Bilateral retinal microglial response to unilateral optic nerve transection in rats

Cen, Ling-Ping; Han, Moon Ku; Zhou, Lei; Tan, Liang; Liang, Ji‐Zhao; Pang, Chi Pui; Zhang, M.

doi:10.1016/j.neuroscience.2015.09.067

Cited by 27 publications

(25 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The IPL in the retina contralateral to the injured optic nerve showed a small, transient elevation of Zn 2+ ( Fig. S2 A-C), reminiscent of other contralateral effects reported after unilateral optic nerve injury (64). Because the contralateral signal changes over time, we used the normal, intact retina as a reference throughout the study, always staining control and experimental retinas together.…”

Section: Znmentioning

confidence: 81%

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration

Andereggen

Yuki

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

123

129

View full text Add to dashboard Cite

Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn 2+ ) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn 2+ increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn 2+ accumulation in amacrine cell processes involves the Zn 2+ transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn 2+ chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn 2+ chelation extends for several days after nerve injury. These results show that retinal Zn 2+ dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn 2+ chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.T he optic nerve has been widely used to investigate the response of CNS neurons to injury because of its accessibility, anatomy, and functional importance. Under normal circumstances, retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate axons after the optic nerve has been damaged and soon undergo cell death, leaving victims of traumatic or ischemic nerve injury or degenerative conditions, such as glaucoma, with permanent visual losses. Optic nerve injury leads to numerous pathological changes in RGCs and reversing some of these changes improves cell survival, although these effects are often transitory and for the most part promote little or no axon regeneration (1-10). Regeneration per se can be induced by intraocular inflammation combined with elevated cAMP (11, 12), counteracting cell-intrinsic (13-15) or cellextrinsic (16, 17) suppressors of axon growth, oncomodulin and other growth factors (18-22), or elevated physiological activity (23,24). Some of these treatments act synergistically and enable a modest number of RGCs to reestablish connections with appropriate target areas in the brain (25-27). However, although these studies show that successful regeneration can occur in principle, most RGCs eventually die after optic nerve injury, and to date only a small fraction of surviving RGCs have been induced to regenerate axons (27). These observations imply the existence of other major, as yet unknown suppressors of cell survival and regeneration. Our results point to zinc dysregulation as a critical factor.Zinc is essential for many cellular functions. Covalently bound zinc is required for the activity of numerous enzymes and t...

show abstract

Section: Znmentioning

confidence: 81%

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration

Andereggen

Yuki

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

123

129

View full text Add to dashboard Cite

show abstract

“…Experimental unilateral transection of the optic nerve also causes acute glial activation of the retina on the contralateral side (1)(2)(3). These experiments suggest that the processes of bilateral glial activation actually may also occur on the level of the retinal ganglion cells in the visual tract in humans.…”

Section: Introductionmentioning

confidence: 78%

“…Structural magnetic resonance imaging was performed in the basic planes using the following sequences: T1 TFE SAG 3D 1x1x1 mm 3 , TR=8.1 ms, TE=3.7 ms, NSA 1, 170 slices; T2 mDIXON COR 2.5 mm, TR=3,000 ms, TE=80 ms, 36 slices; T2 4 mm TRA, TR=3,000 ms, TE=80 ms, NSA 1, 30 slices; FLAIR 4 mm, TR=11,000 ms, TE=125 ms; VenBold, TR=15 ms, TE=21 ms, NSA 2, 3DFFE 1x1x1 mm 3 , 290 slices; T1 IR COR 5 mm, TR=3873 ms, TE=15 ms, NSA 1, 28 slices, gap 1; and DWI 4 mm, TR=3,443 ms, TE=76 ms, b-factor 0-800, 30 slices. RNFL and GCC were examined using SD-OCT RTvue 100 with navigation on the right and fixation of a light point 37 and 50 months from the first ophthalmological testing on the left.…”

Section: Methodsmentioning

confidence: 99%

Traumatic optic neuropathy‑a contralateral finding: A case report

Kyncl¹,

Lešták²,

Tintěra³

et al. 2019

Exp Ther Med

View full text Add to dashboard Cite

The present study demonstrates alterations of the contralateral side optic tract to an optic nerve traumatic lesion. Visual acuity of the right eye following Traumatic optic neuropathy (TON) remained at 0 following the injury. Electrophysiological examination using pattern electroretinogram revealed values reduced by 50% in the right eye compared with the left eye. Pattern visual-evoked potential evaluation indicated a bilateral lesion with a higher decrease following right eye stimulation. Magnetic resonance imaging revealed right optic nerve atrophy. Functional magnetic resonance imaging indicated decreased activity of the visual centre during left eye stimulation. The present study revealed contralateral visual tract alterations following unilateral injury, and hypothesize that the ganglion cells of the retina respond initially to glial activation. These changes are, in our view, followed by changes in the visual pathway.

show abstract

“…94 In the case of an optic nerve injury, microglia density increases from 3 days after injury onwards and only returns to baseline numbers after 6 weeks. 97 This sustained increase coincides with the period during which RGC death occurs, and microglia actively phagocytize debris from these RGCs and their axons. 97,98 Notably, the increase in microglial cell number after optic nerve injury may not only originate from local proliferation but also from the infiltration of blood-derived macrophages.…”

Section: Resident Inflammatory Cellsmicrogliamentioning

confidence: 91%

“…97,98 Notably, the increase in microglial cell number after optic nerve injury may not only originate from local proliferation but also from the infiltration of blood-derived macrophages. 97 Since it has long been difficult to discriminate between resident microglia and infiltrating macrophages, 99 the relative contribution of these processes remains unclear.…”

Section: Resident Inflammatory Cellsmicrogliamentioning

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

View full text Add to dashboard Cite

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.

show abstract

Bilateral retinal microglial response to unilateral optic nerve transection in rats

Cited by 27 publications

References 31 publications

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration

Traumatic optic neuropathy‑a contralateral finding: A case report

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

Contact Info

Product

Resources

About