Elevation of Intraocular Glutamate Levels in Rats With Partial Lesion of the Optic Nerve

Abstract

Background: Acute partial lesion of the rat optic nerve, although not a model for glaucoma, mimics some of the features of the disease. Objective: To learn whether degeneration of rat optic nerve fibers and death of their retinal ganglion cells induced by an acute partial lesion are associated with elevated levels of glutamate, known to occur in the eyes of humans and monkeys with glaucoma. Materials and Methods: Rat optic nerve was subjected to a partial crush injury. Aqueous humor samples were aspirated from the anterior and posterior aqueous chambers at specified times and their amino acid contents were determined by means of high-performance liquid chromatography. Results: Three and 7 days after injury, intraocular glutamate and aspartate levels were found to be significantly higher than in normal or sham-operated-on eyes, and returned to normal by day 14.

Upregulation ofEphB2andephrin-B2at the Optic Nerve Head of DBA/2J Glaucomatous Mice Coincides with Axon Loss

“…This idea has led to the use of acute optic nerve injury as a model for glaucoma. 53,54 Results from the present study showed that both optic nerve trauma and glaucoma indeed triggered the upregulation of EphB proteins in macrophages at the site of injury. Given that EphB and ephrin-B proteins have also been implicated in regulating axon responses in spinal cord injury, 26 -28,55 this protein family may play a key role in various types of axon damage throughout the nervous system.…”

Upregulation ofEphB2andephrin-B2at the Optic Nerve Head of DBA/2J Glaucomatous Mice Coincides with Axon Loss

“…This idea has led to the use of acute optic nerve injury as a model for glaucoma. 53,54 Results from the present study showed that both optic nerve trauma and glaucoma indeed triggered the upregulation of EphB proteins in macrophages at the site of injury. Given that EphB and ephrin-B proteins have also been implicated in regulating axon responses in spinal cord injury, 26 -28,55 this protein family may play a key role in various types of axon damage throughout the nervous system.…”

Neuroprotection of retinal ganglion cells by agonism of the beta but not the alpha oestrogen receptor in the axotomized retina of male and female mice

“…ERα has been shown to activate the same pathways as mGlu1 receptors (Spampinato et al, 2012), which are implicated in excitotoxic RGC degeneration (Liberatore et al, 2017). This aligns with the multifactorial nature of axotomyinduced RGC death, which activates multiple cell death pathways (Agudo et al, 2009) and includes excitotoxicity driven by axotomy-induced glutamate release (Vorwerk et al, 2004;Yoles & Schwartz, 1998;Yoles et al, 1997).…”

Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages

“…To understand the involvement of myeloid immune cells (resident and infiltrating) in the dynamic events occurring after retinal insult, we first studied this population in the adult retina under physiological and pathological conditions. We chose to use a model of retinal intoxication with glutamate (Schori et al, 2002; Schwartz and Kipnis, 2007), a common mediator of toxicity under neurodegenerative conditions (Dreyer et al, 1996; Shaw and Ince, 1997; Yoles and Schwartz, 1998; Dirnagl et al, 1999; Vorwerk et al, 1999; Gupta and Yücel, 2007). Surviving RGCs were assessed in this study 7 d after glutamate intoxication by immunostaining for Brn3a, a specific RGC marker (Nadal-Nicolás et al, 2009; Fig.…”

“…Our results suggest that coping with retinal injury requires a regulated immune response in which monocyte-derived macrophages are essential and intimate partners. Because the main experimental model of this study was glutamate intoxication, a phenomenon relevant to many CNS neurodegenerative disorders (Dreyer et al, 1996; Shaw and Ince, 1997; Yoles and Schwartz, 1998; Dirnagl et al, 1999; Vorwerk et al, 1999), our findings have far-reaching implications that extend beyond the eye. The outcomes of this study suggest the possible therapeutic potential of these cells as unique endogenous neuroprotective agents in treating retinal neuropathies as well as other CNS pathologies that involve neuronal loss.…”

Upregulation ofEphB2andephrin-B2at the Optic Nerve Head of DBA/2J Glaucomatous Mice Coincides with Axon Loss

“…This idea has led to the use of acute optic nerve injury as a model for glaucoma. 53,54 Results from the present study showed that both optic nerve trauma and glaucoma indeed triggered the upregulation of EphB proteins in macrophages at the site of injury. Given that EphB and ephrin-B proteins have also been implicated in regulating axon responses in spinal cord injury, 26 -28,55 this protein family may play a key role in various types of axon damage throughout the nervous system.…”

