Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein

Area of Science:

• Biochemistry
• Molecular Biology
• Ophthalmology

Background:

• Retinol-binding protein (RBP) is the primary carrier of retinol (vitamin A) in circulation.
• Retinol is essential for vision and gene regulation, requiring activation to retinoic acid or 11-cis-retinal.
• The precise role of RBP in tissue delivery and vitamin A homeostasis remains incompletely understood.

Purpose of the Study:

• To investigate the function of RBP in retinol transport and vitamin A metabolism using a knockout mouse model.
• To determine the necessity of RBP for retinal function and vision development.
• To elucidate the role of RBP in maintaining vitamin A status under varying dietary conditions.

Main Methods:

• Generation of RBP knockout mice (RBP(-/-)) via gene targeting.
• Assessment of retinal function and vision in RBP(-/-) mice across different age groups.
• Analysis of blood retinol levels and hepatic retinol stores in RBP(-/-) mice under vitamin A-sufficient and deficient diets.

Main Results:

• RBP(-/-) mice exhibit reduced blood retinol and impaired retinal function in early life, which normalizes with age on a sufficient diet.
• Despite low blood retinol, RBP(-/-) mice achieve normal vision by 5 months on a vitamin A-sufficient diet.
• RBP(-/-) mice cannot mobilize hepatic retinol stores, leading to rapid vision deterioration and undetectable serum retinol upon dietary vitamin A deprivation.

Conclusions:

• RBP is essential for normal vision in young animals and for retinol mobilization during vitamin A deficiency.
• RBP plays a critical, yet dispensable, role in retinol delivery to tissues, particularly under conditions of insufficient dietary intake.
• The study highlights RBP's importance in maintaining vitamin A homeostasis and supporting visual function, especially in early life and during nutritional stress.