Inherited retinal diseases (IRDs) represent a genetically and clinically heterogenous group of diseases that can eventually lead to blindness. Advances in sequencing technologies have resulted in better molecular characterization and genotype-phenotype correlation of IRDs. This has fueled research into therapeutic development over the recent years. Animal models are required for pre-clinical efficacy assessment. Non-human primates (NHP) are ideal due to the anatomical and genetic similarities shared with humans. However, developing NHP disease to recapitulate the disease phenotype for specific IRDs may be challenging from both technical and cost perspectives. This review discusses the currently available NHP IRD models and the methods used for development, with a particular focus on gene-editing technologies.
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http://dx.doi.org/10.3390/genes13020344 | DOI Listing |
Klin Monbl Augenheilkd
January 2025
Department of Ophthalmology (Chairman Prof. Valmaggia), Cantonal Hospital St. Gallen, Switzerland.
Purpose: Color vision deficiency (CVD) is a common vision disorder. It is predominantly caused by inherited photopigment abnormalities in the retina. The absolute number of cases with CVD is expected to increase worldwide with the growing population.
View Article and Find Full Text PDFD e h ydro d olichyl d iphosphate s ynthase (DHDDS) is an essential enzyme required for several forms of protein glycosylation in all eukaryotic cells. Surprisingly, three mutant alleles, ( (K42E/K42E), (T206A/K42E), and found in only one patient, (R98W/K42E) have been reported that cause non-syndromic retinitis pigmentosa (RP59), an inherited retinal degeneration (IRD). Because T206A was only observed heterozygously with the K42E allele in RP59 patients, we used CRISPR/CAS9 technology to generate T206A/T206A, and subsequently T206A/K42E alleles in mice to assess the contribution of the T206A allele to the disease phenotype, to model the human disease, and to compare resulting phenotypes to our homozygous K42E mouse model.
View Article and Find Full Text PDFOphthalmic Genet
January 2025
Department of Ophthalmology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
Introduction: Optic disc drusen (ODD) are believed to have a genetic predisposition, with autosomal dominant inheritance pattern with incomplete penetrance suggested through family pedigree analysis. ODD prevalence is higher in certain genetic disorders, such as pseudoxanthoma elasticum and retinitis pigmentosa. This study aimed to identify candidate genes potentially involved in the development of ODD.
View Article and Find Full Text PDFClin Genet
January 2025
Department of Medical Genetics, Medical Faculty, Aksaray University, Aksaray, Turkiye.
Inherited retinal diseases (IRDs) constitute a heterogeneous group of clinically and genetically diverse conditions, standing as a primary cause of visual impairment among individuals aged 15-45, with an estimated incidence of 1:2000. Our study aimed to comprehensively evaluate the genetic variants underlying IRDs in the Turkish population. This study included 50 unrelated Turkish IRD patients and their families.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, NE 68178, USA.
Inherited retinal disorders (IRDs) represent a group of challenging genetic conditions that often lead to severe visual impairment or blindness. The complexity of these disorders, arising from their diverse genetic causes and the unique structural and functional aspects of retinal cells, has made developing effective treatments particularly challenging. Recent advancements in gene therapy, especially non-viral nucleic acid delivery systems like liposomes, solid lipid nanoparticles, dendrimers, and polymersomes, offer promising solutions.
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