# Bioluminescent Multi-Characteristic Opsin for simultaneous optical stimulation and large-scale monitoring of the visual system

> **NIH NIH R01** · NANOSCOPE TECHNOLOGIES, LLC · 2020 · $387,500

## Abstract

The optogenetic stimulation strategy, which is an alternative to electrical stimulation and now under clinical trial
for vision restoration in retinal degenerative diseases, involves simple intravitreal injection of safe AAV-carrying
opsin to photosensitize higher order retinal neurons. Compared with other strategies, optogenetic method is
cell-specific and provides higher resolution. Our optogenetic studies in dry-AMD mice model suggests that
degenerated retina can be made highly photosensitive, enabling vision restoration at low light level.
Furthermore, our preclinical studies have shown that the visually guided behavior deteriorated with progressive
degeneration, which recovered to more non-degenerated level after optogenetic treatment. Though primary
visual cortex is known to maintain its retinotopy in subjects with retinal degeneration despite prolonged visual
loss, detailed knowledge of how optogenetic sensitization of higher order neurons manifests in restoration of
visual cortical activity is currently lacking. Thus, there is a need for mapping changes in the visual cortical
activities as progression of retinal degeneration and subsequent vision restoration by optogenetic sensitization
of retina occurs. The goal of this study is to develop and characterize tools for simultaneous optical modulation
and imaging of retinal and cortical activities using spectrally-separated activation and detection channels. To
address this goal, we propose to use newly developed voltage-sensitive bioluminescence assay instead of
fluorescence in order to allow simultaneous long-term cortical imaging upon visual stimulation using multi-
characteristic opsin (MCO). This will enable us to modulate neural activity in retina and image visual cortex
with high temporal and spatial resolution, providing details about disease progression and restoration. The
innovativeness of our proposal includes bioluminescent membrane voltage indicator to measure neural activity
in long-term studies with high temporal resolution. This new bioluminescent technique does not require an
additional potentially phototoxic external excitation source (as used for fluorescence). Further innovativeness
includes simultaneous measurements of cortical activities and behavior in response to visual stimulation during
retinal degeneration and vision restoration. Towards this goal we will: (i) Demonstrate functioning of
Bioluminescent MCO and hardware for stimulation and bioluminescent neural activity monitoring; (ii) Quantify
changes in visual cortical activities during progression of retinal photoreceptor degeneration by bMCO using
head-mountable sCMOS-camera; and (iii) Evaluate restoration of visual cortical activities upon re-
photosensitization of degenerated retina by intravitreal injection of MCO. Success of this proposal will lead to
development of a modular and scalable interface system with the capability to serve a multiplicity of
applications to modulate and monitor large-scale activit...

## Key facts

- **NIH application ID:** 9961597
- **Project number:** 5R01EY028216-03
- **Recipient organization:** NANOSCOPE TECHNOLOGIES, LLC
- **Principal Investigator:** Samarendra Kumar Mohanty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961597

## Citation

> US National Institutes of Health, RePORTER application 9961597, Bioluminescent Multi-Characteristic Opsin for simultaneous optical stimulation and large-scale monitoring of the visual system (5R01EY028216-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9961597. Licensed CC0.

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