# STRA6 and Ocular Vitamin A Homeostasis

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $473,430

## Abstract

ABSTRACT
The fat-soluble vitamin A (all-trans-retinol) is distributed in the body to maintain retinoid signaling
in peripheral tissues and vision in the eyes. This transport occurs via an extrinsic pathway for the
distribution of dietary vitamin A in the form of retinyl esters in chylomicrons and an intrinsic
pathway for the distribution of vitamin A from hepatic stores bound to the retinoid binding protein
RBP4. Cellular uptake of vitamin A from these two transport modes is facilitated by lipoprotein
lipase and by the RBP4 receptor STRA6 (Stimulated by Retinoic Acid 6), respectively. Disrupted
vitamin A transport is a serious health problem and is associated with blinding diseases ranging
from night blindness to complex ophthalmic syndromes. We propose to study the etiology of
ocular diseases states that are associated with perturbed ocular vitamin A uptake homeostasis
by comparing the eyes of STRA6-deficient and that of control mice.
In Aim 1, we will examine the role of STRA6 in the functioning of the outer blood-retinal barrier.
We will study whether ocular vitamin A deficiency in Stra6 knockout mice impairs the structural
integrity and functioning of this barrier. Additionally, we will examine whether retinoid signaling
regulates the expression of key components of both the outer blood-retina barrier in mice and
human retina pigment epithelium cells derived from inducible pluripotent stem cells. In Aim 2, we
will use Stra6 knockout mice to analyze the consequences of imbalances in ocular retinoid
concentrations on rod and cone photoreceptor function and ultrastructure. We will generate novel
transgenic mouse lines to examine the competition between rods and cones for limited
chromophore in the STRA6-deficient eyes. This research will address the question whether the
STRA6/RBP4-dependent transport system is an adaption to the high chromophore demand from
rod photoreceptors. In Aim 3, we will study whether manipulation of the extrinsic pathway can
rescue cone and rod photoreceptor function in STRA6-deficiency and whether the STRA6/RBP4
uptake system provides selectivity for the uptake of canonical retinoids. Collectively, our proposed
studies will advance knowledge about ocular vitamin A homeostasis by elucidating its
mechanisms in the physiological state and by studying the consequences of its loss-of-function
in disease states.

## Key facts

- **NIH application ID:** 10929474
- **Project number:** 5R01EY028121-07
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Johannes Friedrich von Lintig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $473,430
- **Award type:** 5
- **Project period:** 2018-08-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929474

## Citation

> US National Institutes of Health, RePORTER application 10929474, STRA6 and Ocular Vitamin A Homeostasis (5R01EY028121-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10929474. Licensed CC0.

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