# Understanding how photoswitches restore visual function in blindness

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $271,879

## Abstract

PROJECT SUMMARY
Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are blinding diseases caused by the
degeneration of rods and cones, leaving the rest of the visual system intact but unable to respond to light. A
synthetic chemical photoswitch, named DENAQ, can restore visual responses in blind mouse models of RP.
Previous studies showed that DENAQ imparts light-sensitivity on action potential firing in retinal ganglion cells
(RGC), but how this occurs is unclear. The goal of this project is to elucidate the mechanism of DENAQ
photosensitization, crucial for enabling discovery of improved drug candidates and for optimizing photo-
stimulation strategies for vision restoration. The first aim is to understand why DENAQ selectively
photosensitizes retinas from mice with dead rods and cones while having no effect on healthy retinas with
intact rods and cones. We will test the hypothesis that degeneration leads to enhanced entry of DENAQ into
RGCs and/or enhanced action on ion channels underlying spontaneous firing in RGCs. The second aim is to
identify which RGCs are photosensitized by DENAQ. In the healthy retina, some RGCs fire at light onset, some
at offset, and some at onset and offset. Studies will determine which are photosensitized by DENAQ, and
whether local degeneration of rods and cones leads to spatially constrained RGC photosensitization, of
particular relevance for AMD, a localized degenerative disease. Other studies will reveal whether DENAQ
photosensitization applies to human RGCs in tissue samples obtained during surgical retinectomy. The third
aim is to exploit our findings to optimize vision restoration. Information about the ion channels targeted by
DENAQ will enable development of more specific photoswitches. Subcellular localization of these channels in
RGCs will enable more spatially-precise photo-control. Finally imaging studies in vivo will reveal signals
transmitted from the DENAQ-treated retina to the brain of blind mice, validating the functional integrity of the
visual system and providing a platform for optimizing retinal stimulation patterns to best recapitulate normal
visual responses.

## Key facts

- **NIH application ID:** 10212754
- **Project number:** 3R01EY024334-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** RICHARD H KRAMER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $271,879
- **Award type:** 3
- **Project period:** 2015-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212754

## Citation

> US National Institutes of Health, RePORTER application 10212754, Understanding how photoswitches restore visual function in blindness (3R01EY024334-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10212754. Licensed CC0.

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