Rlbp1-flox Mouse

RLBP1, encoding cellular retinaldehyde-binding protein (CRALBP), is a crucial gene in the visual cycle. CRALBP is essential in rod and cone visual cycles, primarily located in the retinal pigment epithelium (RPE) and Müller cells of the neuroretina. By binding 11-cis-retinoid, it augments RPE65 isomerase activity, facilitates 11-cis-retinol oxidation to 11-cis-retinal, maintains the 11-cis configuration, and protects against unwanted retinaldehyde activity [2,3].

In an Rlbp1-/-murine model, reduced 11-cis-retinal levels, quantitative fundus autofluorescence (qAF), near-infrared autofluorescence (NIR-AF) intensities, and photoreceptor loss were observed, consistent with the clinical presentation of affected siblings in human studies of RLBP1-associated diseases. This indicates that RLBP1 mutations lead to progressive disease involving RPE atrophy and photoreceptor cell degeneration [3]. In a 5-year prospective study of patients with RLBP1-associated retinal dystrophy, severely delayed dark-adaptation (DA) sensitivity recovery was a characteristic feature, suggesting it could be a suitable efficacy assessment for gene therapy in this patient population [1]. Gene therapy using AAV8-RLBP1 in patients with RLBP1-associated retinal dystrophy showed preliminary safety and efficacy, with significant improvement in dark-adaptation kinetics and resolution of disease-related retinal deposits [4].

In conclusion, RLBP1 is vital for the normal function of the visual cycle. Studies using gene-knockout mouse models and human patient-based research have revealed its role in maintaining retinal health. Understanding RLBP1 function through these models is crucial for developing effective therapies for RLBP1-associated retinal dystrophies.