Relationship between Sigma-1 receptor and BDNF in the visual system

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Glaucoma is an incurable optic neuropathy characterized by dysfunction and death of retinal ganglion cells (RGCs). Brain derived neurotrophic factor (BDNF) is an essential neurotrophin that supports RGC function and survival. Despite BDNF's importance, our knowledge of molecular mechanisms that modulate BDNF processing and secretion is incomplete. Sigma-1 receptor (S1R) is associated with increased BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and neuronal cell lines. Much less is known about the relationship between S1R and BDNF in the visual system. Here, we examine how S1R activation and deletion alter expression of mature BDNF (mBDNF) and proBDNF in retina and cultured optic nerve head (ONH) astrocytes. For S1R activation, the S1R agonist (+)-pentazocine (PTZ, 0.5 mg/kg) was administered by intraperitoneal injection to C57BL/6J mice, 3 times per week, for 5 weeks. Expression of proBDNF and mBDNF was also examined in S1R knockout and age-matched C57BL/6J mice. In vitro, cultured ONH astrocytes were treated with 3 μM PTZ for 24 h followed by collection of media and ONH astrocyte lysates. Results showed that treatment with (+)-PTZ increased mBDNF protein in both retina and hippocampus. In contrast, S1R deletion was associated with retinal mBDNF deficits. In ONH astrocytes S1R agonist (+)-PTZ significantly increased levels of secreted BDNF and proBDNF in cell lysates. These findings support a role for S1R in the modulation of BDNF levels within the retina and optic nerve head. Treatment with S1R agonists might provide benefit in diseases such as glaucoma by increasing BDNF levels from endogenous sources.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalExperimental eye research
Volume167
DOIs
StatePublished - Feb 1 2018

Fingerprint

Brain-Derived Neurotrophic Factor
Optic Disk
Astrocytes
Retina
Retinal Ganglion Cells
Inbred C57BL Mouse
Glaucoma
sigma-1 receptor
Hippocampus
Pentazocine
Optic Nerve Diseases
Nerve Growth Factors
Intraperitoneal Injections
Cell Survival

Keywords

  • BDNF
  • Glaucoma
  • Optic nerve head astrocytes
  • Retina

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Relationship between Sigma-1 receptor and BDNF in the visual system. / Mysona, Barbara A; Zhao, Jing; Smith, Sylvia B; Bollinger, Kathryn Elizabeth.

In: Experimental eye research, Vol. 167, 01.02.2018, p. 25-30.

Research output: Contribution to journalArticle

@article{5c432b11976e4b919d4b0406c17f18b1,
title = "Relationship between Sigma-1 receptor and BDNF in the visual system",
abstract = "Glaucoma is an incurable optic neuropathy characterized by dysfunction and death of retinal ganglion cells (RGCs). Brain derived neurotrophic factor (BDNF) is an essential neurotrophin that supports RGC function and survival. Despite BDNF's importance, our knowledge of molecular mechanisms that modulate BDNF processing and secretion is incomplete. Sigma-1 receptor (S1R) is associated with increased BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and neuronal cell lines. Much less is known about the relationship between S1R and BDNF in the visual system. Here, we examine how S1R activation and deletion alter expression of mature BDNF (mBDNF) and proBDNF in retina and cultured optic nerve head (ONH) astrocytes. For S1R activation, the S1R agonist (+)-pentazocine (PTZ, 0.5 mg/kg) was administered by intraperitoneal injection to C57BL/6J mice, 3 times per week, for 5 weeks. Expression of proBDNF and mBDNF was also examined in S1R knockout and age-matched C57BL/6J mice. In vitro, cultured ONH astrocytes were treated with 3 μM PTZ for 24 h followed by collection of media and ONH astrocyte lysates. Results showed that treatment with (+)-PTZ increased mBDNF protein in both retina and hippocampus. In contrast, S1R deletion was associated with retinal mBDNF deficits. In ONH astrocytes S1R agonist (+)-PTZ significantly increased levels of secreted BDNF and proBDNF in cell lysates. These findings support a role for S1R in the modulation of BDNF levels within the retina and optic nerve head. Treatment with S1R agonists might provide benefit in diseases such as glaucoma by increasing BDNF levels from endogenous sources.",
keywords = "BDNF, Glaucoma, Optic nerve head astrocytes, Retina",
author = "Mysona, {Barbara A} and Jing Zhao and Smith, {Sylvia B} and Bollinger, {Kathryn Elizabeth}",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.exer.2017.10.012",
language = "English (US)",
volume = "167",
pages = "25--30",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Relationship between Sigma-1 receptor and BDNF in the visual system

