# Phototransduction and Signaling in Photoreceptors

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $409,375

## Abstract

PROJECT SUMMARY
 There have been great advances over the past 40 years in understanding how light initiates vision in
rod and cone photoreceptors of the eye. Not only is the sequence of events in this process known, but the
genes coding for the key phototransduction proteins have also been cloned. Mutations of many of these
genes are found to be associated with various vision-impairing diseases.
 Phototransduction starts from the visual pigment. A little over ten years ago, we made major
advances by showing that the dark spontaneous activity of rod and cone pigments indeed comes from
canonical isomerization of the pigment albeit being driven by thermal instead of light energy. We developed
a physicochemical theory that is able to predict quantitatively the 107-fold range in thermal activity across
canonical (i.e., native) rod and cone pigments in the visible spectrum as well as that of a man-made, hybrid
pigment with both rod-pigment-like and cone-pigment-like properties. Considering visual pigments’
fundamental importance in both basic and clinical science, we propose in Aim 1 to understand native
pigments further. In particular, we would like to examine the effect of protonation (found in the great majority
of L, M and S- pigments, which detect visible light) versus non-protonation (found in mouse S(UV)-sensitive
pigment and some others) at the Schiff-base linkage between apo-opsin and 11-cis-retinal on the
spontaneous isomerization of a pigment. There is suggestion from chemistry by others that unprotonated
pigments are much noisier in darkness. Additionally, an unusual property of S-pigments is that they belong
to two distinct evolutionary sub-groups: SWS1 (minor subgroup) and SWS2 (major subgroup). In preliminary
experiments during this grant period, we have found some evidence to suggest that SWS1 pigments are
much noisier in darkness. We propose in Aim 2 to address this question closely and quantitatively by
examining several pigments belonging to one or the other subgroup. Finally, unlike rod pigments, cone
pigments have some tendency to re-dissociate spontaneously in darkness into apo-opsin and 11-cis-retinal
(i.e., without isomerization). Importantly, because apo-opsin has weak constitutive activity, it triggers
transduction to produce electrical noise even in darkness. Most recently, we found surprisingly that, in fully
dark-adapted goldfish L(red)-cones, the fractional apo-opsin content is as high as ~30%, although only ~3%
in green (M) cones and negligible in blue (S) cones. In Aim 3, we would like to know whether mammalian
cones when fully dark-adapted also have a significant amount of apo-opsin. We shall examine several
species, including marmoset (a primate) and, if available, macaque. Techniques involved primarily suction-
pipette recording and microspectrophotometry from native cones.

## Key facts

- **NIH application ID:** 10881126
- **Project number:** 2R01EY006837-34A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** KING-WAI YAU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $409,375
- **Award type:** 2
- **Project period:** 1987-02-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881126

## Citation

> US National Institutes of Health, RePORTER application 10881126, Phototransduction and Signaling in Photoreceptors (2R01EY006837-34A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10881126. Licensed CC0.

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