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Renee C Ryals, Shreya Datta, Aaron Coyner, Halkanae Gemechu, Alex Chu, Yuquan Wen, Mark E Pennesi; Potential of 5-HT3 receptor modulation for protection of light induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):213.
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© ARVO (1962-2015); The Authors (2016-present)
5-HT3 antagonists are widely used for antiemetic therapy and are being investigated as therapeutic options for a variety of behavioral disorders. Our previous results suggest that modulation of 5-HT1A and 5-HT2A receptors can protect the retina from light induced retinopathy. The purpose of this study was to determine if the serotonin 5-HT3 receptor is located in the retina and if modulation of the receptor protects the retina from light induced retinopathy.
Total membrane protein and plasma membrane protein was extracted from C57BL/6 retinas. SDS-PAGE electrophoresis was performed and blots were probed with an antibody specific to 5-HT3A (Alomone Labs). To test if 5-HT3 receptor modulation is neuroprotective, two-month-old BALB/c mice were placed in a 12/12 hour alternate light-dark cycle room. For induction of retinopathy, dark-adapted mice were placed in a custom light-damage box with 4 CFL bulbs (42 watts, 6500K color temperature). Mice were exposed to 10,000 lux of light for 1-hour. Palonosetron (0.2 mg/kg), a 5-HT3 antagonist, and m-Chlorophenylbiguanide (m-CPBG) (10 mg/kg), a 5-HT3 agonist, were injected intraperitoneally 48 hours, 24 hours and 0 hours prior to bright light exposure as well as 24 hours and 48 hours after bright light exposure. To evaluate neuroprotection, linear scans of the retina were acquired using spectral domain-optical coherence tomography (Bioptigen, Inc.). Retinal thickness was quantified on manually segmented images using custom software written in IGOR Pro. Retinal function was measured by full-field electroretinogram.
Western blots demonstrated 5-HT3 receptor expression in total membrane and plasma membrane protein extract from mouse retina. SD-OCT images showed no preservation of the outer nuclear layer in palonosetron and m-CPBG injected mice. In addition, maximum scotopic a-wave and b-wave amplitudes of palonosetron and m-CPBG injected mice were not statistically different (p<0.05) from saline injected mice.
5-HT3 receptors are present in the retina. However, intraperitoneal injection with a selective 5-HT3 agonist, m-CPBG, or a selective antagonist, palonosetron, did not result in neuroprotection. This does not provide evidence that the 5-HT3 ligand-gated ion channel plays a role in neuroprotection. Neuroprotection observed by 5-HT modulators may be G protein-coupled receptor specific.
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