AU - Mysona, Barbara A

AU - Zhao, Jing

AU - Smith, Sylvia B

AU - Bollinger, Kathryn Elizabeth

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Glaucoma is an incurable optic neuropathy characterized by dysfunction and death of retinal ganglion cells (RGCs). Brain derived neurotrophic factor (BDNF) is an essential neurotrophin that supports RGC function and survival. Despite BDNF's importance, our knowledge of molecular mechanisms that modulate BDNF processing and secretion is incomplete. Sigma-1 receptor (S1R) is associated with increased BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and neuronal cell lines. Much less is known about the relationship between S1R and BDNF in the visual system. Here, we examine how S1R activation and deletion alter expression of mature BDNF (mBDNF) and proBDNF in retina and cultured optic nerve head (ONH) astrocytes. For S1R activation, the S1R agonist (+)-pentazocine (PTZ, 0.5 mg/kg) was administered by intraperitoneal injection to C57BL/6J mice, 3 times per week, for 5 weeks. Expression of proBDNF and mBDNF was also examined in S1R knockout and age-matched C57BL/6J mice. In vitro, cultured ONH astrocytes were treated with 3 μM PTZ for 24 h followed by collection of media and ONH astrocyte lysates. Results showed that treatment with (+)-PTZ increased mBDNF protein in both retina and hippocampus. In contrast, S1R deletion was associated with retinal mBDNF deficits. In ONH astrocytes S1R agonist (+)-PTZ significantly increased levels of secreted BDNF and proBDNF in cell lysates. These findings support a role for S1R in the modulation of BDNF levels within the retina and optic nerve head. Treatment with S1R agonists might provide benefit in diseases such as glaucoma by increasing BDNF levels from endogenous sources.

AB - Glaucoma is an incurable optic neuropathy characterized by dysfunction and death of retinal ganglion cells (RGCs). Brain derived neurotrophic factor (BDNF) is an essential neurotrophin that supports RGC function and survival. Despite BDNF's importance, our knowledge of molecular mechanisms that modulate BDNF processing and secretion is incomplete. Sigma-1 receptor (S1R) is associated with increased BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and neuronal cell lines. Much less is known about the relationship between S1R and BDNF in the visual system. Here, we examine how S1R activation and deletion alter expression of mature BDNF (mBDNF) and proBDNF in retina and cultured optic nerve head (ONH) astrocytes. For S1R activation, the S1R agonist (+)-pentazocine (PTZ, 0.5 mg/kg) was administered by intraperitoneal injection to C57BL/6J mice, 3 times per week, for 5 weeks. Expression of proBDNF and mBDNF was also examined in S1R knockout and age-matched C57BL/6J mice. In vitro, cultured ONH astrocytes were treated with 3 μM PTZ for 24 h followed by collection of media and ONH astrocyte lysates. Results showed that treatment with (+)-PTZ increased mBDNF protein in both retina and hippocampus. In contrast, S1R deletion was associated with retinal mBDNF deficits. In ONH astrocytes S1R agonist (+)-PTZ significantly increased levels of secreted BDNF and proBDNF in cell lysates. These findings support a role for S1R in the modulation of BDNF levels within the retina and optic nerve head. Treatment with S1R agonists might provide benefit in diseases such as glaucoma by increasing BDNF levels from endogenous sources.

KW - BDNF

KW - Glaucoma

KW - Optic nerve head astrocytes

KW - Retina

UR - http://www.scopus.com/inward/record.url?scp=85034021060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034021060&partnerID=8YFLogxK

U2 - 10.1016/j.exer.2017.10.012

DO - 10.1016/j.exer.2017.10.012

M3 - Article

C2 - 29031856

AN - SCOPUS:85034021060

VL - 167

SP - 25

EP - 30

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

ER -