Lifelong
n–3 fatty acid deficiency also affected the relationship between blue-light exposure and lesion size, but unlike xanthophyll deficiency, the effect was seen, not in the fovea but in the parafovea (
Fig. 2D), a locus of particular susceptibility to age-related rod loss.
58 This protective effect of
n–3 fatty acids must be qualified as occurring on a background of life-long absence of xanthophylls, since our experiment did not include a group deficient in
n–3 fatty acids while having long-term normal xanthophyll levels. However, the effect was seen in both the xanthophyll-free and supplemented conditions. Unlike L and Z, DHA is a major structural component of outer segment membranes throughout the retina and appears to comprise a slightly higher proportion of total fatty acids in the peripheral retina than in the macula.
59 At first glance, our results appear inconsistent with those in previous studies of acute light-induced damage in
n–3 fatty acid–deficient rodents, which showed an opposite, protective effect of low DHA concentrations that was ascribed to the high vulnerability of DHA to oxidative damage.
43,44 However, these studies involved different light damage mechanisms, as they used diffuse light exposures at middle wavelengths designed to maximally activate rhodopsin.
60 Other evidence of potentially negative effects of
n–3 fatty acids comes from studies showing that oxidative products of DHA form protein adducts that are elevated in AMD patients' plasma and RPE.
61 On the other hand, several recent studies provide rationales for antioxidative, anti-inflammatory, and neuroprotective actions of DHA and its metabolites within the retina. For example, DHA is the precursor of neuroprotectin D1, a lipid mediator that promotes RPE cell survival by multiple mechanisms under conditions of oxidative stress (e.g., Ref.
62) and it also is the precursor of related anti-inflammatory compounds termed resolvins.
63 Furthermore, in cultures of retinal neurons and RPE cells, DHA or its derivatives block oxidative damage-induced apoptosis.
64,65 These considerations suggest that DHA probably has both positive and negative influences on neuronal sensitivity to light damage and that the final outcome depends on the balance among them, which could be dependent on the animal species and the type of light exposure.