Journal
STEM CELL RESEARCH & THERAPY
Volume 10, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13287-019-1363-1
Keywords
TRPV1; PKA; Osmotic stress; Human-induced pluripotent stem cells; hiPSC; Retinal ganglion cells; RGC
Funding
- Ministry of Science and Technology (MOST) [106-2633-B-009-001, 107-2633-B-009-003, MOST 106-2319-B-001-003, MOST 106-2119-M-010-001, MOST 106-3114-B-010-002, MOST 107-2321-B-010-007]
- Academia Sinica [MOST 106-0210-01-15-02, MOST 107-0210-01-19-01]
- Tri-Service General Hospital [TSGH-C107-090]
- National Defense Medical Center [MAB-108-049]
- Taipei Veterans General Hospital [V106E-004-2, V106C-001, V107C-139, V107E-002-2]
- VGH [VTA107-V1-5-1]
- TSGH [VTA107-V1-5-1]
- NDMC [VTA107-V1-5-1]
- TVGH
- NTUH [VN106-02, VN107-16]
- Department of Health Cancer Center Research of Excellence [MOHW106-TDU-B-211-113001, MOHW107-TDU-B-211-123001]
- Yen-Tjing-Ling Medical Foundation [CI-102/105]
- National Health Research Institutes of Taiwan [NHRI-EX106-10621BI, NHRI-EX107-10621BI]
- Cancer Progression Research Center of National Yang-Ming University from The Featured Areas Research Center Program
- AS [VTA107-V1-5-1]
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BackgroundTransient receptor potential vanilloid 1 (TRPV1), recognized as a hyperosmolarity sensor, is a crucial ion channel involved in the pathogenesis of neural and glial signaling. Recently, TRPV1 was determined to play a role in retinal physiology and visual transmission. In this study, we sought to clarify the role of TRPV1 and the downstream pathway in the osmotic stress-related retina ganglion cell (RGC) damage.MethodsFirst, we modified the RGC differentiation protocol to obtain a homogeneous RGC population from humaninduced pluripotent stem cells (hiPSCs). Subsequently, we induced high osmotic pressure in the hiPSC-derived RGCs by administering NaCl solution and observed the behavior of the TRPV1 channel and its downstream cascade.ResultsWe obtained a purified RGC population from the heterogeneous retina cell population using our modified method. Our findings revealed that TRPV1 was activated after 24h of NaCl treatment. Upregulation of TRPV1 was noted with autophagy and apoptosis induction. Downstream protein expression analysis indicated increased phosphorylation of CREB and downregulated brain-derived neurotrophic factor (BDNF). However, hyperosmolarity-mediated defective morphological change and apoptosis of RGCs, CREB phosphorylation, and BDNF downregulation were abrogated after concomitant treatment with the PKA inhibitor H89.ConclusionCollectively, our study results indicated that the TRPV1-PKA pathway contributed to cellular response under high levels of osmolarity stress; furthermore, the PKA inhibitor had a protective effect on RGCs exposed to this stress. Therefore, our findings may assist in the treatment of eye diseases involving RGC damage.
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