Intravitreal macrophage activation enables cat retinal ganglion cells to regenerate injured axons into the mature optic nerve

Okada, Takeshi; Ichikawa, Masahiro; Tokita, Yoshihito; Horie, Hidenori; Saito, Kiyoshi; Yoshida, Jun; Watanabe, Masami

doi:10.1016/j.expneurol.2005.07.015

Cited by 28 publications

(21 citation statements)

References 61 publications

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“…Intravitreal injection of two macrophage activators, oxidized galectin-1 and zymosan, strongly enhanced the regeneration of transected RGC axons beyond the ON crush site in adult cats. 44 …”

Section: Immune System and Neuroprotectionmentioning

confidence: 99%

Traumatic Optic Neuropathy Therapy: An Update of Clinical and Experimental Studies

Zhao

Wang

2008

J Int Med Res

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Section: Immune System and Neuroprotectionmentioning

confidence: 99%

Traumatic Optic Neuropathy Therapy: An Update of Clinical and Experimental Studies

Zhao

Wang

2008

J Int Med Res

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“…Apoptotic cell death was indicated because there was no difference in PI (propidium iodide) staining, yet TUNEL-positive cells were observed in the Vehicle rats. As for β-1,3-glucan, the results suggested a role in preventing apoptosis.Electroretinogram (ERGs) analysis of neuroprotective Treatments effect relative to Vehicle group: *p < 0.05. as confirmed by increased GFAP (Glial fibrillary acidic protein) expression, and subsequently releases CNTF followed by axonal regeneration of RGC (Leon et al, 2000, Okada et al, 2005. We surmised that β-1,3-glucan, the main component of zymosan, contributes to the release of CNTF.…”

mentioning

confidence: 96%

“…After the optic nerve is subjected to increased pressure, intravitreal injection of zymosan causes the axis plan reproduction of the pressure by inflow of macrophages, astrocytes and Müller cells (Hauk et al, 2008, Lorber et al, 2005, Muller et al, 2009, Okada et al, 2005. The astrocytes and Müller cells are directly involved in axonal regeneration; however, the role of macrophages in this regenerative process is still unclear (Hauk et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

^|^beta;-1,3-Glucan Attenuates Neuronal Cell Death after Transient Retinal Ischemia and Reperfusion

Nishio

Kumita

Uji

et al. 2013

FSTR

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The neuroprotective effect of intravitreally injected β-1,3-glucan was examined in a rat model of transient retinal ischemia. Retinal function and morphology were assessed in both control rats (Intact), and in rats administered β-1,3-glucan after ischemic damage induced by elevation of intraocular pressure (IOP) to 130 mmHg for 45 min. β-1,3-Glucan was intravitreally injected into male SD rats, with a final vitreal concentration of 5 µg/eye. Retinal function was assessed by electroretinography, and retinal morphology was assessed by light microscopy and TUNEL assay (n = 3 for Intact, and n = 6 for β-1,3-glucan and Vehicle). Morphometric analysis of retinal ganglion cells (RGCs) and the inner plexiform layer (IPL) showed decreased RGC number and thinner IPL in the eyes of Intact rats compared with those injected with β-1,3-glucan. TUNEL assay results showed that the retinas of eyes injected with β-1,3-glucan were similar to those of Intact eyes (the left eyes of the SD rats). However, the retinas of Vehicle eyes differed in RGC and IPL layer from β-1,3-glucan injected eyes after transient retinal ischemia. Electroretinograms (ERGs) showed that the β-1,3-glucan-administered rats had significantly more protective b-wave amplitudes compared with the Vehicle group. β-1,3-Glucan exhibits a neuroprotective effect in a transient retinal ischemia model of retinal injury in rats.Keywords: apoptosis, electroretinograms, intraocular pressure, retinal ischemia/reperfusion, β-1,3-glucan *To whom correspondence should be addressed. E-mail: umekawa@bio.mie-u.ac.jp † Present address: Present address: Institute of Clinical Research, National Hospital Organization, Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, Tokyo 152-8902, Japan IntroductionGlaucoma is one of the leading causes of vision loss in which the optic nerve is damaged. The disease is characterized by an increase in intraocular pressure (IOP), damaging the optic nerve and leading to subsequent loss of retinal ganglion cells and eventual loss of vision. Because the damage caused by high intraocular pressure is irreversible, next-generation glaucoma treatments will likely include retinal neuroprotective agents. The blood reperfusion increase in IOP is used as a model of closed-angle glaucoma. It is reported that apoptosis and sinking of the retinal ganglion cells (RGCs) appear systematically in this model, and this model can be used to examine characteristic pathological features, such as sinking optic papilla and apoptosis of RGCs (Grozdanic et al., 2003, Guo et al., 2005.Zymosan is extracted from bread yeast. After the optic nerve is subjected to increased pressure, intravitreal injection of zymosan causes the axis plan reproduction of the pressure by inflow of macrophages, astrocytes and Müller cells (Hauk et al., 2008, Lorber et al., 2005, Muller et al., 2009, Okada et al., 2005. The astrocytes and Müller cells are directly involved in axonal regeneration; however, the role of macrophages in this regenerative process is still unclear (Hauk et al., 2008). Zymosan ...

