Mechanisms of secondary degeneration after partial optic nerve transection

Li, Hong Ying; Ruan, Yiwen; Ren, Chaoran; Cui, Qing; So, Kwok-Fai

doi:10.4103/1673-5374.130093

Cited by 59 publications

(31 citation statements)

References 86 publications

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“…Visual impairment resulting from glaucoma is caused by the primary degeneration of RGCs and secondary degeneration affecting cell types up- and downstream in the visual signaling pathway, such as other retinal or CNS neurons (Li et al, 2014; Melamed, 2002; Yoles et al, 1999). Therefore, the most common tests for the assessment the effects of glaucomatous optic neuropathy on visual performance are visual water task (two-way forced choice swimming test) and OMR tests, as they are highly reliant on the appropriate response of functioning RGCs and involve the whole or most components of the visual pathway.…”

Section: Behavioral Assays Measuring Deficits In Rodent Visual Promentioning

confidence: 99%

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Grillo

Koulen

2015

Experimental Eye Research

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Processing of visual information begins in the retina, with photoreceptors converting light stimuli into neural signals. Ultimately, signals are transmitted to the brain through signaling networks formed by interneurons, namely bipolar, horizontal and amacrine cells providing input to retinal ganglion cells (RGCs), which form the optic nerve with their axons. As part of the chronic nature of glaucomatous optic neuropathy, the increasing and irreversible damage and ultimately loss of neurons, RGCs in particular, occurs following progressive damage to the optic nerve head (ONH), eventually resulting in visual impairment and visual field loss. There are two behavioral assays that are typically used to assess visual deficits in glaucoma rodent models, the visual water task and the optokinetic drum. The visual water task can assess an animal’s ability to distinguish grating patterns that are associated with an escape from water. The optokinetic drum relies on the optomotor response, a reflex turning of the head and neck in the direction of the visual stimuli, which usually consists of rotating black and white gratings. This reflex is a physiological response critical for keeping the image stable on the retina. Driven initially by the neuronal input from direction-selective RGCs, this reflex is comprised of a number of critical sensory and motor elements. In the presence of repeatable and defined stimuli, this reflex is extremely well suited to analyze subtle changes in the circuitry and performance of retinal neurons. Increasing the cycles of these alternating gratings per degree, or gradually reducing the contrast of the visual stimuli, threshold levels can be determined at which the animal is no longer tracking the stimuli, and thereby visual function of the animal can be determined non-invasively. Integrating these assays into an array of outcome measures that determine multiple aspects of visual function is a central goal in vision research and can be realized, for example, by the combination of measuring optomotor reflex function with electroretinograms (ERGs) and optical coherence tomography (OCT) of the retina. These structure-function correlations in vivo are urgently needed to identify disease mechanisms as potential new targets for drug development. Such a combination of the experimental assessment of the optokinetic reflex (OKN) or optomotor reflex (OMR) with other measures of retinal structure and function is especially valuable for research on GON. The chronic progression of the disease is characterized by a gradual decrease in function accompanied by a concomitant increase in structural damage to the retina, therefore the assessment of subtle changes is key to determining the success of novel intervention strategies.

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Section: Behavioral Assays Measuring Deficits In Rodent Visual Promentioning

confidence: 99%

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Grillo

Koulen

2015

Experimental Eye Research

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“…Second, retinal glial cells such as microglia, astrocytes, and oligodendrocytes also played a role in the secondary degeneration after pONC, 39,40 which may also contribute to the D change observed here; however, the specific mechanisms of these complex pathologies need further study. 41,42 …”

Section: Discussionmentioning

confidence: 99%

Optical Detection of Early Damage in Retinal Ganglion Cells in a Mouse Model of Partial Optic Nerve Crush Injury

