# Circadian regulation of RPE functions

> **NIH NIH R01** · MOREHOUSE SCHOOL OF MEDICINE · 2020 · $494,213

## Abstract

The retinal pigment epithelium (RPE) is involved in many processes necessary to
maintain photoreceptor function and health. The RPE is also involved in the regulation of
the photoreceptor outer segment turnover (disk shedding and phagocytosis) a process
that has been shown to be under circadian control. We have recently developed an
RPE-choroid preparation in which we can monitor, in real-time, the circadian clock using
the PER2::LUC knock-in mouse, a transgenic mouse model where the PER2 oscillation
is faithfully reported via a firefly luciferase. This model is unique in that it reflects both
transcription and post-translational events, providing a powerful tool to investigate
circadian clock function in a specific tissue and/or cell. Using this new preparation we
have demonstrated that the mouse RPE contains a circadian clock that is entrained by
the neuromodulator dopamine (DA). In the present proposal (Specific Aim 1) we will test
the hypothesis that DA, via D2-like receptors located in the RPE, entrains the circadian
clock in the RPE, thus synchronizing the daily burst in phagocytosis of rod outer
segment disks. Then we will identify the molecular mechanisms by which DA
synchronizes the circadian clock in the RPE. In Specific Aim 2 we will test the prediction
that removal of D2R signaling will affect the daily rhythm of phagocytosis thus leading to
lipofuscin accumulation and reduced photoreceptor viability during aging. Finally, in
Specific Aim 3 we will define the roles of RPE and inner retinal clocks in the regulation of
the daily rhythm in RPE phagocytic activity. To reach this goal we will disrupt circadian
clocks selectively in RPE and neural retina and assess the consequences on the daily
rhythm of phagocytosis. The experiments described in this research proposal will
determine the role that DA and its associated receptors play in the regulation of the
circadian rhythms in the RPE and the role of retinal/RPE circadian clocks in the
regulation of the daily rhythm of RPE phagocytic activity.

## Key facts

- **NIH application ID:** 9980411
- **Project number:** 5R01EY026291-05
- **Recipient organization:** MOREHOUSE SCHOOL OF MEDICINE
- **Principal Investigator:** Gianluca Tosini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $494,213
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980411

## Citation

> US National Institutes of Health, RePORTER application 9980411, Circadian regulation of RPE functions (5R01EY026291-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980411. Licensed CC0.

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