A hypothesis to explain the reduced blood levels of docosahexaenoic acid in inherited retinal degenerations caused by mutations in genes encoding retina-specific proteins.
Some humans and animals with inherited retinal degenerations (RD) have lower blood levels of docosahexaenoic acid (22:6n-3) than controls. As a result of recent studies, clearly the low blood 22:6n-3 phenotype is found in multiple RD phenotypes and no mutation thus far identified in humans or animals is involved in lipid metabolism. Therefore, it seems reasonable to suggest that the primary defect is not in 22:6n-3 metabolism, but rather in some common convergent pathway that ultimately leads to the reduction of blood and tissue 22:6n-3 levels. One possibility is that the different mutations produce a metabolic stress that provokes structural and biochemical adaptive changes in photoreceptor cells and their rod outer segments. If the stress is oxidant, the retina could downregulate 22:6n-3 and upregulate antioxidant defenses. How such a stress could lead to changes in blood levels of 22:6n-3 is not obvious. However, the consistent finding of the 22:6n-3 phenotype in many different retinal degeneration genotypes suggests that some form of communication exists between the retina and other tissues that serves to reduce blood levels of 22:6n-3.
Anderson
R E
RE
Department of Ophthalmology, Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA. robert-anderson@ouhsc.edu
Maude
M B
MB
Alvarez
R A
RA
Acland
G
G
Aguirre
G D
GD
D000818:Animals; D004281:Docosahexaenoic Acids / Q000097:blood*; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D012016:Reference Values; D012160:Retina / Q000378:metabolism*; D012162:Retinal Degeneration / Q000097:blood* / Q000235:genetics*; D012374:Rod Cell Outer Segment / Q000378:metabolism
D004281:Docosahexaenoic Acids