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Kanika Ghai, Pradoldej Sompol, Keqiang Ye, P. Michael Iuvone; An N-acetylserotonin Derivative Mitigates The Effects Of Light-induced Retinal Damage. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5447.
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In the retina, BDNF has been shown to mitigate light-induced apoptosis of adult mouse photoreceptors (LaVail 1998). However, the neuroprotective effects of this molecule in the retina have been difficult to replicate due to various factors including short half-life, low rate of transport across the blood-brain barrier, actions on p75NTR, and high expense which limits its clinical development. Thus, we looked for alternative neuroprotective substitutes for BDNF that selectively activate TrkB. Recently, it was shown that N-acetylserotonin (NAS) directly activates TrkB in cultured cells and activates TrkB in the retina following systemic administration (Jang et al 2010). Endogenous NAS generates a circadian rhythm of TrkB activation in the retina. The aim of this study was to investigate whether a stable chemical analog of NAS [NAS (D)] also has neuroprotective effects in the retina, similar to those seen with BDNF.
Balb/C mice were administered intraperitoneal injections of NAS(D) (20 mg/kg) once daily for 5 consecutive days. On day 3, they were exposed to bright light (8000lux) in a cylindrical light damage apparatus for 1 hr and injected with NAS(D) before and after light exposure. Electroretinogram analyses were conducted at various time points after bright light exposure and eyes were harvested 3 weeks later to determine the extent of cellular and tissue damage.
We found that bright light exposure reduces a-wave responses in both vehicle and NAS(D) treated mice but NAS(D)-treated mice have better preservation of a-wave responses compared to vehicle-treated mice. Further, NAS(D)-treated mice have better preservation of b-wave responses which is conserved over time. NAS(D)-treated mice also have better preserved outer nuclear layers than vehicle-treated mice, especially in the inferior regions of the retina.
Our findings suggest that a stable NAS derivative has neuroprotective effects and partially preserves outer nuclear layer morphology as well as ERG responses in retinas exposed to acute bright light.
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