Brimonidine Enhances the Electrophysiological Response of Retinal Ganglion Cells through the Trk-MAPK/ERK and PI3K Pathways in Axotomized Eyes

Yukita, Masayoshi; Omodaka, Kazuko; Machida, Shigeki; Yasuda, Masayuki; Sato, Kota; Maruyama, Kouichi; Nishiguchi, Koji M.; Nakazawa, Toru

doi:10.3109/02713683.2016.1153112

Cited by 8 publications

(8 citation statements)

References 29 publications

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“…3d). Similar results were reported by Ortín-Martínez et al, 22 where topical brimonidine had a protective effect on the cones, and by Yukita et al, 63 who observed conservation of RGC function under photopic conditions but without effect on the a and b waves of the scotopic ERG. Intraocular injection of brimonidine has also been shown to preserve outer nuclear layer thickness as measured by OCT 65 and even to reduce geographic atrophy secondary to age-related macular degeneration in a phase 2 study with a brimonidine drug delivery system.…”

Section: Papersupporting

confidence: 88%

“…The axonal protection provided by intravitreal brimonidine, associated with better anterograde and retrograde transport, has also been demonstrated by other groups. 63,64 The Bri-Lap intravitreal formulation also has a protective structural and functional effect on the retina in the early stages of treatment (up to week 8; p < 0.05). This was maintained in photoreceptors under photopic stimulation (but not under scotopic stimulation) in the later stages (week 24) (see Fig.…”

Section: Papermentioning

confidence: 96%

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Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model

et al. 2020

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Section: Papersupporting

confidence: 88%

Section: Papermentioning

confidence: 96%

Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model

et al. 2020

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“…Experimental studies have shown that brimonidine has also neuroprotective activity. In a rat model of axotomized eyes, intravitreal injection of brimonidine enhanced the survival and the electrophysiological activity of RGC, by activating the Trk-MAPK/ERK and Trk-PI3K signaling pathways [84]. Similarly, in a rat model of secondary neurodegeneration induced by partial crush of the optic nerve (thus independent of IOP elevation), the intraperitoneal administration of α 2r agonists (brimonidine, clonidine, and a synthetic compound AGN 191103) has been shown to be neuroprotective, whereas timolol injection had no effect [85].…”

Section: Brimonidinementioning

confidence: 99%

Neuroprotection in Glaucoma: Old and New Promising Treatments

Rusciano¹,

Pezzino²,

Mutolo

et al. 2017

Advances in Pharmacological Sciences

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Glaucoma is a major global cause of blindness, but the molecular mechanisms responsible for the neurodegenerative damage are not clear. Undoubtedly, the high intraocular pressure (IOP) and the secondary ischemic and mechanical damage of the optic nerve have a crucial role in retinal ganglion cell (RGC) death. Several studies specifically analyzed the events that lead to nerve fiber layer thinning, showing the importance of both intra-and extracellular factors. In parallel, many neuroprotective substances have been tested for their efficacy and safety in hindering the negative effects that lead to RGC death. New formulations of these compounds, also suitable for chronic oral administration, are likely to be used in clinical practice in the future along with conventional therapies, in order to control the progression of the visual impairment due to primary open-angle glaucoma (POAG). This review illustrates some of these old and new promising agents for the adjuvant treatment of POAG, with particular emphasis on forskolin and melatonin.

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“…Recently, it has been demonstrated ( Ortin-Martinez et al, 2014 ) that topical brimonidine protects retinal tissue in a light-emitting diode-induced phototoxicity. More recently, Yukita et al (2017) showed that brimonidine enhances the electrophysiological response of RGCs through the Trk-MAPK/ERK and PI3K pathways in axotomized rat eye, hypothesizing that these pathways regulate BDNF. Beside these important proofs, another inflammatory marker, called TRAIL, has been recently highlighted.…”

Section: Discussionmentioning

confidence: 99%

Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage

et al. 2021

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To investigate the neuroprotective effect of brimonidine after retinal ischemia damage on mouse eye. Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss, and high intraocular pressure. Ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mouse eyes were treated topically with brimonidine and pattern electroretinogram were used to assess the retinal ganglion cells (RGCs) function. A wide range of inflammatory markers, as well as anti-inflammatory and neurotrophic molecules, were investigated to figure out the potential protective effects of brimonidine in mouse retina. In particular, brain-derived neurotrophic factor (BDNF), IL-6, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor DR-5, TNF-α, GFAP, Iba-1, NOS, IL-1β and IL-10 were assessed in mouse retina that underwent to I/R insult with or without brimonidine treatment. Brimonidine provided remarkable RGCs protection in our paradigm. PERG amplitude values were significantly (p < 0.05) higher in brimonidine-treated eyes in comparison to I/R retinas. Retinal BDNF mRNA levels in the I/R group dropped significantly (p < 0.05) compared to the control group (normal mice); brimonidine treatment counteracted the downregulation of retinal BDNF mRNA in I/R eyes. Retinal inflammatory markers increased significantly (p < 0.05) in the I/R group and brimonidine treatment was able to revert that. The anti-inflammatory IL-10 decreased significantly (p < 0.05) after retinal I/R insult and increased significantly (p < 0.05) in the group treated with brimonidine. In conclusion, brimonidine was effective in preventing loss of function of RGCs and in regulating inflammatory biomarkers elicited by retinal I/R injury.

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Brimonidine Enhances the Electrophysiological Response of Retinal Ganglion Cells through the Trk-MAPK/ERK and PI3K Pathways in Axotomized Eyes

Abstract: Intravitreal brimonidine enhanced the survival and electrophysiological activity of the RGCs in rats. The mechanism of this electrophysiological change may involve activation of the Trk-MAPK/ERK and Trk-PI3K signals.

Cited by 8 publications

References 29 publications

Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model

Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model

Neuroprotection in Glaucoma: Old and New Promising Treatments

Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage

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