The disk membranes of retinal photoreceptor outer segments and other neuronal and reproductive tissues are enriched in docosahexaenoic acid (DHA, 22:6n3), which is essential for their normal function ...and development. The fatty acid condensing enzyme Elongation of Very Long chain fatty acids-4 (ELOVL4) is highly expressed in retina photoreceptors as well as other tissues with high 22:6n3 content. Mutations in the ELOVL4 gene are associated with autosomal dominant Stargardt-like macular dystrophy (STGD3) and results in synthesis of a truncated protein that cannot be targeted to the endoplasmic reticulum (ER), the site of fatty acid biosynthesis. Considering the abundance and essential roles of 22:6n3 in ELOVL4-expressing tissues (except the skin), it was proposed that the ELOVL4 protein may be involved in 22:6n3 biosynthesis. We tested the hypothesis that the ELOVL4 protein is involved in 22:6n3 biosynthesis by selectively silencing expression of the protein in the cone photoreceptors derived cell line 661 w and showed that the ELOVL4 protein is not involved in DHA biosynthesis from the short chain fatty acid precursors 18:3n3 and 22:5n3.
Ceramide Signaling in Retinal Degeneration Chen, Hui; Tran, Julie-Thu A.; Brush, Richard S. ...
Advances in Experimental Medicine and Biology,
2012, Letnik:
723
Book Chapter, Journal Article
Recenzirano
Odprti dostop
Retinal degenerations (RD) are a complex heterogeneous group of diseases in which retinal photoreceptors and the supporting retinal pigment epithelial cells die irreversibly, causing visual loss for ...millions of people. Mutations on more than 150 genes have been discovered for RD and there are many forms that possess complex etiology involving more than one gene and environmental effect. For years, many have searched for some common intracellular second messenger for these many forms of cell death which could be targeted for therapy. Ceramide is a novel cellular second messenger which signals for apoptosis. Several lines of evidence suggest an integral role of ceramide in photoreceptor apoptosis and cell death. Understanding their role in the pathogenic pathways of retinal degenerative diseases is important for development of targeted therapeutics.
Retinal Degenerative Diseases Anderson, Robert E; Hollyfield, Joe G; LaVail, Matthew M
2010, 2009-12-01, Letnik:
664
eBook
This is the proceedings of the XIIIth International Symposium on Retinal Degenerations, held in Emeishan, Sichuan, China in September 2008. The themes include 'Molecular and genetic mechanisms in ...photoreceptor degeneration', 'New diagnostic techniques for retinal degenerations', and 'Age-related macular degeneration'.
Posterior polymorphous corneal dystrophy (PPCD, also known as PPMD) is a rare disease involving metaplasia and overgrowth of corneal endothelial cells. In patients with PPCD, these cells manifest in ...an epithelial morphology and gene expression pattern, produce an aberrant basement membrane, and, sometimes, spread over the iris and nearby structures in a way that increases the risk for glaucoma. We previously mapped PPCD to a region (PPCD3) on chromosome 10 containing the gene that encodes the two-handed zinc-finger homeodomain transcription factor TCF8. Here, we report a heterozygous frameshift mutation in TCF8 that segregates with PPCD in the family used to map PPCD3 and four different heterozygous nonsense and frameshift mutations in TCF8 in four other PPCD probands. Family reports of inguinal hernia, hydrocele, and possible bone anomalies in affected individuals suggest that individuals with TCF8 mutations should be examined for nonocular anomalies. We detect transcripts of all three identified PPCD genes (VSX1, COL8A2, and TCF8) in the cornea. We show presence of a complex (core plus secondary) binding site for TCF8 in the promoter of Alport syndrome gene COL4A3, which encodes collagen type IV α3, and we present immunohistochemical evidence of ectopic expression of COL4A3 in corneal endothelium of the proband of the original PPCD3 family. Identification of TCF8 as the PPCD3 gene provides a valuable tool for the study of critical gene regulation events in PPCD pathology and suggests a possible role for TCF8 mutations in altered structure and function of cells lining body cavities other than the anterior chamber of the eye. Thus, this study has identified TCF8 as the gene responsible for approximately half of the cases of PPCD, has implicated TCF8 mutations in developmental abnormalities outside the eye, and has presented the TCF8 regulatory target, COL4A3, as a key, shared molecular component of two different diseases, PPCD and Alport syndrome.
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