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

Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact DOI

Kenichi Toma,

Mengya Zhao, Shaobo Zhang

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2767 - 2784.e23

Published: May 1, 2024

Language: Английский

Citations

12
Generating and Using Transcriptomically Based Retinal Cell Atlases DOI Creative Commons
Karthik Shekhar, Joshua R. Sanes

Annual Review of Vision Science, Journal Year: 2021, Volume and Issue: 7(1), P. 43 - 72

Published: July 6, 2021

It has been known for over a century that the basic organization of retina is conserved across vertebrates. equally clear retinal cells can be classified into numerous types, but only recently have methods devised to explore this diversity in unbiased, scalable, and comprehensive ways. Advances high-throughput single-cell RNA sequencing (scRNA-seq) played pivotal role effort. In article, we outline experimental computational components scRNA-seq review studies used them generate atlases cell types several vertebrate species. These enabled development, responses injury, expression patterns genes implicated disease, evolution types. Recently, inquiry expanded include entire eye visual centers brain. enhanced our understanding function dysfunction provided tools insights exploring neural throughout

Language: Английский

Citations

52
Exosome-Mediated Delivery of the Neuroprotective Peptide PACAP38 Promotes Retinal Ganglion Cell Survival and Axon Regeneration in Rats With Traumatic Optic Neuropathy DOI Creative Commons
Tian Wang, Yiming Li, Miao Guo

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: April 6, 2021

Traumatic optic neuropathy (TON) refers to nerve damage caused by trauma, leading partial or complete loss of vision. The primary treatment options, such as hormonal therapy and surgery, have limited efficacy. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), a functional endogenous neuroprotective peptide, has emerged promising therapeutic agent. In this study, we used rat retinal ganglion cell (RGC) exosomes nanosized vesicles for the delivery PACAP38 loaded via exosomal anchor peptide CP05 (EXO ). EXO showed greater uptake efficiency in vitro vivo than PACAP38. results that significantly enhanced RGC survival rate fiber layer thickness TON model. Moreover, promoted axon regeneration function after injury. These findings indicate can be option may implications patients with TON.

Language: Английский

Citations

46
CXCL5/CXCR2 modulates inflammation-mediated neural repair after optic nerve injury DOI
Yu‐Fen Liu,

Jiajian Liang,

Tsz Kin Ng

et al.

Experimental Neurology, Journal Year: 2021, Volume and Issue: 341, P. 113711 - 113711

Published: March 27, 2021

Language: Английский

Citations

41
Activating Transcription Factor 3 (ATF3) is a Highly Conserved Pro-regenerative Transcription Factor in the Vertebrate Nervous System DOI Creative Commons
Hilary R. Katz,

Anthony A. Arcese,

Ona Bloom

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: March 8, 2022

The vertebrate nervous system exhibits dramatic variability in regenerative capacity across species and neuronal populations. For example, while the mammalian central (CNS) is limited its capacity, CNS of many other vertebrates readily regenerates after injury, as does peripheral (PNS) mammals. Comparing molecular responses tissues can therefore provide valuable insights into both conserved distinct mechanisms successful regeneration. One gene that emerging a pro-regenerative factor activating transcription 3 (ATF3), which has long been associated with tissue trauma. A growing number studies indicate ATF3 may actively promote axon regrowth regeneration ranging from lampreys to Here, we review data on structural functional conservation protein species. RNA expression exhibit different abilities regenerate their following traumatic nerve injury reveals consistently induced neurons within first few days injury. Genetic deletion or knockdown shown mouse zebrafish, respectively, reduce regeneration, inducing promotes sprouting, regrowth, Thus, propose be an evolutionarily regulator Identifying downstream effectors will critical next step understanding basis

Language: Английский

Citations

34
Osteopontin drives retinal ganglion cell resiliency in glaucomatous optic neuropathy DOI Creative Commons
Mengya Zhao,

Kenichi Toma,

Benyam Kinde

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113038 - 113038

Published: Aug. 23, 2023

Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions the injury model. Among major RGC subclasses, αRGCs intrinsically photosensitive RGCs (ipRGCs) preferentially survive conditions, similar findings in retina subject axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found ectopic neuronal expression of (Spp1) other conditions. This contrasted with Spp1 downregulation αRGC-specific elimination led significant loss, diminishing their resiliency. overexpression robust neuroprotection susceptible subclasses under In contrast, did not significantly protect Additionally, SPP1 marked adult human subsets large somata aqueous humor correlated glaucoma severity. Our study reveals Spp1's role mediating resiliency glaucoma.

