Lipid Peroxide Damage to the Retina of Albino Rabbits

Abstract

Lipid hydroperoxides (LHP) were synthesized from linoleic acid and injected into the eyes of albino rabbits. This produced a decline in electroretinographic (ERG) activity, a corresponding loss of key molecules localized in the photoreceptor outer segments, and formation of new compounds related to oxidative damage. During the first 2 days of the experimental period, a rapid and irreversible drop in protein, phospholipid, total polyunsaturated fatty acids, vitamin A, and α-tocopherol was observed. This change was so complete that retinal tissue lacked sufficient substrate to undergo any further oxidative stress. Following this initial event, there was an increase in the level of a compound with properties similar to those of the injected LHP, which suggests a propagation phenomena. Corresponding increases in other products of LHP metabolism and formation of conjugated fluorescent pigments also occurred. In response to the oxidative insult, antioxidant enzymes such as peroxidase and glutathione-S-transferase and lysosomal enzymes in general showed changes, but at different time intervals. Thus, an early rise at 2 days post-injection was seen in peroxidase, whereas the rise in transferase activity occurred at 14 days and remained elevated. Lysosomal enzymes rose sharply at 2 days and stayed above baseline levels over the following 2-week period. The present study has demonstrated the LHP are capable of producing severe damage to the retina and are the cause of decreased ERG activity in this type of degeneration.