# Determination of Cone Photoreceptor Fate

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $416,635

## Abstract

Photoreceptors (PRs) are highly specialized cells that transduce light energy into useful physiological signals.
In vertebrates, the ciliary PRs, rods and cones, initiate vision. The classical definition of rods and cones is
based upon the morphology of the outer segment, a membrane rich organelle specialized for the capture of
light and its processing so as to signal other retinal neurons. The range of light intensities over which PRs
operate is also a fundamental aspect of their definition, with rods operating in dim light and cones in brighter
light. Cones initiate our color and high acuity vision, with cones further defined by the wavelength sensitivity of
their opsin. Despite the high value we place on our vision, particularly our conemediated high acuity color
vision, we know very little about how cones are generated during development. This information would aid in
the efforts to replace them when they fail in many types of diseases leading to blindness. Current stem cell
methods are very limited in cone production, principally due to a lack of knowledge regarding the normal
developmental cues. New strategies are needed for these methods to produce enough cones to make this an
effective therapy.
 In addition to the benefits for therapeutic applications, knowledge of the mechanisms of PR genesis
would inform our understanding of the evolution and development of this important class of sensory neurons.
Given the high value of vision, PRs are under heavy selective pressure. This has resulted in a wide variety of
PR types, with a blurring of rod and cone definition using classically-defined morphology and physiology. In
addition, there are dramatic differences among species in the distribution of rods and the different types of
cones across the retina. For example, in humans, there is a small high acuity area, the fovea, where cones are
the only PR type. An understanding of how rods and cones are determined would allow for an appreciation of
some of the mechanisms that have driven these patterning, morphological, and physiological differences
across species.
 The focus of this grant will be the question of how cones choose their fate during development, utilizing
genomic data and modern methodologies. The starting point will be to define the transcription regulation of two
key genes required for cone genesis, Otx2 and Oc1, and the downstream events under control of Notch1, the
earliest known regulator of cone genesis, and then use these data to derive the cone gene regulatory
network(s).

## Key facts

- **NIH application ID:** 9843145
- **Project number:** 5R01EY029771-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** CONSTANCE L CEPKO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $416,635
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843145

## Citation

> US National Institutes of Health, RePORTER application 9843145, Determination of Cone Photoreceptor Fate (5R01EY029771-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843145. Licensed CC0.

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