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Proceedings of the National Academy of... Nov 2022Axon regeneration is an energy-demanding process that requires active mitochondrial transport. In contrast to the central nervous system (CNS), axonal mitochondrial...
Axon regeneration is an energy-demanding process that requires active mitochondrial transport. In contrast to the central nervous system (CNS), axonal mitochondrial transport in regenerating axons of the peripheral nervous system (PNS) increases within hours and sustains for weeks after injury. Yet, little is known about targeting mitochondria in nervous system repair. Here, we report the induction of sustained axon regeneration, neural activities in the superior colliculus (SC), and visual function recovery after optic nerve crush (ONC) by M1, a small molecule that promotes mitochondrial fusion and transport. We demonstrated that M1 enhanced mitochondrial dynamics in cultured neurons and accelerated in vivo axon regeneration in the PNS. Ex vivo time-lapse imaging and kymograph analysis showed that M1 greatly increased mitochondrial length, axonal mitochondrial motility, and transport velocity in peripheral axons of the sciatic nerves. Following ONC, M1 increased the number of axons regenerating through the optic chiasm into multiple subcortical areas and promoted the recovery of local field potentials in the SC after optogenetic stimulation of retinal ganglion cells, resulting in complete recovery of the pupillary light reflex, and restoration of the response to looming visual stimuli was detected. M1 increased the gene expression of mitochondrial fusion proteins and major axonal transport machinery in both the PNS and CNS neurons without inducing inflammatory responses. The knockdown of two key mitochondrial genes, or , abolished the growth-promoting effects of M1 after ONC, suggesting that maintaining a highly dynamic mitochondrial population in axons is required for successful CNS axon regeneration.
Topics: Humans; Axons; Mitochondrial Proteins; Nerve Crush; Nerve Regeneration; Optic Nerve; Optic Nerve Injuries; Retinal Ganglion Cells; Sciatic Nerve; Small Molecule Libraries
PubMed: 36306327
DOI: 10.1073/pnas.2121273119 -
Biomedical Papers of the Medical... Sep 2023A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden...
PURPOSE
A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden decline in visual function. Despite the known complications of ethambutol treatment, it was discontinued after another three months.
METHODS
In the case report, we highlight the damage to the dominantly peripheral visual pathways. Using electrophysiological examinations, we showed a significant alteration in the optic nerves. Optical Coherence Tomography (OCT) showed progressive loss of vessel density and nerve fibre layer of retinal ganglion cells. Perimetric examination showed both a central decrease in sensitivity and mainly scotomas in the temporal parts of the visual fields. Although there was improvement in visual fields over time, OCT findings indicated progression of ethambutol-induced optic neuropathy (EON). Magnetic Resonance Imaging confirmed the alteration in the peripheral part of the visual pathway (intraorbital, intracranial parts of optic nerves, chiasma, and optic tracts).
CONCLUSION
Even though EON is not an unknown complication, new cases still occur and, unfortunately, with an irreversible course. Therefore, it is important to draw attention constantly to this complication and to consider it not only in ophthalmologists' surgeries.
Topics: Humans; Adult; Ethambutol; Antitubercular Agents; Optic Nerve Diseases; Optic Nerve; Tuberculosis; Tomography, Optical Coherence
PubMed: 35582729
DOI: 10.5507/bp.2022.022 -
International Journal of Molecular... Jul 2019Retinal ganglion cells (RGCs) extend axons out of the retina to transmit visual information to the brain. These connections are established during development through... (Review)
Review
Retinal ganglion cells (RGCs) extend axons out of the retina to transmit visual information to the brain. These connections are established during development through the navigation of RGC axons along a relatively long, stereotypical pathway. RGC axons exit the eye at the optic disc and extend along the optic nerves to the ventral midline of the brain, where the two nerves meet to form the optic chiasm. In animals with binocular vision, the axons face a choice at the optic chiasm-to cross the midline and project to targets on the contralateral side of the brain, or avoid crossing the midline and project to ipsilateral brain targets. Ipsilaterally and contralaterally projecting RGCs originate in disparate regions of the retina that relate to the extent of binocular overlap in the visual field. In humans virtually all RGC axons originating in temporal retina project ipsilaterally, whereas in mice, ipsilaterally projecting RGCs are confined to the peripheral ventrotemporal retina. This review will discuss recent advances in our understanding of the mechanisms regulating specification of ipsilateral versus contralateral RGCs, and the differential guidance of their axons at the optic chiasm. Recent insights into the establishment of congruent topographic maps in both brain hemispheres also will be discussed.