Neuroprotection of retinal ganglion cells by agonism of the beta but not the alpha oestrogen receptor in the axotomized retina of male and female mice

“…ERα has been shown to activate the same pathways as mGlu1 receptors (Spampinato et al, 2012), which are implicated in excitotoxic RGC degeneration (Liberatore et al, 2017). This aligns with the multifactorial nature of axotomyinduced RGC death, which activates multiple cell death pathways (Agudo et al, 2009) and includes excitotoxicity driven by axotomy-induced glutamate release (Vorwerk et al, 2004;Yoles & Schwartz, 1998;Yoles et al, 1997).…”

Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages

“…To understand the involvement of myeloid immune cells (resident and infiltrating) in the dynamic events occurring after retinal insult, we first studied this population in the adult retina under physiological and pathological conditions. We chose to use a model of retinal intoxication with glutamate (Schori et al, 2002; Schwartz and Kipnis, 2007), a common mediator of toxicity under neurodegenerative conditions (Dreyer et al, 1996; Shaw and Ince, 1997; Yoles and Schwartz, 1998; Dirnagl et al, 1999; Vorwerk et al, 1999; Gupta and Yücel, 2007). Surviving RGCs were assessed in this study 7 d after glutamate intoxication by immunostaining for Brn3a, a specific RGC marker (Nadal-Nicolás et al, 2009; Fig.…”

“…Our results suggest that coping with retinal injury requires a regulated immune response in which monocyte-derived macrophages are essential and intimate partners. Because the main experimental model of this study was glutamate intoxication, a phenomenon relevant to many CNS neurodegenerative disorders (Dreyer et al, 1996; Shaw and Ince, 1997; Yoles and Schwartz, 1998; Dirnagl et al, 1999; Vorwerk et al, 1999), our findings have far-reaching implications that extend beyond the eye. The outcomes of this study suggest the possible therapeutic potential of these cells as unique endogenous neuroprotective agents in treating retinal neuropathies as well as other CNS pathologies that involve neuronal loss.…”

Upregulation ofEphB2andephrin-B2at the Optic Nerve Head of DBA/2J Glaucomatous Mice Coincides with Axon Loss

“…This idea has led to the use of acute optic nerve injury as a model for glaucoma. 53,54 Results from the present study showed that both optic nerve trauma and glaucoma indeed triggered the upregulation of EphB proteins in macrophages at the site of injury. Given that EphB and ephrin-B proteins have also been implicated in regulating axon responses in spinal cord injury, 26 -28,55 this protein family may play a key role in various types of axon damage throughout the nervous system.…”

Neuroprotection of retinal ganglion cells by agonism of the beta but not the alpha oestrogen receptor in the axotomized retina of male and female mice

“…ERα has been shown to activate the same pathways as mGlu1 receptors (Spampinato et al, 2012), which are implicated in excitotoxic RGC degeneration (Liberatore et al, 2017). This aligns with the multifactorial nature of axotomyinduced RGC death, which activates multiple cell death pathways (Agudo et al, 2009) and includes excitotoxicity driven by axotomy-induced glutamate release (Vorwerk et al, 2004;Yoles & Schwartz, 1998;Yoles et al, 1997).…”

Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages

“…To understand the involvement of myeloid immune cells (resident and infiltrating) in the dynamic events occurring after retinal insult, we first studied this population in the adult retina under physiological and pathological conditions. We chose to use a model of retinal intoxication with glutamate (Schori et al, 2002; Schwartz and Kipnis, 2007), a common mediator of toxicity under neurodegenerative conditions (Dreyer et al, 1996; Shaw and Ince, 1997; Yoles and Schwartz, 1998; Dirnagl et al, 1999; Vorwerk et al, 1999; Gupta and Yücel, 2007). Surviving RGCs were assessed in this study 7 d after glutamate intoxication by immunostaining for Brn3a, a specific RGC marker (Nadal-Nicolás et al, 2009; Fig.…”

“…Our results suggest that coping with retinal injury requires a regulated immune response in which monocyte-derived macrophages are essential and intimate partners. Because the main experimental model of this study was glutamate intoxication, a phenomenon relevant to many CNS neurodegenerative disorders (Dreyer et al, 1996; Shaw and Ince, 1997; Yoles and Schwartz, 1998; Dirnagl et al, 1999; Vorwerk et al, 1999), our findings have far-reaching implications that extend beyond the eye. The outcomes of this study suggest the possible therapeutic potential of these cells as unique endogenous neuroprotective agents in treating retinal neuropathies as well as other CNS pathologies that involve neuronal loss.…”