ABSTRACT Hereditary degenerations of the human retina are genetically heterogeneous, with well over 100 genes implicated so far. This Seminar focuses on the subset of diseases called retinitis pigmentosa, in which patients typically lose night vision in adolescence, side vision in young adulthood, and central vision in later life because of progressive loss of rod and cone photoreceptor cells. Measures of retinal function, such as the electroretinogram, show that photoreceptor function is diminished generally many years before symptomic night blindness, visual-field scotomas, or decreased visual acuity arise. More than 45 genes for retinitis pigmentosa have been identified. These genes account for only about 60% of all patients; the remainder have defects in as yet unidentified genes. Findings of controlled trials indicate that nutritional interventions, including vitamin A palmitate and omega-3-rich fish, slow progression of disease in many patients. Imminent treatments for retinitis pigmentosa are greatly anticipated, especially for genetically defined subsets of patients, because of newly identified genes, growing knowledge of affected biochemical pathways, and development of animal models.
SourceAvailable from: Pietro Farinelli[Show abstract] [Hide abstract]
ABSTRACT: Defects in FAM161A, a protein of unknown function localized at the cilium of retinal photoreceptor cells, cause retinitis pigmentosa, a form of hereditary blindness. By using different fragments of this protein as baits to screen cDNA libraries of human and bovine retinas, we defined a yeast two-hybrid-based FAM161A interactome, identifying 53 bona fide partners. In addition to statistically significant enrichment in ciliary proteins, as expected, this interactome revealed substantial bias towards proteins from the Golgi apparatus, the centrosome, and the microtubule network. Validation of interaction with key partners by co-immunoprecipitation and proximity ligation assays confirmed that FAM161A is a member of the recently-recognized Golgi-centrosomal interactome, a network of proteins interconnecting Golgi maintenance, intracellular transport, and centrosome organization. Notable FAM161A interactors included AKAP9, FIP3, GOLGA3, KIFC3, KLC2, PDE4DIP, NIN, and TRIP11. Furthermore, analysis of FAM161A localization during the cell cycle revealed that this protein followed the centrosome during all stages of mitosis, likely reflecting a specific compartmentalization related to its role at the ciliary basal body during the G0 phase. Altogether, these findings suggest that FAM161A's activities are probably not limited to ciliary tasks but also extend to more general cellular functions, highlighting possible novel mechanisms for the molecular pathology of retinal disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com.Human Molecular Genetics 03/2015; DOI:10.1093/hmg/ddv085 · 6.68 Impact Factor
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ABSTRACT: To assess the psychological impact and the potential relationship between depression and visual impairment in patients with retinitis pigmentosa (RP). Our study included 34 patients with RP and 35 age- and sex-matched controls. All participants underwent a thorough ophthalmic examination including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, and dilated funduscopy, and they completed the Zung Depression Inventory questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Questionnaires were rated according to specific guidelines. Statistical analysis was performed using SPSS 20.0 software. There was a statistically significant difference in PHQ-9 score and Zung score between patients with RP and controls. The BCVA differed significantly between the 2 groups as well. Older subjects presented significantly higher Zung score and PHQ-9 score, as well as worse BCVA in both eyes. Sex did not show any significant correlation as far as Zung score, PHQ-9 score, or BCVA. Zung score was correlated positively with PHQ-9 score, while both Zung and PHQ-9 score were positively correlated with BCVA. Patients with RP seem to present mild to moderate depressive symptoms in comparison with healthy control subjects without visual impairment. These symptoms were found to be correlated with BCVA and age, suggesting that visual loss and older age in patients with RP could be predictive factors of their emotional status. Therefore, there is need for close monitoring and supportive management of this population, so as to detect depression and to treat it promptly.European journal of ophthalmology 03/2015; DOI:10.5301/ejo.5000590 · 1.06 Impact Factor
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ABSTRACT: Retinitis pigmentosa (RP), a heterogeneous group of inherited ocular diseases, is a genetic condition that causes retinal degeneration and eventual vision loss. Though some genes have been identified to be associated with RP, still a large part of the clinical cases could not be explained. Here we reported a four-generation Chinese family with RP, during which 6 from 9 members of the second generation affected the disease. To identify the genetic defect in this family, whole-exome sequencing together with validation analysis by Sanger sequencing were performed to find possible pathogenic mutations. After a pipeline of database filtering, including public databases and in-house databases, a novel missense mutation, c. 424 C > T transition (p.R142W) in OR2W3 gene, was identified as a potentially causative mutation for autosomal dominant RP. The mutation co-segregated with the disease phenotype over four generations. This mutation was validated in another independent three-generation family. RT-PCR analysis also identified that OR2W3 gene was expressed in HESC-RPE cell line. The results will not only enhance our current understanding of the genetic basis of RP, but also provide helpful clues for designing future studies to further investigate genetic factors for familial RP.Scientific Reports 03/2015; 5:9236. DOI:10.1038/srep09236 · 5.08 Impact Factor