Article

Retinitis pigmentosa. Lancet

Harvard University, Cambridge, Massachusetts, United States
The Lancet (Impact Factor: 45.22). 12/2006; 368(9549):1795-809. DOI: 10.1016/S0140-6736(06)69740-7
Source: PubMed

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.

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    • "In fact in STGD vitamin A cannot be properly metabolized because of ABCA4 protein impairment and gives origin to toxic byproducts which are the main components of lipofuscin[2,6]. On the other side in most RP patients genetic abnormalities prevent the appropriate processing of vitamin A in phototransduction and visual cycle[2,4,5,16]. Indeed, in opposite ways, both STGD and RP may be significantly influenced by dietary intake of these nutrients. "
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    ABSTRACT: Stargardt’s disease (STGD) and Retinitis Pigmentosa (RP) are inherited retinal degenerations that may be affected, in opposite way, by diet. Dietary profile was assessed in 24 patients with STGD and in 56 patients with RP. We documented in only 6 out of 24 (25 %) STGD patients a daily intake of vitamin A within the recommended range while 14/24 (58.3 %) reported a high daily intake and 4/24 (16.7 %) showed a low daily intake. With regard to RP, 4/56 (7.1 %) reported to be within the recommended range, 37/56 (66.1 %) reported high daily intake and 15/56 (26.8 %) showed low daily intake of vitamin A. Interestingly, STGD patients with low vitamin A intake (<600 µg RAE/day) showed significantly better visual acuity with respect to those introducing higher intake of vitamin A. The present study suggests insuitable nutrient intakes among patients with STGD and RP, especially for daily intake of vitamin A. The results may be used to provide tailored nutritional interventions in these patients.
    Full-text · Article · Dec 2016 · BMC Ophthalmology
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    • "In fact in STGD vitamin A cannot be properly metabolized because of ABCA4 protein impairment and gives origin to toxic byproducts which are the main components of lipofuscin[2,6]. On the other side in most RP patients genetic abnormalities prevent the appropriate processing of vitamin A in phototransduction and visual cycle[2,4,5,16]. Indeed, in opposite ways, both STGD and RP may be significantly influenced by dietary intake of these nutrients. "
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    ABSTRACT: Background: Stargardt’s disease (STGD) and Retinitis Pigmentosa (RP) are inherited retinal degenerations that may be affected, in opposite way, by diet. Methods: Dietary profile was assessed in 24 patients with STGD and in 56 patients with RP. We documented in only 6 out of 24 (25 %) STGD patients a daily intake of vitamin A within the recommended range while 14/24 (58.3 %) reported a high daily intake and 4/24 (16.7 %) showed a low daily intake. With regard to RP, 4/56 (7.1 %) reported to be within the recommended range, 37/56 (66.1 %) reported high daily intake and 15/56 (26.8 %) showed low daily intake of vitamin A. Results: Interestingly, STGD patients with low vitamin A intake (<600 μg RAE/day) showed significantly better visual acuity with respect to those introducing higher intake of vitamin A. Conclusion: The present study suggests insuitable nutrient intakes among patients with STGD and RP, especially for daily intake of vitamin A. The results may be used to provide tailored nutritional interventions in these patients.
    Full-text · Article · Jan 2016 · BMC Ophthalmology
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    • "Despite these advances in diagnosis and clinical characterization, molecular characterization of RP remains challenging due to the diversity of causal genes and their numerous disease-associated mutations. These disease genes are involved in a variety of processes both within and outside of the visual cycle, such as vitamin A metabolism, cell–cell interactions, cell structure, and signaling (reviewed in Hartong et al., 2006 ). "
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    ABSTRACT: Retinitis pigmentosa (RP) comprises several heritable diseases that involve photoreceptor, and ultimately retinal, degeneration. Currently, mutations in over 50 genes have known links to RP. Despite advances in clinical characterization, molecular characterization of RP remains challenging due to the heterogeneous nature of causal genes, mutations, and clinical phenotypes. In this study, we compiled large datasets of two important visual genes associated with RP: rhodopsin, which initiates the phototransduction cascade, and the retinoid isomerase RPE65, which regenerates the visual cycle. We used a comparative evolutionary approach to investigate the relationship between interspecific sequence variation and pathogenic mutations that lead to degenerative retinal disease. Using codon-based likelihood methods, we estimated evolutionary rates ( d N / d S ) across both genes in a phylogenetic context to investigate differences between pathogenic and nonpathogenic amino acid sites. In both genes, disease-associated sites showed significantly lower evolutionary rates compared to nondisease sites, and were more likely to occur in functionally critical areas of the proteins. The nature of the dataset (e.g., vertebrate or mammalian sequences), as well as selection of pathogenic sites, affected the differences observed between pathogenic and nonpathogenic sites. Our results illustrate that these methods can serve as an intermediate step in understanding protein structure and function in a clinical context, particularly in predicting the relative pathogenicity (i.e., functional impact) of point mutations and their downstream phenotypic effects. Extensions of this approach may also contribute to current methods for predicting the deleterious effects of candidate mutations and to the identification of protein regions under strong constraint where we expect pathogenic mutations to occur.
    Full-text · Article · Jan 2016 · Visual Neuroscience
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