Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder. And several gene loci and transporter proteins that associated with uric acid transport functions have been identified. Retinol Dehydrogenase 12 (RDH12), recognized for its role in safeguarding photoreceptors, and our study investigated the potential impact of Rdh12 mutations on other organs and diseases, particularly hyperuricemia. We assessed Rdh12 mRNA expression levels in various tissues and conducted serum biochemical analyses in Rdh12-/- mice. Compared with the wild type, significant alterations in serum uric acid levels and kidney-related biochemical indicators have been revealed. Then further analysis, including quantitative RT-PCR of gene expression in the liver and kidney, highlighted variations in the expression levels of specific genes linked to hyperuricemia. And renal histology assessment exposed mild pathological lesions in the kidneys of Rdh12-/- mice. In summary, our study suggests that Rdh12 mutations impact not only retinal function but also contribute to hyperuricemia and renal disease phenotypes in mice. Our finding implies that individuals with Rdh12 mutations may be prone to hyperuricemia and gout, emphasizing the significance of preventive measures and regular examinations in daily life.

To study the associations between RDH12 gene mutations, fundus types, and clinical manifestations. In total, 46 patients with inherited eye diseases caused by RDH12 gene mutations were included in this study. High-throughput chip capture sequencing, Sanger sequencing, and gene panel detection were used to determine that RDH12 was the pathogenic gene. All patients underwent the following detailed ophthalmic examinations: visual acuity, visual field, intraocular pressure, fundus photography, electroretinography, and optical coherence tomography (OCT). Statistical analysis was used to evaluate the clinical phenotype. A total of 32 mutations were identified in 46 patients. The most common mutations were c.437T > A, c.184C > T, and c.524C > T; the corresponding amino acid changes were p.Val146Asp, p.Arg62Ter, and p.Ser175Leu. Of the 46 patients, retinitis pigmentosa (RP) was found in 31 (68.9%); leber congenital amaurosis (LVA) was found in 11 (24.4%); early onset of severe retinal dystrophy (EOSRD) was found in one (2.2%); cone rod dystrophy (CORD) was found in one (2.2%); and Stargardt disease was found in one (2.2%). There was a significant difference in best-corrected visual acuity among patients based on fundus type (p = 0.0124). Linear trend analysis showed that best-corrected visual acuity gradually decreased as the fundus type increased in severity. In addition, there was a significant difference in the incidence of night blindness among patients with different fundus types (p = 0.0429): types I and IV fundi were associated with the highest incidences of night blindness. RDH12 gene mutation can cause serious inherited retinal diseases, which primarily include RP and LCA. Combined with clinical symptoms and fundus types, the progression of the disease can be characterized and used to guide genetic diagnosis and gene therapy.

UNASSIGNED: The aim of study was to establish Rdh12-associated inherited retinal disease (Rdh12-IRD) mouse model and to identify the best timepoint for gene therapy.
UNASSIGNED: We induced retinal degeneration in Rdh12-/- mice using a bright light. We clarified the establishment of Rdh12-IRD mouse model by analyzing the thickness of retinal layers and electroretinography (ERG). Rdh12-IRD mice received a subretinal injection of adeno-associated virus 2/8-packaged Rdh12 cDNA for treatment. We evaluated the visual function and retinal structure in the treated and untreated eyes to identify the best timepoint for gene therapy.
UNASSIGNED: Rdh12-IRD mice showed significant differences in ERG amplitudes and photoreceptor survival compared to Rdh12+/+ mice. Preventive gene therapy not only maintained normal visual function but also prevented photoreceptor loss. Salvage gene therapy could not reverse the retinal degeneration phenotype of Rdh12-IRD mice, but it could slow down the loss of visual function.
UNASSIGNED: The light-induced retinal degeneration in our Rdh12-/- mice indicated that a defect in Rdh12 alone was sufficient to cause visual dysfunction and photoreceptor degeneration, which reproduced the phenotypes observed in RDH12-IRD patients. This model is suitable for gene therapy studies. Early treatment of the primary Rdh12 defect helps to delay the later onset of photoreceptor degeneration and maintains visual function in Rdh12-IRD mice.

Background: Leber congenital amaurosis (LCA) due to RDH12 mutations typically manifests with severe vision loss and panretinal dystrophy. We sought to describe a case of LCA with choroidal neovascularization (CNV) in a 17-year-old patient. Materials and Methods: Case report of a 17-year old with LCA who presented with acute central vision loss of the right eye in the context of a chronic retinal dystrophy. Multimodal retinal imaging including spectral-domain optical coherence tomography and indocyanine green angiography revealed CNV. Results: A 17-year-old boy with previously diagnosed LCA/early-onset retinal dystrophy (EOSRD), with subsequently identified biallelic mutations in RDH12 was found to have type 2 CNV. Patient was treated with intravitreal ranibizumab and exhibited improvement on follow-up exam. Conclusions: Choroidal neovascularization may be a unique occurrence in RDH12-associated retinal dystrophy. Successful treatment of the neovascularization could be accomplished with intravitreal antivasogenic therapy.