Language: Английский

Citations

18
The concept of gene therapy for glaucoma DOI Creative Commons

Robert Sulak,

Xiaonan Liu, Adrian Smędowski

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(1), P. 92 - 99

Published: May 25, 2023

Gene therapies, despite of being a relatively new therapeutic approach, have potential to become an important alternative current treatment strategies in glaucoma. Since glaucoma is not considered single gene disease, the identified goals therapy would be rather provide neuroprotection retinal ganglion cells, especially, intraocular-pressure-independent manner. The most commonly reported type vector for delivery studies adeno-associated virus serotype 2 that has high tropism resulting long-term expression and low immunogenic profile. recruit inducible genetic animal models optic neuropathy, like DBA/2J mice model high-tension nerve crush-model. Reported therapy-based cells targeting specific genes translating growth factors (i.e., brain derived neurotrophic factor, its receptor TrkB), regulation apoptosis neurodegeneration Bcl-xl, Xiap, FAS system, nicotinamide mononucleotide adenylyl transferase 2, Digit3 Sarm1), immunomodulation Crry, C3 complement), modulation neuroinflammation erythropoietin), reduction excitotoxicity CamKIIα) transcription Max, Nrf2). On other hand, some focus on lowering intraocular pressure, by impacting involved both, decreasing aqueous humor production aquaporin 1), increasing outflow facility COX2, prostaglandin F2α receptor, RhoA/RhoA kinase signaling pathway, MMP1, Myocilin). goal this review summarize state-of-art direction development glaucomatous neuropathy.

Language: Английский

Citations

17
Retinal Ganglion Cell Transplantation: Approaches for Overcoming Challenges to Functional Integration DOI Creative Commons
Kevin Y. Zhang,

Erika A. Aguzzi,

Thomas V. Johnson

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1426 - 1426

Published: June 8, 2021

As part of the central nervous system, mammalian retinal ganglion cells (RGCs) lack significant regenerative capacity. Glaucoma causes progressive and irreversible vision loss by damaging RGCs their axons, which compose optic nerve. To functionally restore vision, lost must be replaced. Despite tremendous advancements in experimental models neuropathy that have elucidated pathways to induce endogenous RGC neuroprotection axon regeneration, obstacles achieving functional visual recovery through exogenous transplantation remain. Key challenges include poor graft survival, low donor neuron localization host retina, inadequate dendritogenesis synaptogenesis with afferent amacrine bipolar cells. In this review, we summarize current state transplantation, propose a set standard approaches quantifying reporting outcomes order guide collective effort advance field toward replacement nerve regeneration.

Language: Английский

Citations

35
Ciliary neurotrophic factor-mediated neuroprotection involves enhanced glycolysis and anabolism in degenerating mouse retinas DOI Creative Commons
Kun Do Rhee, Yanjie Wang, Johanna ten Hoeve

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 17, 2022

Abstract Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective cytokine in multiple models of retinal degeneration. To understand mechanisms underlying its broad effects, we have investigated the influence CNTF on metabolism mouse model photoreceptor treatment improves morphology mitochondria, but also leads to reduced oxygen consumption and suppressed respiratory chain activities. Molecular analyses show elevated glycolytic pathway gene transcripts active enzymes. Metabolomics detect significantly higher levels ATP energy currency phosphocreatine, metabolites, increased TCA cycle lipid biosynthetic intermediates, nucleotides, amino acids. Moreover, restores key antioxidant glutathione wild type level. Therefore, impacts metabolic status degenerating retinas by promoting aerobic glycolysis augmenting anabolic These findings reveal cellular enhanced neuronal viability suggest potential therapies for treating

Language: Английский

Citations

26
Neuroprotection in neurodegenerations of the brain and eye: Lessons from the past and directions for the future DOI Creative Commons
Leonard A. Levin, Christopher Patrick,

Nozhat Choudry

et al.

Frontiers in Neurology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 12, 2022

Neurological and ophthalmological neurodegenerative diseases in large part share underlying biology pathophysiology. Despite extensive preclinical research on neuroprotection that many cases bridges unifies both fields, only a handful of neuroprotective therapies have succeeded clinically either.

Language: Английский

Citations

25