Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein

Martin-Paul Agbaga; Md Nawajes A. Mandal; Robert E. Anderson

doi:10.1194/jlr.R005025

Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein

^*Departments of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
^†Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
^§Dean A. McGee Eye Institute, Oklahoma City, OK 73104

1To whom correspondence should be addressed. e-mail: robert-anderson{at}ouhsc.edu

Abstract

Compared with other mammalian tissues, retina is highly enriched in PUFA. Long-chain PUFA (LC-PUFA; C18-C24) are essential FAs that are enriched in the retina and are necessary for maintenance of normal retinal development and function. The retina, brain, and sperm also contain very LC-PUFA (VLC-PUFA; >C24). Although VLC-PUFA were discovered more than two decades ago, very little is known about their biosynthesis and functional roles in the retina. This is due mainly to intrinsic difficulties associated with working on these unusually long polyunsaturated hydrocarbon chains and their existence in small amounts. Recent studies on the FA elongase elongation of very long chain fatty acids-4 (ELOVL4) protein, however, suggest that VLC-PUFA probably play some uniquely important roles in the retina as well as the other tissues. Mutations in the ELOVL4 gene are found in patients with autosomal dominant Stargardt disease. Here, we review the recent literature on VLC-PUFA with special emphasis on the elongases responsible for their synthesis. We focus on a novel elongase, ELOVL4, involved in the synthesis of VLC-PUFA, and the importance of these FAs in maintaining the structural and functional integrity of retinal photoreceptors.

Footnotes

Abbreviations:

AOX

acyl-CoA oxidase

DHA or 22:6n3

docosahexaenoic acid

ELOVL

elongation of very long-chain FA

ELOVL4

elongation of very long-chain FA-4

ERG

electroretinogram

LC-PUFA

long-chain PUFA

PC

phosphatidylcholine

ROS

retinal outer segments

RPE

retinal pigment epithelium

STGD1

recessive Stargardt degeneration

STGD3

autosomal dominant Stargardt-like macular dystrophy

VLC-FA

very long-chain saturated or monounsaturated FA

VLC-PUFA

very long-chain PUFA
This work was supported by the following National Institutes of Health Grants: EY00871, EY04149, EY12190, and RR17703; and by the Foundation for Fighting Blindness, Research to Prevent Blindness, and Hope for Vision. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies.