# Novel model systems for the study of cone disorders and other heritable retinal diseases

> **NIH NIH U24** · BAYLOR COLLEGE OF MEDICINE · 2021 · $150,000

## Abstract

Project Summary/Abstract
Retinal degeneration diseases are a common cause of untreatable blindness worldwide, affecting the
lives of millions. The only FDA-approved treatment for these disorders is gene therapy for specific
RPE65 mutations that cause Leber’s congenital amaurosis and retinitis pigmentosa. One major
limitation to the development of effective therapies is the use of animal models that poorly replicate the
human condition. Particularly for cone disorders, studies that use animals with a rod-dominant retina
and no true macula have substantive limitations. By contrast, the cone-rich macula of nonhuman
primates (NHP) closely mirrors that of the human retina. Consequently, well-defined NHP models of
heritable retinal diseases, particularly cone disorders, that are more predictive of human conditions are
necessary to more efficiently advance new therapies. We propose to develop a series of novel and
spontaneous NHP models of human inherited retinal diseases. Behavioral observations of rhesus
macaques (Macaca mulatta) at the California National Primate Research Center identified a series of
macaques that displayed apparent visual impairment. Genetic testing showed that four animals are
homozygous for a damaging mutation in the PDE6C gene, which has previously been associated with
cone dystrophy in humans. Scotopic and photopic full-field electroretinograms performed on macaques
homozygous for the PDE6C mutation demonstrated a relatively normal rod response but no cone
response whatsoever. A subtle but characteristic bullseye maculopathy was identified using fundus
photography, blue autofluorescence, and fluorescein angiography with concurrent foveal thinning using
spectral-domain optical coherence tomography. Our genetic survey of this population also identified
macaques with mutations in 7 other human retinal disease genes that are predicted to severely damage
gene or protein function, pointing to possible additional new models. To develop the PDE6C primate
model of cone dystrophy, and make this and other new NHP models available to the vision research
community, we propose four Specific Aims: 1) to identify and genetically characterize new NHP models
of human retinal disease via DNA sequencing, 2) to perform complete ophthalmic phenotyping of NHP
models of retinal disease, 3) to breed a colony of NHPs with PDE6C cone dystrophy and 4) to compare
cell-based and gene replacement therapies in macaques with PDE6C cone dystrophy mutations.
Successful completion of this work will produce a well-characterized new animal model of inherited
cone dystrophy with significantly greater similarity to human disease than existing models, thus
providing substantially better translation to subsequent human trials. In addition, affected animals will
be made available to the wider vision research community, and other new models with similar potential
will be identified.

## Key facts

- **NIH application ID:** 10439118
- **Project number:** 3U24EY029904-04S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** JEFFREY A. ROGERS
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $150,000
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439118

## Citation

> US National Institutes of Health, RePORTER application 10439118, Novel model systems for the study of cone disorders and other heritable retinal diseases (3U24EY029904-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10439118. Licensed CC0.

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