# Choroidal Gamma Delta T Cells as Novel Regulators of RPE Degeneration

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $420,499

## Abstract

PROJECT SUMMARY
Degeneration of the retinal pigment epithelium (RPE) is a pathological event commonly seen in various retinal
diseases such as age-related macular degeneration and retinitis pigmentosa. The RPE is part of the outer
blood retinal barrier that separates choroidal blood supply from the neurosensory retina. RPE injury activates
retinal and choroidal compartment immune cells. The responses can either promote repair and recovery of the
epithelium, or cause further tissue damage and immune pathology. Mechanisms controlling inflammation and
immune functions in the outer retina and choroid are largely unclear. Clarifying the interactions between the
RPE and immune cells is crucial for a better understanding of disease development and progression.  T
cells are a group of unconventional, innate-like lymphocytes with potent effects on cell-mediated immunity near
the epithelial barrier. We found that choroidal  T cells have novel protective functions in response to RPE
injury through their functional interactions with the RPE.  T cell-deficient mice show increased sensitivity to
sodium iodate-induced RPE damage and retinal toxicity; adoptive transfer of  T cells reverses this
sensitization. Immune regulatory cytokines, such as interleukins 4, 10 and 17, are produced by choroidal  T
cells via aryl hydrocarbon receptor (AhR)-dependent mechanisms. Accordingly, adoptive transfer of AhR-
deficient  T cells is not protective against RPE injury in the sodium iodate model. Based on the findings from
our published and preliminary studies, in the current proposal we hypothesize that choroidal  T
lymphocytes regulate tissue homeostasis in the outer retina via AhR-dependent mechanisms. Three
specific aims will be used to test the hypothesis. Aim 1 is to characterize choroidal  T cell function during
chronic RPE degeneration conditions. Aim 2 is to determine the mechanistic role of AhR in activation of
choroidal  T cells and their production of regulatory cytokines. Aim 3 is to determine whether modulating
AhR activity by dietary phytochemicals will influence the protective effects of choroidal  T cells against RPE
degeneration. The results from the proposed studies will define whether enhancing choroidal  T cell function
is potentially a novel interventional strategy for treating retinal diseases that involve RPE degeneration.

## Key facts

- **NIH application ID:** 10005361
- **Project number:** 5R01EY028773-03
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** JIYANG CAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,499
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005361

## Citation

> US National Institutes of Health, RePORTER application 10005361, Choroidal Gamma Delta T Cells as Novel Regulators of RPE Degeneration (5R01EY028773-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10005361. Licensed CC0.

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