Engineering an in vitro retinothalamic nerve model DOI Creative Commons

Giulia Amos,

Stephan J. Ihle, Blandine Clément

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: May 21, 2024

Understanding the retinogeniculate pathway in vitro can offer insights into its development and potential for future therapeutic applications. This study presents a Polydimethylsiloxane-based two-chamber system with axon guidance channels, designed to replicate unidirectional signal transmission . Using embryonic rat retinas, we developed model where retinal spheroids innervate thalamic targets through up 6 mm long microfluidic channels. combination of electrical stimulation functional calcium imaging assessed how channel length frequency affects target response. In presented integrated 20 identical retinothalamic neural networks aligned on single transparent microelectrode array, enhancing robustness quality recorded data. We found that network integrity depends length, 0.5–2 channels maintaining over 90% morphological 50% integrity. A reduced was longer The results indicate notable reduction forward spike propagation than 4 mm. Additionally, conduction fidelity decreased increasing length. Yet, stimulation-induced activity remained unaffected by Finally, sustained response could be elicited frequencies 31 Hz, higher leading transient responses. conclusion, this high-throughput platform demonstrates retina brain formation

Language: Английский

Solving neurodegeneration: common mechanisms and strategies for new treatments DOI Creative Commons
Lauren K. Wareham, Shane A. Liddelow, Sally Temple

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: March 21, 2022

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology site disease pathology. To address these and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus the Melza M. Frank Theodore Barr Foundation collaborated to bring together key opinion leaders experts field for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style focused uncovering mechanistic roots promising new catalyzed by goal finding treatments glaucoma, world's leading cause irreversible blindness interest three hosting foundations. Glaucoma, which causes vision loss through degeneration optic nerve, likely shares early cellular molecular events with other diseases central nervous system. Here we major areas overlap between system: neuroinflammation, bioenergetics metabolism, genetic contributions, neurovascular interactions. We summarize important discussion points emphasis research that are most innovative treatment neurodegeneration yet require further development. The is highlighted provides unique opportunities collaboration will lead efforts preventing ultimately loss.

Language: Английский

Citations

193
Glaucoma: now and beyond DOI
Hari Jayaram, Miriam Kolko, David S. Friedman

et al.

The Lancet, Journal Year: 2023, Volume and Issue: 402(10414), P. 1788 - 1801

Published: Sept. 21, 2023

Language: Английский

Citations

157
Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells DOI Creative Commons
Anne Jacobi, Nicholas M. Tran, Wenjun Yan

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(16), P. 2625 - 2645.e7

Published: June 28, 2022

Language: Английский

Citations

107
The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases DOI Creative Commons
Kun‐Che Chang, Pei‐Feng Liu, Chia‐Hsuan Chang

et al.

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: Jan. 3, 2022

Oxidative stress is mainly caused by intracellular reactive oxygen species (ROS) production, which highly associated with normal physiological homeostasis and the pathogenesis of diseases, particularly ocular diseases. Autophagy a self-clearance pathway that removes oxidized cellular components regulates ROS levels. can modulate autophagy activity through transcriptional posttranslational mechanisms. further triggers transcription factor activation degrades impaired organelles proteins to eliminate excessive in cells. Thus, may play an antioxidant role protecting cells from oxidative stress. Nevertheless, cause autophagic cell death. In this review, we summarize mechanisms interaction between their roles several including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), optic nerve atrophy, are major causes blindness. The modulators used treat diseases discussed. findings studies reviewed here might shed light on development use for future treatment

Language: Английский

Citations

104
Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells DOI Creative Commons
Feng Tian, Yuyan Cheng, Songlin Zhou

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(16), P. 2607 - 2624.e8

Published: June 28, 2022

Language: Английский

Citations

90
Advancing cell therapy for neurodegenerative diseases DOI Creative Commons
Sally Temple

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(5), P. 512 - 529

Published: April 20, 2023

Language: Английский

Citations

90
Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia DOI Creative Commons
Jing Wang, Xuelian He, Huyan Meng

et al.

Neuron, Journal Year: 2020, Volume and Issue: 108(5), P. 876 - 886.e4

Published: Oct. 26, 2020

Language: Английский

Citations

102
Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes DOI Creative Commons
Liang Li, Fang Fang, Xue Feng

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(16), P. 2646 - 2663.e6

Published: Aug. 1, 2022

Language: Английский

Citations

42
Temporal single-cell atlas of non-neuronal retinal cells reveals dynamic, coordinated multicellular responses to central nervous system injury DOI
Inbal Benhar, Jiarui Ding, Wenjun Yan

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(4), P. 700 - 713

Published: Feb. 20, 2023

Language: Английский

Citations

33
Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium DOI Creative Commons
Jonathan R. Soucy,

Erika A. Aguzzi,

Julie Cho

et al.

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Sept. 21, 2023

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach reverse from if newly introduced neurons can reestablish functional retinal thalamic circuits. In theory, RGCs might be repopulated through transplantation of stem cell-derived or via induction endogenous transdifferentiation. The Repopulation, Stem Cell Transplantation, Optic Nerve Regeneration (RReSTORe) Consortium was established address challenges associated with repair visual pathway neuropathy. 2022, RReSTORe initiated ongoing international collaborative discussions advance field has identified five critical areas focus: (1) development differentiation, (2) Transplantation methods models, (3) survival, maturation, host interactions, (4) Inner wiring, (5) Eye-to-brain connectivity. Here, we discuss most pertinent questions that exist on path clinical translation suggest experimental directions propel this work going forward. Using these subtopic discussion groups (SDGs) as framework, multidisciplinary approaches restore diseased by leveraging groundbreaking insights developmental neuroscience, biology, molecular optical imaging, animal models neuropathy, immunology & immunotolerance, neuropathology neuroprotection, materials science biomedical engineering, neuroscience. While significant hurdles remain, Consortium's efforts provide comprehensive roadmap for advancing hold potential transformative progress restoring patients suffering neuropathies.

Language: Английский

Citations

31