Restoring Light Sensitivity in Blind Retinae Using a Photochromic AMPA Receptor Agonist.
Retinal degenerative diseases can have many possible causes and are currently difficult to treat. As an alternative to therapies that require genetic manipulation or the implantation of electronic devices, photopharmacology has emerged as a viable approach to restore visual responses. Here, we present a new photopharmacological strategy that relies on a photoswitchable excitatory amino acid, ATA. This freely diffusible molecule selectively activates AMPA receptors in a light-dependent fashion. It primarily acts on amacrine and retinal ganglion cells, although a minor effect on bipolar cells has been observed. As such, it complements previous pharmacological approaches based on photochromic channel blockers and increases the potential of photopharmacology in vision restoration.
Center of Integrated Protein Science Munich (CIPSM) at the Department of Chemistry Ludwig-Maximilians-Universität München , Munich 81377, Germany.
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Laprell
Center of Integrated Protein Science Munich (CIPSM) at the Department of Chemistry Ludwig-Maximilians-Universität München , Munich 81377, Germany.
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Hüll
Center of Integrated Protein Science Munich (CIPSM) at the Department of Chemistry Ludwig-Maximilians-Universität München , Munich 81377, Germany.
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Stawski
Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München , Munich 81377, Germany.
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Schön
Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München , Munich 81377, Germany.
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Michalakis
Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München , Munich 81377, Germany.
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Biel
Center of Integrated Protein Science Munich (CIPSM) at the Department of Chemistry Ludwig-Maximilians-Universität München , Munich 81377, Germany.
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Sumser
Center of Integrated Protein Science Munich (CIPSM) at the Department of Chemistry Ludwig-Maximilians-Universität München , Munich 81377, Germany.
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Trauner
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001766:Blindness / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D018682:GABA Agents / Q000494:pharmacology; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010721:Phosphinic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D017299:Rod Opsins / Q000172:deficiency / Q000235:genetics; D054830:Sesterterpenes; D020741:rho GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics; D000097806:GluK2 Kainate Receptor; D000099210:Melanopsin
D054815:Cyclic Nucleotide-Gated Cation Channels; D018682:GABA Agents; D010721:Phosphinic Acids; D010852:Picrotoxin; D011725:Pyridines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017299:Rod Opsins; D054830:Sesterterpenes; D020741:rho GTP-Binding Proteins; D000097806:GluK2 Kainate Receptor; D000099210:Melanopsin; C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; C518237:Cnga3 protein, mouse; C022961:picrotoxinin
AMPA receptors; ATA; Photopharmacology; photochromic ligand; retinal degeneration