# Physiological Role of the Vitamin A Transporter RBPR2 for Vision

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $75,533

## Abstract

PROJECT SUMMARY/ ABSTRACT
Distribution of dietary vitamin A/all-trans retinol/ROL throughout the body is critical to maintain retinoid
function in peripheral tissues and to ensure optimal vision. In humans, dietary ROL is absorbed in the intestine,
stored in the liver, and secreted into the circulation bound to serum retinol binding protein 4 (RBP4). The
circulatory dietary ROL bound RBP4 transport system has been suggested to specifically function in the ocular
vitamin A-dependent processes of vision in humans. Thus, an understanding of mechanisms that facilitate and
regulate the systemic uptake and transport of dietary vitamin A for ocular retinoid homeostasis are significant, to
help design strategies aimed at attenuating retinal degenerative diseases associated with serum ROL deficiency
or excess. The objectives of this proposal are to determine the physiological role a novel vitamin A transporter,
the retinol binding protein 4 receptor 2 (RBPR2), in facilitating the systemic uptake of dietary RBP4-ROL for
vision, and to understand if modulation of such eye related vitamin A transporters could improve vision in patients
with Stargardt disease suffering from toxic accumulation of vitamin A metabolites. The long-term goal is to
identify the mechanisms of RBPR2 for RBP4 binding and ROL transport in retinal health and disease. The central
hypothesis is that RBPR2 has high affinity binding for RBP4-ROL in tissues devoid of STRA6 and that its
physiological function is critical to ensure adequate dietary vitamin A uptake and delivery to the eye in the
continuous support of vision. The rationale underlying this proposal is that completion will fill the knowledge
gap of how dietary vitamin A is sequestered into systemic tissues from RBP4, transported and stored in peripheral
tissues lacking STRA6, for eventual distribution to the eye in the continuous support of vision. The central
hypothesis will be tested by pursuing three specific aims that will in: Aim 1] Determine the functionality of
RBPR2 for RBP4 binding and vitamin A/ROL uptake, Aim 2] Determine the physiological role of RBPR2 for
systemic RBP4-ROL transport for vision, and Aim 3] Determine if modulation of Rbpr2 activity attenuates retinal
degenerative diseases. We will pursue these aims using an innovative combination of structural analysis,
biochemistry, cell biology, physiology and generation of novel animal models aimed at exploring the in vivo
requirements of RBPR2 for ROL transport for photoreceptor health, vision and in attenuating retinal disease
states. The proposed research is significant, because it will determine for the first time the mechanisms facilitating
circulatory RBP4-ROL uptake, storage and transport into the eye, and explore whether modulation of such eye
related vitamin A transporters could improve vision in humans with inherited retinal degenerative diseases. The
proximate outcome of the proposed research will provide information that will improve understanding of hum...

## Key facts

- **NIH application ID:** 10551503
- **Project number:** 3R01EY030889-03S1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Glenn P Lobo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $75,533
- **Award type:** 3
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10551503

## Citation

> US National Institutes of Health, RePORTER application 10551503, Physiological Role of the Vitamin A Transporter RBPR2 for Vision (3R01EY030889-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10551503. Licensed CC0.

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