Glaucomatous optic neuropathy: Mitochondrial dynamics, dysfunction and protection in retinal ganglion cells

Progress in Retinal and Eye Research, Journal Year: 2022, Volume and Issue: 95, P. 101136 - 101136

Published: Nov. 16, 2022

Glaucoma is a leading cause of irreversible blindness worldwide and characterized by slow, progressive, multifactorial degeneration retinal ganglion cells (RGCs) their axons, resulting in vision loss. Despite its high prevalence individuals 60 years age older, the causing factors contributing to glaucoma progression are currently not well characterized. Intraocular pressure (IOP) only proven treatable risk factor. However, lowering IOP insufficient for preventing disease progression. One significant interests pathogenesis understanding structural functional impairment mitochondria RGCs axons synapses. Glaucomatous such as elevation, aging, genetic variation, neuroinflammation, neurotrophic factor deprivation, vascular dysregulation, potential inducers mitochondrial dysfunction glaucoma. Because oxidative phosphorylation stress-mediated associated with glaucomatous RGCs, underlying mechanisms relationship between alterations would be beneficial developing mitochondria-related neuroprotection synapses against neurodegeneration. Here, we review current studies focusing on dynamics-based therapeutic strategies protect

Language: Английский

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Spiking Neural Networks: A Survey

IEEE Access, Journal Year: 2022, Volume and Issue: 10, P. 60738 - 60764

Published: Jan. 1, 2022

The field of Deep Learning (DL) has seen a remarkable series developments with increasingly accurate and robust algorithms. However, the increase in performance been accompanied by an parameters, complexity, training inference time models, which means that we are rapidly reaching point where DL may no longer be feasible. On other hand, some specific applications need to carefully considered when developing models due hardware limitations or power requirements. In this context, there is growing interest efficient algorithms, Spiking Neural Networks (SNNs) being one most promising paradigms. Due inherent asynchrony sparseness spike trains, these types networks have potential reduce consumption while maintaining relatively good performance. This attractive for if successful, could replace traditional Artificial (ANNs) many applications. despite significant progress, SNNs on benchmark datasets often lower than ANNs. Moreover, non-differentiable nature their activation functions, it difficult train direct backpropagation, so appropriate strategies must found. Nevertheless, efforts made develop competitive models. survey covers main ideas behind reviews recent trends learning rules network architectures, particular focus biologically inspired strategies. It also provides practical considerations state-of-the-art discusses relevant research opportunities.

Language: Английский

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Early-stage visual perception impairment in schizophrenia, bottom-up and back again

Schizophrenia, Journal Year: 2022, Volume and Issue: 8(1)

Published: March 21, 2022

Abstract Visual perception is one of the basic tools for exploring world. However, in schizophrenia, this modality disrupted. So far, there has been no clear answer as to whether disruption occurs primarily within brain or precortical areas visual (the retina, pathways, and lateral geniculate nucleus [LGN]). A web-based comprehensive search peer-reviewed journals was conducted based on various keyword combinations including saliency, cognition, LGN. Articles were chosen with respect topic relevance. Searched databases included Google Scholar, PubMed, Web Science. This review describes circuit key changes biochemistry pathophysiology that affect creation characteristics retinal signal well its subsequent modulation processing other parts circuit. Changes misinterpretation stimuli associated them may, a result, contribute development schizophrenic disease.

Language: Английский

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Pan-retinal ganglion cell markers in mice, rats, and rhesus macaques

动物学研究, Journal Year: 2022, Volume and Issue: 44(0), P. 1 - 23

Published: Jan. 1, 2022

Univocal identification of retinal ganglion cells (RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent phenotypic markers, RGCs were normally identified using retrograde tracing retinorecipient areas. This invasive technique, its use precluded in higher mammals such as monkeys. In past decade, several RGC markers have been described. Here, we reviewed analyzed specificity nine used to identify all or most RGCs, i.e., pan-RGC rats, mice, macaques. The best three species terms specificity, proportion labeled, indicators viability BRN3A, expressed by vision-forming RBPMS, vision- non-vision-forming RGCs. NEUN, often was non-RGCs cell layer, therefore not RGC-specific. γ-SYN, TUJ1, NF-L labeled axons, which impaired detection somas central retina but would be good morphology. TUJ1 also non-RGCs. BM88, ERRβ, PGP9.5 are rarely they rats macaques ERRβ mice. However, BM88 suitable viability.

