). This programmed cell death at a distance from the injury promotes regeneration by limiting proliferation.

GENETICS (2021)

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Article Genetics & Heredity

Neurogenesis in the adult Drosophila brain

Kassi L. Crocker et al.

Summary: By studying the brain regeneration mechanisms in adult Drosophila, it has been discovered that after a traumatic brain injury, new neurons and glial cells can be generated in the Drosophila brain, leading to the repair of neural circuits and improvement in locomotor abnormalities. This indicates that adult Drosophila brains are capable of neuronal repair, which may provide insights into neural regeneration mechanisms relevant to human brain repair.

GENETICS (2021)

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Article Cell Biology

MMP2 Modulates Inflammatory Response during Axonal Regeneration in the Murine Visual System

Lien Andries et al.

Summary: Neuroinflammation can trigger axonal regrowth in the CNS, and MMP2 plays a key role in linking inflammation and axonal regeneration. MMP2 deficiency leads to reduced long-distance axonal regeneration, but this phenotype can be rescued by restoring MMP2 expression in myeloid cells. Additionally, MMP2 deficiency affects the coordinated expression of pro- and anti-inflammatory molecules, showcasing a new mechanism by which MMP2 facilitates axonal regeneration.

CELLS (2021)

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Review Cell Biology

Insights on the Regeneration Potential of Muller Glia in the Mammalian Retina

Ahmed Salman et al.

Summary: Muller glia play crucial roles in maintaining retinal homeostasis and have regenerative potential in fish and mammals. While they can adopt stem cell characteristics in mammals, their native regeneration potential is limited. Further studies are needed to explore the potential of Muller glia as a source for cell regeneration therapy in humans.

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Article Biochemistry & Molecular Biology

Nutraceutical Strategy to Counteract Eye Neurodegeneration and Oxidative Stress in Drosophila melanogaster Fed with High-Sugar Diet

Elisabetta Catalani et al.

Summary: The study evaluated the beneficial and antioxidant properties of food supplementation with Lisosan G in a fruit fly model of hyperglycemia-induced retinal damage, finding positive effects on the visual system, apoptosis reduction, and activation of protective autophagy. Lisosan G also decreased levels of ROS and peroxynitrite, and impacted key oxidative stress-related metabolites, providing robust antioxidant effects on retinal neurons and efficacious neuroprotection of hyperglycemic eye.

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Review Ophthalmology

Glaucoma as Neurodegeneration in the Brain

Jane W. Chan et al.

Summary: Glaucoma is a progressive neurodegenerative disorder characterized by optic nerve degeneration, which shares common neurodegenerative pathways with Alzheimer's disease and other tauopathies. Genetic associations, such as the Apolipoprotein E gene, have been found in both primary open angle glaucoma and Alzheimer's disease, suggesting potential overlap in pathogenic mechanisms. Neuronal pathways contributing to transsynaptic neurodegeneration in Alzheimer's disease and tauopathies may also play a role in glaucomatous neurodegeneration.

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Review Ophthalmology

Retinal stem cell transplantation: Balancing safety and potential

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Model systems for regeneration: Drosophila

Donald T. Fox et al.

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Glial Metabolic Rewiring Promotes Axon Regeneration and Functional Recovery in the Central Nervous System

Feng Li et al.

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Drosophila miR-87 promotes dendrite regeneration by targeting the transcriptional repressor Tramtrack69

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Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila

Qin Wang et al.

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Organ Cultures for Retinal Diseases

Jose Hurst et al.

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Kynurenine Metabolism in the Fat Body Non-autonomously Regulates Imaginal Disc Repair in Drosophila

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The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

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Retinal Organ Cultures as Alternative Research Models

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Dynamic changes in microglial and macrophage characteristics during degeneration and regeneration of the zebrafish retina

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Drosophila as a Model System to Study Cell Signaling in Organ Regeneration

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Analysis of DNA methylation reveals a partial reprogramming of the Muller glia genome during retina regeneration

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