Photopharmacologic Vision Restoration Reduces Pathological Rhythmic Field Potentials in Blind Mouse Retina

Katharina Hüll, Tyler Benster, Michael B. Manookin, Dirk Trauner, Russell N. Van Gelder, Laura Laprell

Research output: Contribution to journalArticle

Abstract

Photopharmacology has yielded compounds that have potential to restore impaired visual responses resulting from outer retinal degeneration diseases such as retinitis pigmentosa. Here we evaluate two photoswitchable azobenzene ion channel blockers, DAQ and DAA for vision restoration. DAQ exerts its effect primarily on RGCs, whereas DAA induces light-dependent spiking primarily through amacrine cell activation. Degeneration-induced local field potentials remain a major challenge common to all vision restoration approaches. These 5-10 Hz rhythmic potentials increase the background firing rate of retinal ganglion cells (RGCs) and overlay the stimulated response, thereby reducing signal-to-noise ratio. Along with the bipolar cell-selective photoswitch DAD and second-generation RGC-targeting photoswitch PhENAQ, we investigated the effects of DAA and DAQ on rhythmic local field potentials (LFPs) occurring in the degenerating retina. We found that photoswitches targeting neurons upstream of RGCs, DAA (amacrine cells) and DAD (bipolar cells) suppress the frequency of LFPs, while DAQ and PhENAQ (RGCs) had negligible effects on frequency or spectral power of LFPs. Taken together, these results demonstrate remarkable diversity of cell-type specificity of photoswitchable channel blockers in the retina and suggest that specific compounds may counter rhythmic LFPs to produce superior signal-to-noise characteristics in vision restoration.

Original languageEnglish (US)
Number of pages1
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Sep 19 2019

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Retinal Ganglion Cells
Retina
Amacrine Cells
Retinal Diseases
Retinal Degeneration
Retinitis Pigmentosa
Signal-To-Noise Ratio
Ion Channels
Noise
Neurons
Light
DAQ

ASJC Scopus subject areas

  • General

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Photopharmacologic Vision Restoration Reduces Pathological Rhythmic Field Potentials in Blind Mouse Retina. / Hüll, Katharina; Benster, Tyler; Manookin, Michael B.; Trauner, Dirk; Van Gelder, Russell N.; Laprell, Laura.

In: Scientific reports, Vol. 9, No. 1, 19.09.2019.

Research output: Contribution to journalArticle

Hüll, Katharina ; Benster, Tyler ; Manookin, Michael B. ; Trauner, Dirk ; Van Gelder, Russell N. ; Laprell, Laura. / Photopharmacologic Vision Restoration Reduces Pathological Rhythmic Field Potentials in Blind Mouse Retina. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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