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J. W. Stoddard, P. Francis; Characterization of SSRI Action in the Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3321.
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Brain-derived neurotrophic factor (BDNF) is a growth factor implicated in the survival and function of neurons. Multiple investigations have demonstrated the ability of BDNF to rescue photoreceptors from degenerating in animal models of age-related macular degeneration and inherited retinal disease. Selective serotonin reuptake inhibitors (SSRIs) act to increase the amount of serotonin in the extracellular space around neurons. Recent evidence suggests SSRI antidepressants mediate their beneficial effects in part by elevating BDNF expression in the adult brain. We hypothesize that SSRIs act in the same manner in the retina to elevate BDNF levels. The purpose of this study is to investigate the actions of SSRIs on serotonin physiology and BDNF signaling in the retina.
Total RNA was isolated from human RPE and ARPE-19 cells. Reverse transcriptase (RT)-PCR for BDNF, 5-HT (serotonin) receptors and the 5-HT transporter was performed. ARPE-19 cells cultured in DMEM/F12 serum free media in 12-well plates were exposed to fluoxetine (10um) and serotonin (100um) at multiple time points. Expression of total BDNF mRNA was analyzed via real-time PCR and total secreted BDNF protein was quantified via ELISA.
RT-PCR using exon-spanning primers yielded products of the predicted size in RPE and ARPE-19 cells for 5-HT1a, 5-HT6, and 5-HT7 receptors, the 5-HT transporter and BDNF. The 5-HT2a receptor was only present on ARPE-19 cells. In cells exposed to fluoxetine and serotonin an increase in BDNF mRNA was observed after 48 hours and persisted up to one week while an increase in secreted BDNF protein was detected by day 12.
Our initial experiments have demonstrated that RPE cells possess the molecular machinery to respond to the actions of SSRI’s and serotonin. Furthermore, our data may suggest that SSRI’s have therapeutic potential in treating retinal degenerations by increasing retinal BDNF levels.
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