Large Benefit from Simple Things: High-Dose Vitamin A Improves RBP4-Related Retinal Dystrophy

Vasily M Smirnov (1) , Baptiste Wilmet (1) , Marco Nassisi (1) , Christel Condroyer (1) , Aline Antonio (1) , Camille Andrieu (2) , Céline Devisme (2) , Serge Sancho (2) , José-Alain Sahel (1, 2, 3) , Christina Zeitz (1) , Isabelle Audo (1, 2)

1 Institut de la Vision
2 CIC1423 - CIC QUINZE-VINGTS - Centre d'investigation clinique Quinze-Vingts [CHNO]
3 University of Pittsburgh School of Medicine

Inherited retinal diseases (IRD) are a group of heterogeneous disorders, most of which lead to blindness with limited therapeutic options. Pathogenic variants in RBP4, coding for a major blood carrier of retinol, retinol-binding protein 4, are responsible for a peculiar form of IRD. The aim of this study was to investigate if retinal function of an RBP4-related IRD patient can be improved by retinol administration. Our patient presented a peculiar white-dot retinopathy, reminiscent of vitamin A deficient retinopathy. Using a customized next generation sequencing (NGS) IRD panel we discovered a novel loss-of-function homozygous pathogenic variant in RBP4: c.255G >A, p.(Trp85*). Western blotting revealed the absence of RBP4 protein in the patient's serum. Blood retinol levels were undetectable. The patient was put on a high-dose oral retinol regimen (50,000 UI twice a week). Subjective symptoms and retinal function markedly and sustainably improved at 5-months and 1-year follow-up. Here we show that this novel IRD case can be treated by oral retinol administration.

Mots clés: inherited retinal degeneration; fundus albipunctatus; retinol-binding protein; RBP4; retinol treatment

Domaines: Organes des sens; Alimentation et Nutrition

Vasily M Smirnov, Baptiste Wilmet, Marco Nassisi, Christel Condroyer, Aline Antonio, et al.. Large Benefit from Simple Things: High-Dose Vitamin A Improves RBP4-Related Retinal Dystrophy. International Journal of Molecular Sciences, 2022, 23 (12), pp.6590. ⟨10.3390/ijms23126590⟩. ⟨hal-03954576⟩