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

Abstract

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.

• Authors: Rebecca M Schur, Songqi Gao, Guanping Yu, Yu Chen, Akiko Maeda, Krzysztof Palczewski, Zheng-Rong Lu
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 32 Issue 6 Pg. 3289-3300 (06 2018) ISSN: 1530-6860 [Electronic] United States
• PMID: 29401616 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ATP-Binding Cassette Transporters
• Abca4 protein, mouse
• Propiophenones
• gamma-Aminobutyric Acid
• Alcohol Oxidoreductases
• Rdh8 protein, mouse

Topics

• ATP-Binding Cassette Transporters (genetics, metabolism)
• Alcohol Oxidoreductases (genetics, metabolism)
• Animals
• Light (adverse effects)
• Mice
• Mice, Knockout
• Photoreceptor Cells, Vertebrate (metabolism, pathology)
• Propiophenones (chemistry, pharmacology)
• Retinal Degeneration (drug therapy, genetics, metabolism)
• gamma-Aminobutyric Acid (metabolism)