Language: Английский

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Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium

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

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Metformin protects against retinal ischemia/reperfusion injury through AMPK-mediated mitochondrial fusion

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 205, P. 47 - 61

Published: May 28, 2023

Retinal ischemia/reperfusion (I/R) injury is a common pathological process responsible for cellular damage in glaucoma, diabetic retinopathy and hypertensive retinopathy. Metformin biguanide drug that exerts strong effects on multiple diseases. This study aims to evaluate the protective effect of metformin against retinal I/R its underlying mechanism. induced reduction retina thickness cell number ganglion layer, alleviated I/R-induced injury. Both simulated (SIR) R28 cells down-regulated expression mitochondrial fusion protein Mfn2 OPA1, which led fission. also cells, reversed alteration fission membrane potential (MMP) disruption-induced by or SIR as well. Intriguingly, inhibition AMPK compound C siRNA prevented metformin-mediated up-regulation OPA1. Compound knockdown OPA1 dramatically intracellular ROS generation, MMP disruption, loss RGCs layer-induced I/R. Moreover, scavenging (mito-ROS) mito-TEMPO exerted similar protection SIR-induced metformin. Our data show first time protects through AMPK-mediated decreased mito-ROS generation. These findings might repurpose therapeutic agent

Language: Английский

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The Blue Light Hazard Versus Blue Light Hype

American Journal of Ophthalmology, Journal Year: 2022, Volume and Issue: 240, P. 51 - 57

Published: Feb. 25, 2022

Language: Английский

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Current Insights Into Oligodendrocyte Metabolism and Its Power to Sculpt the Myelin Landscape

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: April 28, 2022

Once believed to be part of the nervenkitt or “nerve glue” network in central nervous system (CNS), oligodendroglial cells now have established roles key neurological functions such as myelination, neuroprotection, and motor learning. More recently, oligodendroglia has become subject intense investigations aimed at understanding contributions its energetics CNS physiology pathology. In this review, we discuss current metabolism regulating stages development health, role providing energy neighboring neurons, well how alterations bioenergetics contribute disease states. Importantly, highlight certain inputs can regulate metabolism, including extrinsic intrinsic mediators cellular signaling, pharmacological compounds, even dietary interventions. Lastly, emerging studies discovering therapeutic potential targeting components within bioenergetic pathways.

Language: Английский

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Morpho-functional analysis of the early changes induced in retinal ganglion cells by the onset of diabetic retinopathy: The effects of a neuroprotective strategy

Pharmacological Research, Journal Year: 2022, Volume and Issue: 185, P. 106516 - 106516

Published: Oct. 19, 2022

Retinal ganglion cells (RGCs) are highly susceptible to diabetes-induced metabolic stress. This study describes the early responses of RGCs hyperglycemia and examines effects neuroprotective somatostatin analog octreotide (OCT). Thy1-green fluorescent protein (GFP)-M transgenic mice were used, which express GFP in a number RGCs. OCT was intravitreally injected with streptozotocin (STZ)-induced diabetes. A longitudinal electroretinography (ERG) analysis performed up 2 weeks from STZ treatment. RGC density measured extensive morphometric analyses on identified subtypes. treatment caused decline function, counteracted by OCT. No differences recorded, indicating that impaired activity unlikely be related death. Different GFP-labeled subtypes analyzed. Overall, large mostly affected diabetes responded treatment, while those smaller dendritic arborizations less involved. Interestingly, depending complexity tree, could completely rescue parameters or increase hyperglycemia. There is an response diabetes, involves specific morpho-functional deficits but not overt cell induces adaptive changes that, although different among subtypes, contribute functionality presence These results highlight importance neuronal protection phases diabetic retinopathy, when loss has yet started morphology can preserved adjusted maintain physiology.

Language: Английский

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Signal processing in the vagus nerve: Hypotheses based on new genetic and anatomical evidence

Biological Psychology, Journal Year: 2023, Volume and Issue: 182, P. 108626 - 108626

Published: July 6, 2023

Each organism must regulate its internal state in a metabolically efficient way as it interacts space and time with an ever-changing only partly predictable world. Success this endeavor is largely determined by the ongoing communication between brain body, vagus nerve crucial structure that dialogue. In review, we introduce novel hypothesis afferent engaged signal processing rather than just relay. New genetic structural evidence of vagal fiber anatomy motivates two hypotheses: (1) sensory signals informing on physiological body compute both spatial temporal viscerosensory features they ascend nerve, following patterns found other architectures, such visual olfactory systems; (2) ascending descending modulate one another, calling into question strict segregation motor signals, respectively. Finally, discuss several implications our hypotheses for understanding role predictive energy regulation (i.e., allostasis) well metabolic memory disorders prediction (e.g., mood disorders).

Language: Английский

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