PMID- 29031856 OWN - NLM STAT- MEDLINE DCOM- 20181005 LR - 20231213 IS - 1096-0007 (Electronic) IS - 0014-4835 (Print) IS - 0014-4835 (Linking) VI - 167 DP - 2018 Feb TI - Relationship between Sigma-1 receptor and BDNF in the visual system. PG - 25-30 LID - S0014-4835(17)30483-9 [pii] LID - 10.1016/j.exer.2017.10.012 [doi] 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 muM 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. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Mysona, Barbara A AU - Mysona BA AD - James and Jean Culver Vision Discovery Institute, Augusta, GA, 30912, United States; Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA, 30912, United States; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, United States. FAU - Zhao, Jing AU - Zhao J AD - James and Jean Culver Vision Discovery Institute, Augusta, GA, 30912, United States; Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA, 30912, United States; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, United States. FAU - Smith, Sylvia AU - Smith S AD - James and Jean Culver Vision Discovery Institute, Augusta, GA, 30912, United States; Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA, 30912, United States; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, United States. FAU - Bollinger, Kathryn E AU - Bollinger KE AD - James and Jean Culver Vision Discovery Institute, Augusta, GA, 30912, United States; Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA, 30912, United States; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, United States. Electronic address: kbollinger@gru.edu. LA - eng GR - K08 EY021758/EY/NEI NIH HHS/United States GR - R01 EY027406/EY/NEI NIH HHS/United States GR - R01 EY028103/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20171012 PL - England TA - Exp Eye Res JT - Experimental eye research JID - 0370707 RN - 0 (Analgesics, Opioid) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, sigma) RN - RP4A60D26L (Pentazocine) SB - IM MH - Analgesics, Opioid/pharmacology MH - Animals MH - Astrocytes/*metabolism MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Glaucoma/metabolism MH - Injections, Intraperitoneal MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Optic Disk/cytology MH - Pentazocine/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, sigma/agonists/*physiology MH - Retina/*metabolism MH - Sigma-1 Receptor PMC - PMC5757370 MID - NIHMS920758 OTO - NOTNLM OT - BDNF OT - Glaucoma OT - Optic nerve head astrocytes OT - Retina EDAT- 2017/10/17 06:00 MHDA- 2018/10/06 06:00 PMCR- 2019/02/01 CRDT- 2017/10/17 06:00 PHST- 2017/07/10 00:00 [received] PHST- 2017/10/10 00:00 [revised] PHST- 2017/10/11 00:00 [accepted] PHST- 2017/10/17 06:00 [pubmed] PHST- 2018/10/06 06:00 [medline] PHST- 2017/10/17 06:00 [entrez] PHST- 2019/02/01 00:00 [pmc-release] AID - S0014-4835(17)30483-9 [pii] AID - 10.1016/j.exer.2017.10.012 [doi] PST - ppublish SO - Exp Eye Res. 2018 Feb;167:25-30. doi: 10.1016/j.exer.2017.10.012. Epub 2017 Oct 12.