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“…They are taken up by RGCs and actively transported throughout the regenerating axons, which can thus be visualized after longitudinal sectioning of the optic nerve. The most commonly used tracers for anterograde transport are horse radish peroxidase (HRP), rhodamine isothiocyanate (RITC) and fluorescently labeled Cholera toxin subunit b (CTB) Vidal-Sanz et al 1987;Angelucci et al 1996;Leon et al 2000;Sapieha et al 2003;Okada et al 2005;de Lima et al 2012) (Fig. 3a).…”

Section: Imaging Modalities To Evaluate Optic Nerve Regenerationmentioning

confidence: 99%

Complementary research models and methods to study axonal regeneration in the vertebrate retinofugal system

et al. 2017

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Due to the lack of axonal regeneration, age-related deterioration in the central nervous system (CNS) poses a significant burden on the wellbeing of a growing number of elderly. To overcome this regenerative failure and to improve the patient's life quality, the search for novel regenerative treatment strategies requires valuable (animal) models and techniques. As an extension of the CNS, the retinofugal system, consisting of retinal ganglion cells that send their axons along the optic nerve to the visual brain areas, has importantly contributed to the current knowledge on mechanisms underlying the restricted regenerative capacities and to the development of novel strategies to enhance axonal regeneration. It provides an extensively used research tool, not only in amniote vertebrates including rodents, but also in anamniote vertebrates, such as zebrafish. Indeed, the latter show robust regeneration capacities, thereby providing insights into the factors that contribute to axonal regrowth and proper guidance, complementing studies in mammals. This review provides an integrative and critical overview of the classical and state-of-the-art models and methods that have been employed in the retinofugal system to advance our knowledge on the signaling pathways underlying the restricted versus robust axonal regeneration in rodents and zebrafish, respectively. In vitro, ex vivo and in vivo models and techniques to improve the visualization and analysis of regenerating axons are summarized. As such, the retinofugal system is presented as a valuable model to further facilitate research on axonal regeneration and to open novel therapeutic avenues for CNS pathologies.

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Intravitreal macrophage activation enables cat retinal ganglion cells to regenerate injured axons into the mature optic nerve

Cited by 28 publications

References 61 publications

Traumatic Optic Neuropathy Therapy: An Update of Clinical and Experimental Studies

Traumatic Optic Neuropathy Therapy: An Update of Clinical and Experimental Studies

^|^beta;-1,3-Glucan Attenuates Neuronal Cell Death after Transient Retinal Ischemia and Reperfusion

Complementary research models and methods to study axonal regeneration in the vertebrate retinofugal system

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