Topics: Animals; Axons; Brain; Cell Lineage; Humans; Retinal Ganglion Cells; Vision, Binocular; Visual Pathways
PubMed: 31277365
DOI: 10.3390/ijms20133282 -
Frontiers in Aging Neuroscience 2021The death of retinal ganglion cells (RGCs) is a key factor in the pathophysiology of all types of glaucoma, but the mechanism of pathogenesis of glaucoma remains... (Review)
Review
The death of retinal ganglion cells (RGCs) is a key factor in the pathophysiology of all types of glaucoma, but the mechanism of pathogenesis of glaucoma remains unclear. RGCs are a group of central nervous system (CNS) neurons whose soma are in the inner retina. The axons of RGCs form the optic nerve and converge at the optic chiasma; from there, they project to the visual cortex the lateral geniculate nucleus (LGN). In recent years, there has been increasing interest in the dysfunction and death of CNS and retinal neurons caused by transneuronal degeneration of RGCs, and the view that glaucoma is a widespread neurodegenerative disease involving CNS damage appears more and more frequently in the literature. In this review, we summarize the current knowledge of LGN and visual cortex neuron damage in glaucoma and possible mechanisms behind the damage. This review presents an updated and expanded view of neuronal damage in glaucoma, and reveals new and potential targets for neuroprotection and treatment.
PubMed: 33889083
DOI: 10.3389/fnagi.2021.643685 -
Ophthalmology Feb 2021The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular...
PURPOSE
The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular changes as typical features. The objective of this study was to investigate if microgravity can create deformations or movements of the eye or optic nerve, and if such changes could be linked to SANS.
DESIGN
Cohort study.
PARTICIPANTS
Twenty-two astronauts (age 48 ± 4 years).
METHODS
The intervention consisted of time in microgravity at the ISS. We co-registered pre- and postspaceflight magnetic resonance imaging (MRI) scans and generated centerline representations of the optic nerve. The coordinates for the optic nerve head (ONH) and optic chiasm (OC) ends of the optic nerve were recorded along with the entire centerline path.
MAIN OUTCOME MEASURES
Optic nerve length, ONH movement, and OC movement after time in microgravity.
RESULTS
Optic nerve length increased (0.80 ± 0.74 mm, P < 0.001), primarily reflecting forward ONH displacement (0.63 ± 0.53 mm, P < 0.001). The forward displacement was positively related to mission duration, preflight body weight, and clinical manifestations of SANS. We also detected upward displacement of the OC (0.39 ± 0.50 mm, P = 0.002), indicative of brain movement, but this observation could not be linked to SANS.
CONCLUSIONS
The spaceflight-induced optic nerve lengthening and anterior movement of the ONH support that SANS is caused by an altered pressure difference between the brain and the eye, leading to a forward push on the posterior of the eye. Body weight is a potential contributing risk factor. Direct assessment of intracranial pressure in space is required to verify the implicated mechanism behind the ocular findings in SANS.
Topics: Astronauts; Cohort Studies; Extraterrestrial Environment; Female; Humans; Intracranial Pressure; Magnetic Resonance Imaging; Male; Middle Aged; Optic Disk; Optic Nerve; Papilledema; Space Flight; Syndrome; Time Factors; Vision Disorders; Weightlessness
PubMed: 32659310
DOI: 10.1016/j.ophtha.2020.07.007 -
Frontiers in Oncology 2023Diencephalic tumors tend to be low grade tumors located near several critical structures, including the optic nerves, optic chiasm, pituitary, hypothalamus, Circle of... (Review)
Review
Diencephalic tumors tend to be low grade tumors located near several critical structures, including the optic nerves, optic chiasm, pituitary, hypothalamus, Circle of Willis, and hippocampi. In children, damage to these structures can impact physical and cognitive development over time. Thus, the goal of radiotherapy is to maximize long term survival while minimizing late effects, including endocrine disruption leading to precocious puberty, height loss, hypogonadotropic hypogonadism, and primary amenorrhea; visual disruption including blindness; and vascular damage resulting in cerebral vasculopathy. Compared to photon therapy, proton therapy offers the potential to decrease unnecessary dose to these critical structures while maintaining adequate dose to the tumor. In this article, we review the acute and chronic toxicities associated with radiation for pediatric diencephalic tumors, focusing on the use of proton therapy to minimize treatment-related morbidity. Emerging strategies to further reduce radiation dose to critical structures will also be considered.
PubMed: 37213290
DOI: 10.3389/fonc.2023.1123082