The
fat-1 gene cloned from C. elegans encodes an
n3 fatty acid desaturase that converts
n6 to
n3 polyunsaturated fatty acids (PUFA). Mice carrying the
fat-1 transgene and wildtype controls were fed an
n3-deficient/n6-enriched diet (
fat-1-SFO and wt-SFO, respectively). Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver determined by gas-liquid chromatography demonstrated significantly lower
n6/n3 ratios and higher docosahexaenoic acid (DHA) levels in
fat-1-SFO compared to wt-SFO. When mice were exposed to light stress of 3000 lux for 24 h: (1) the outer nuclear layer thickness, a measure of the number of surviving photoreceptors, was reduced; (2) a- and b-wave amplitudes of the electroretinogram, measures of retinal function, were lower; and (3) the number of TUNEL positive photoreceptor cells was greater in wt-SFO compared to both
fat-1-SFO and wt mice fed a regular lab chow diet (wt-RD). With damaging light exposure, modification of retinal proteins by 4-hydroxyhexenal, an end-product of
n3 PUFA oxidation, was increased in
fat-1-SFO and wt-RD compared to wt-SFO and unexposed animals. However, modification of retinal proteins by 4-hydroxynonenal, an end-product of
n6 PUFA oxidation, was increased in all 3 light-exposed groups compared to unexposed animals. The results indicate a positive correlation between the level of DHA, the degree of
n3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. Sensitivity, a measure of the gain steps of phototransduction, as tested by a-wave analysis, was higher in
fat-1-SFO and wt-RD compared to wt-SFO, correlating with higher DHA levels measured in ROS. In mice not exposed to intense light, the reduction in DHA resulted in no differences in the retinal morphology or retinal biochemistry, as measured by Western blot analyses of phototransduction-related proteins and by rhodopsin measurements. These results highlight the dual roles of DHA in cellular physiology and pathology.