Docosapentaenoic acid is converted to docosahexaenoic acid in the retinas of normal and prcd-affected miniature poodle dogs.
OBJECTIVE
Docosahexaenoic acid (DHA, 22:6n-3) is the major fatty acid of photoreceptor membranes that is necessary for optimal retinal function. Miniature poodle dogs with progressive rod-cone degeneration have lower plasma levels of DHA than normal dogs and higher 22:5n-3/22:6n-3 ratios. The purpose of this study was to test the hypothesis that the metabolic defect in dogs affected with progressive rod-cone degeneration was a reduced capacity for ocular synthesis of DHA from its precursor 22:5n-3.


METHODS
The in vivo retinal conversion of [14C]22:5n-3 to [14C]22:6n-3 was investigated by injecting normal dogs and dogs affected with progressive rod-cone degeneration intravitreally with [14C]22:5n-3. After 72 hours, rod outer segments, remaining retina, and retinal pigment epithelium/choroid were analyzed for metabolic products.


RESULTS
Using high-performance liquid chromatography, six radioactive peaks were detected in both normal and affected dogs: [14C]20:5n-3, [14C]22:6n-3, [14C]22:5n-3, [14C]24:6n-3, [14C]24:5n-3, and [14C]18:0. The majority of the label in each tissue was in 22:6n-3 and there was no difference in the dpm% of [14C]22:6n-3 in normal and affected animals in any of the three tissues. Voss et al (J Biol Chem 1991;266:19995-20000) proposed a new pathway for the synthesis of DHA that involves elongation of 22:5n-3 to 24:5n-3, desaturation to 24:6n-3, and beta-oxidation to 22:6n-3. Identification of the products [14C]24:5n-3 and [14C]24:6n-3 verified that these putative intermediates are present in the dog retina.


CONCLUSIONS
The finding of large amounts of label in DHA shows that the normal and progressive rod-cone-degenerated retina and retinal pigment epithelium are capable of DHA synthesis from 22:5n-3. The presence of radioactivity in 24:5n-3 and 24:6n-3 suggests that the synthesis of DHA in the retina is similar to that described in the liver.
Alvarez
R A
RA
Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030.
Aguirre
G D
GD
Acland
G M
GM
Anderson
R E
RE
D000818:Animals; D004281:Docosahexaenoic Acids / Q000302:isolation & purification / Q000378:metabolism*; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*
D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; C026219:docosapentaenoic acid