Puyang

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeElastic light backscattering spectroscopy (ELBS) has exquisite sensitivity to the ultrastructural properties of tissue and thus has been applied to detect various diseases associated with ultrastructural alterations in their early stages. This study aims to test whether ELBS can detect early damage in retinal ganglion cells (RGCs).MethodsWe used a mouse model of partial optic nerve crush (pONC) to induce rapid RGC death. We confirmed RGC loss by axon counting and characterized the changes in retinal morphology by optical coherence tomography (OCT) and in retinal function by full-field electroretinogram (ERG), respectively. To quantify the ultrastructural properties, elastic backscattering spectroscopic analysis was implemented in the wavelength-dependent images recorded by reflectance confocal microscopy.ResultsAt 3 days post-pONC injury, no significant change was found in the thickness of the RGC layer or in the mean amplitude of the oscillatory potentials measured by OCT and ERG, respectively; however, we did observe a significantly decreased number of axons compared with the controls. At 3 days post-pONC, we used ELBS to calculate the ultrastructural marker (D), the shape factor quantifying the shape of the local mass density correlation functions. It was significantly reduced in the crushed eyes compared with the controls, indicating the ultrastructural fragmentation in the crushed eyes.ConclusionsElastic light backscattering spectroscopy detected ultrastructural neuronal damage in RGCs following the pONC injury when OCT and ERG tests appeared normal. Our study suggests a potential clinical method for detecting early neuronal damage prior to anatomical alterations in the nerve fiber and ganglion cell layers.

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“…The retinofugal system is a powerful model system to investigate the mechanisms underlying (restricted) regenerative capacity, to study the molecules that affect axonal regeneration and to develop new strategies to stimulate axonal regeneration in the adult mammalian CNS. 2,3 Indeed, (1) the optic nerve and retina are the most accessible regions of the CNS; (2) their morphology and function are well characterized; (3) the axons of the optic nerve originate from a single population of projection neurons, the retinal ganglion cells (RGCs); (4) the typical organization of the glial cells facilitates the study of glial reactivity; (5) RGCs can be manipulated with low-invasive techniques; and (6) the vitreous body can be used as a reservoir for the administration of drugs, molecules and recombinant genes. 3,4 The optic nerve crush and optic nerve transection paradigms are widely used in rodents to induce local axonal damage and investigate RGC survival and axonal regeneration 4 , as well as glial scar formation and inflammation.…”

Section: The Retinofugal System As a Model To Study Axonal Regenerationmentioning

confidence: 99%

Neuroinflammation and Optic Nerve Regeneration: Where Do We Stand in Elucidating Underlying Cellular and Molecular Players?

Andries

Groef

Moons

2019

Current Eye Research

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Neurodegenerative diseases and central nervous system (CNS) trauma are highly irreversible, in part because adult mammals lack a robust regenerative capacity. A multifactorial problem underlies the limited axonal regeneration potential. Strikingly, neuroinflammation seems able to induce axonal regrowth in the adult mammalian CNS. It is increasingly clear that both blood-borne and resident inflammatory cells as well as reactivated glial cells affect axonal regeneration. The scope of this review is to give a comprehensive overview of the knowledge that links inflammation (with a focus on the innate immune system) to axonal regeneration and to critically reflect on the controversy that still prevails about the cells, molecules and pathways that are dominating the scene. Also, a brief overview is given of what is already known about the crosstalk between and the heterogeneity of cell types that might play a role in axonal regeneration. Recent research indicates that inflammation-induced axonal regrowth is not solely driven by a single-cell population but probably relies on the crosstalk between multiple cell types and the strong regulation of these cell populations in time and space. Moreover, there is growing evidence that the different cell populations are highly heterogeneous and as such can react differently upon injury. This could explain the controversial results that have been obtained over the past years. The primary focus of this manuscript is the retinofugal system of adult mammals, however, when relevant, insights or examples of the spontaneous regenerating zebrafish model and spinal cord research are added.

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Mechanisms of secondary degeneration after partial optic nerve transection

Cited by 59 publications

References 86 publications

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Optical Detection of Early Damage in Retinal Ganglion Cells in a Mouse Model of Partial Optic Nerve Crush Injury

Neuroinflammation and Optic Nerve Regeneration: Where Do We Stand in Elucidating Underlying Cellular and Molecular Players?

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