Genetic inactivation of cellular retinol-binding protein 1 slows bis-retinoid accumulation, protecting against retinal degeneration in a mouse model of Stargardt disease.
Delayed clearance of all-trans-retinal (at-RAL) in photoreceptors is linked to prevalent retinal diseases such as Stargardt disease, rod-cone dystrophies, and age-related macular degeneration. Pharmacological modulation of retinoid metabolism in the eye presents a promising therapeutic strategy, with cellular retinol-binding protein 1 (RBP1) emerging as a potential target. However, it lacks genetic validation as a therapeutic target in an animal model of human disease. Thus, we investigated the effect of the Rbp1 gene inactivation on the phenotype of the Abca4-/-/Rdh8-/- model of Stargardt disease. Triple knockout (Abca4-/-/Rdh8-/-/Rbp1-/-) mice were protected against light-induced retinal degeneration. RBP1 deficiency also slowed bis-retinoid accumulation in aged animals. Furthermore, pharmacological inhibition of RBP1 alleviated the retinal degeneration phenotype. These findings provide both genetic and pharmacological evidence supporting RBP1 as a promising therapeutic target for retinal degenerative diseases associated with impaired at-RAL clearance.
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Widjaja‐Adhi et al. (2025) studied this question.
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