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Publication : New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

First Author  Schur RM Year  2018
Journal  FASEB J Volume  32
Issue  6 Pages  3289-3300
PubMed ID  29401616 Mgi Jnum  J:267644
Mgi Id  MGI:6268874 Doi  10.1096/fj.201701250R
Citation  Schur RM, et al. (2018) New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models. FASEB J 32(6):3289-3300
abstractText  No clinically approved therapies are currently available that prevent the onset of photoreceptor death in retinal degeneration. Signaling between retinal neurons is regulated by the release and uptake of neurotransmitters, wherein GABA is the main inhibitory neurotransmitter. In this work, novel 3-chloropropiophenone derivatives and the clinical anticonvulsants tiagabine and vigabatrin were tested to modulate GABA signaling and protect against light-induced retinal degeneration. Abca4(-/-)Rdh8(-/-) mice, an accelerated model of retinal degeneration, were exposed to intense light after prophylactic injections of one of these compounds. Imaging and functional assessments of the retina indicated that these compounds successfully protected photoreceptor cells from degeneration to maintain a full-visual-field response. Furthermore, these compounds demonstrated a strong safety profile in wild-type mice and did not compromise visual function or damage the retina, despite repeated administration. These results indicate that modulating inhibitory GABA signaling can offer prophylactic protection against light-induced retinal degeneration.-Schur, R. M., Gao, S., Yu, G., Chen, Y., Maeda, A., Palczewski, K., Lu, Z.-R. New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.
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