Current Progress in Deciphering Importance of VLC-PUFA in the Retina

Abstract

Stargardt-like macular dystrophy-3 (STGD3) is a juvenile-onset disease caused by mutations in ELOVL4 (elongation of very long fatty acids-4). This gene product catalyzes the elongation of long chain saturated and polyunsaturated fatty acids (LC-FAs and LC-PUFAs) into very long chain FAs and PUFAs (VLC-FAs and VLC-PUFAs). These mutations cause a frame shift in the ELOVL4 transcript, introducing a premature stop codon that results in the translation of a truncated protein that has lost a C-terminus endoplasmic reticulum (ER) retention/retrieval signal. The truncated protein is not targeted to the ER, the site of very long-chain PUFA (VLC-PUFA; 28-40 carbons) synthesis. Expression of the ELOVL4 gene is limited mainly to the brain, testis, skin, and photoreceptor cells of the retina. While the skin and brain contain very long chain saturated fatty acids (VLC-FAs), the other tissues expressing ELOVL4 contain VLC-PUFAs, with sperm and the retina having the highest levels. This review focuses on the current information available concerning the role of VLC-PUFAs in the retina.

miRNAexpression profile of retinal pigment epithelial cells under oxidative stress conditions

“…However, because it is the only down‐expressed miRNA throughout all the time points, its role might be considered less decisive than the others. Therefore, a possible dysregulation of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling pathway emerged, a pathway already associated to retinal degeneration , along with fatty acid metabolism, known to be one of the most involved pathways in RP and its particular forms, such as Stargardt syndrome . Moreover, several new interesting pathways could be altered by the analyzed miRNAs, as emerged from target gene predictions.…”

Stargardt Phenotype Associated With Two ELOVL4 Promoter Variants and ELOVL4 Downregulation: New Possible Perspective to Etiopathogenesis?

“…ELOVL4 encodes a member of the elongase family, expressed in retina, brain, skin, and sperm, involved in the elongation of very long-chain fatty acids. 10 Although little is known about the role of this protein, data report that the contribution of the enzyme is to be found in the initial rate of VLC-PUFA production and condensation reactions between a fatty acyl-CoA and malonyl-CoA. 5 The role of VLC-PUFA is fundamental.…”

“…[5][6][7][8] ELOVL4 plays a fundamental role in the synthesis of very long-chain polyunsaturated fatty acids (VLC-PUFA). 9,10 VLC-PUFA make up a considerable part of phosphatidylcholine (PC) in the outer segment of both cell types of photoreceptors, suggesting a relevant role in the correct folding of disk rim and in cones and rods membrane fluidity. 11 These functions, together with a close interaction with rhodopsin, strongly point to the possible involvement of ELOVL4 in phototransduction.…”

Retinal Degeneration and Regeneration—Lessons From Fishes and Amphibians

“…The authors propose that rhodopsin mutations cause CNB as a result of persistent signaling by the constitutively active opsin [ 52 ]. Stargardt-like macular dystrophy is a juvenile macular degeneration caused by mutations in the elongation of very long-chain fatty acids 4 ( ELOVL4 ) gene [ 53 ]. A Xenopus transgenic model of this disease, overexpressing dominant negative ELOVL4 variants, has been generated [ 54 ].…”