# Biosynthesis and trafficking of phosphodiesterase in the retinal photoreceptors

> **NIH NIH R01** · WEST VIRGINIA UNIVERSITY · 2022 · $376,329

## Abstract

PROJECT SUMMARY/ABSTRACT
The long term goals of our research are to study the role of post-translational protein modifications and their
role in phototransduction protein synthesis and maturation. The purpose of this proposal is to investigate the
importance of the isoprenylation of phosphodiesterase-6 (PDE6) in retinal photoreceptor neurons. PDE6 is
an enzyme that is essential for vision, and its absence or mutations in humans lead to retinitis pigmentosa
(RP) and color blindness. Interestingly, changes in Aryl hydrocarbon receptor protein-like-1 (AIPL1), a co-
chaperone for PDE6 leads to more severe childhood blindness. Despite the clear link to several blinding
diseases, our knowledge on assembly and maturation of this essential enzyme in photoreceptor neurons is
not known. Our study will specifically focus on the interplay between AIPL1, HSP90, and lipid modification in
PDE6 assembly, maturation, and trafficking to the photoreceptor outer segments. We will also study the
importance of differential isoprenylation in mediating light-dependent signaling in the photoreceptor cells.
We will use a combination of unique animal models, in vivo electrophysiological measurements, ex vivo
retinal culture models and in vitro biochemical analyses to comprehensively address this question.
Our proposed studies are aligned with the Retinal Diseases Program of the NEI to “Identify the genes
involved in both inherited and retinal degenerative diseases (including RP), determine the
pathophysiological mechanisms underlying these mutations, and determine new potential therapeutic
strategies for treatment such as gene transfer, tissue and cell transplantation, growth factor therapy, and
pharmacological intervention.” Our proposed studies have clinical implications, such as therapy for
mutations in PDE6 and AIPL1 that lead to blindness in humans.

## Key facts

- **NIH application ID:** 10376198
- **Project number:** 5R01EY031346-03
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Visvanathan Ramamurthy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $376,329
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376198

## Citation

> US National Institutes of Health, RePORTER application 10376198, Biosynthesis and trafficking of phosphodiesterase in the retinal photoreceptors (5R01EY031346-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10376198. Licensed CC0.

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