September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Sigma-1 receptor mediated secretion of BDNF by optic nerve head astrocytes
Author Affiliations & Notes
  • Barbara Ann Mysona
    Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States
    James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States
  • Jing Zhao
    Department of Ophthalmology, Medical College of Georgia, Augusta, Georgia, United States
    James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States
  • Sylvia B Smith
    Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States
    James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States
  • Kathryn E Bollinger
    Department of Ophthalmology, Medical College of Georgia, Augusta, Georgia, United States
    James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   Barbara Mysona, None; Jing Zhao, None; Sylvia Smith, None; Kathryn Bollinger, None
  • Footnotes
    Support  NIH grant K08EY021758, American Glaucoma Society young clinician scientist award
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4212. doi:
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    • Get Citation

      Barbara Ann Mysona, Jing Zhao, Sylvia B Smith, Kathryn E Bollinger; Sigma-1 receptor mediated secretion of BDNF by optic nerve head astrocytes. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4212.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Sigma-1 receptor (SR1) is a membrane associated molecular chaperone protein expressed in retinal neurons and glia. SR1 agonists are neuroprotective in experimental models of neurodegenerative diseases, including diabetic retinopathy, Alzheimer’s and Parkinson’s disease. The mechanism for neuroprotection within brain and retina is unknown. However, SR1 is known to modulate many cellular processes, including responses to oxidative and endoplasmic reticulum (ER) stress and intracellular Ca2+ signaling. In addition, SR1 mediates secretion of brain derived neurotrophic factor (BDNF) from neuronal and glial cultures. BDNF is a critical factor for neuronal survival and differentiation. Therefore, we chose to investigate whether activation of SR1 induces release of BDNF from retinal tissues and optic nerve head (ONH) astrocytes.

Methods : C57BL6 mice were treated by intraperitoneal injection of the SR1 specific agonist (+)-pentazocine (PTZ), 0.5 mg/kg, 3 times a week for 5 weeks. Age-matched C57BL6 controls and SR1 knockout mice were also used. Retina and hippocampus tissues were harvested and analyzed by Western blot and immunohistochemistry for expression of SR1 and BDNF. Primary ONH astrocytes were isolated and cultured from 3-5 day old Sprague Dawley rat pups. ONH astrocytes were treated in presence or absence of the ER stress inducer tunicamycin (5 ng/ml to 5 ug/ml) with or without PTZ (3µM). After 24 hours, media was analyzed by ELISA for secreted BDNF. Cell lysates were analyzed for protein expression of CHOP, SR1, and BDNF.

Results : After treatment of C57BL6 mice with PTZ, BDNF levels were increased in hippocampus but not retina while SR1 levels remained unchanged. Retinas from SR1 knockout mice had less BDNF than C57BL6 counterparts. Treatment of ONH astrocytes with tunicamycin (5 ug/ml and 500 ng/ml) blocked secretion of BDNF and increased expression of CHOP while SR1 levels remained unchanged. In contrast, treatment with PTZ increased secretion of BDNF.

Conclusions : SR1 mediated release of BDNF may be organ and cell specific. Decreased BDNF observed in SR1 knockout retinas supports a link between SR1 and BDNF secretion. Although treatment with PTZ did not increase BDNF in C57BL6 retinas, PTZ treatment did stimulate BDNF secretion by ONH astrocytes. PTZ-mediated release of BDNF from ONH astrocytes may prove to be neuroprotective in conditions associated with retinal ganglion cell degeneration such as glaucoma.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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