# STRA6 and Ocular Vitamin A Homeostasis

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $484,030

## Abstract

ABSTRACT
The fat soluble vitamin A (all-trans-retinol) must be distributed in the body to maintain retinoid
signaling in the periphery and vision in the eyes. This transport occurs via two overlapping
pathways: vitamin A from the diet is distributed in the form of retinyl esters in chylomicrons and
vitamin A from hepatic stores is distributed bound to the retinol binding protein RBP4 (holo-
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. Deficiency
of vitamin A transport is a serious health problem and associated with blinding diseases. We
have generated a STRA6-deficient mouse model. As demonstrated by our recent studies and
preliminary data, ocular retinoid concentrations can be manipulated in this mouse model in by
dietary intervention. Control mice can maintain their ocular retinoids under this condition. Thus,
this mouse model presents a unique animal model to study the biochemistry of vitamin A and
physiology of transport and the consequences of its pathological impairment in certain disease
states.
In Aim 1 we will analyze the role of the RBP4 receptor in leveling ocular vitamin A as a
bidirectional transporter in live animals. In Aim 2, we will use the Stra6 knockout mouse to
analyze the consequences of imbalances in ocular retinoid concentrations for ocular health. By
combining the knowledge of aberrant genetic pathways with imaging techniques and
biochemical analyses, we will connect the transcriptome to the phenotype of the eyes in the
vitamin A deficient and sufficient states. In Aim 3 we will study whether disturbances in ocular
vitamin A metabolism is a characteristic of the etiology of diabetic retinopathy and will test
whether reduced ocular vitamin A concentration can alleviate pathological consequences of this
disease in the mouse eyes. Collectively, our proposed studies will advance our current
knowledge about the biology of ocular vitamin A homeostasis. Our studies will describe the
molecular and biochemical framework through which ocular vitamin A homeostasis is
maintained in the physiological state and decipher the pathological consequences of perturbed
ocular vitamin A import and export in disease states.

## Key facts

- **NIH application ID:** 9982937
- **Project number:** 5R01EY028121-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Johannes Friedrich von Lintig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $484,030
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982937

## Citation

> US National Institutes of Health, RePORTER application 9982937, STRA6 and Ocular Vitamin A Homeostasis (5R01EY028121-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982937. Licensed CC0.

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