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Keith Michaels, Anastasiya Johnson, Michael Gale, Sean Davin, Anupam Garg, Michael Andrews, Hope Titus, Mark Pennesi; Serotonin Receptor Modulation and Neuroprotection in Models of Light Damage and Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3270.
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© ARVO (1962-2015); The Authors (2016-present)
To fully characterize the expression of serotonin (5-HT) receptors in the retina and to assess the potential of 5-HT receptor modulation to decrease retinal cell death in rodent models of light-damage and retinal degeneration.
In situ hybrization (ISH) was performed on paraffin-embedded mouse retina using RNAscope® 2.0. Probes designed to target 5-HT receptor and transporter mRNA transcripts were created by Advanced Cell Diagnostics, Inc. Light-damage was induced by exposing Balb/c mice to 4 hours of light emitted by 4 CFL bulbs (42 watts; 6500K color temperature; 9000 lux total intensity). Balb/c mice were injected with various concentrations of 8-OH-DPAT (a 5-HT1A receptor agonist), SB-269,970 (a 5-HT7 receptor antagonist), or saline. Mice were injected 48, 24, and 0 hours before exposure and 24 and 48 hours after. Linear, annular, and rectangular scans were acquired using a Bioptigen spectral domain optical coherence tomography device, as previously described. The linear and annular scans were manually segmented, using a previously published method. The segmentation results of the treated, naïve, and saline injected mice were compared.
We previously described the expression of 5-HT receptors and 5-HT transporter in the rodent brain and retina using RT-PCR, western blot, and immunohistochemistry. ISH demonstrated the localization of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, and 5-HTT mRNA transcripts in the mouse retina. 5-HT1A, 5-HT1B, and 5-HT1D were detected in the ganglion cell layer (GCL) and inner nuclear layer (INL). 5-HT1A and 5-HT1D were also expressed in the outer nuclear layer (ONL). 5-HT1F and 5-HTT were weakly expressed in the GCL and INL. Exposure to 9000 lux induced uniform damage in the control Balb/c mice. Segmentation analysis showed considerable differences between the average total retinal (TR) and receptor plus (REC+) thicknesses of the groups: naïve (TR = 200.8 µm; REC+ = 119.2 µm), 1.0 mg/kg 8-OH-DPAT (TR = 178.0 µm; REC+ = 90.3 µm), 12.5 mg/kg SB-269,970 (TR = 135.8 µm; REC+ = 48.4 µm), 1.25 mg/kg SB-269,970 (TR = 128.5 µm; REC+ = 41.5 µm) and 0.9% saline (TR = 122.2 µm; 40.5 µm REC+).
8-OH-DPAT is effective in preserving retinal thickness in the Balb/c light-damage model. Although SB-269,970 at the highest concentration shows slight protection of the retina when compared to the saline control, it is considerably less effective than 8-OH-DPAT.
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