title: Block of gap junctions eliminates aberrant activity and restores light responses during retinal degeneration.
abstract: Retinal degeneration leads to progressive photoreceptor cell death, resulting in vision loss. Subsequently, inner retinal neurons develop aberrant synaptic activity, compounding visual impairment. In retinal ganglion cells, light responses driven by surviving photoreceptors are obscured by elevated levels of aberrant spiking activity. Here, we demonstrate in rd10 mice that targeting disruptive neuronal circuitry with a gap junction antagonist can significantly reduce excessive spiking. This treatment increases the sensitivity of the degenerated retina to light stimuli driven by residual photoreceptors. Additionally, this enhances signal transmission from inner retinal neurons to ganglion cells, potentially allowing the retinal network to preserve the fidelity of signals either from prosthetic electronic devices, or from cells optogenetically modified to transduce light. Thus, targeting maladaptive changes to the retina allows for treatments to use existing neuronal tissue to restore light sensitivity, and to augment existing strategies to replace lost photoreceptors.
authors.affiliation: Department of Ophthalmology, Weill Medical College of Cornell University, Burke Medical Research Institute, White Plains, New York 10605, USA.
authors.forename: Abduqodir H
authors.initials: AH
authors.lastname: Toychiev
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Yee
authors.forename: Botir T
authors.initials: BT
authors.lastname: Sagdullaev
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008027:Light; D055537:Light Signal Transduction / Q000187:drug effects* / Q000235:genetics; D008469:Meclofenamic Acid / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D010786:Photoreceptor Cells / Q000502:physiology; D012162:Retinal Degeneration / Q000188:drug therapy / Q000235:genetics*; D012165:Retinal Ganglion Cells / Q000502:physiology; D014785:Vision, Ocular / Q000187:drug effects / Q000235:genetics
chemical_list: D008469:Meclofenamic Acid; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse