Lipoxygenase metabolism following laser induced retinal injury in rabbits

1) to investigate whether leukotriene B(4) (LTB(4)) is a factor in the inflammatory reaction following chorioretinal laser injury in rabbits; 2) to study its relationship with the cyclooxygenase (COX) metabolic pathway; 3) to study the influence of Nordihydroguaiaretic acid (NDGA), an inhibitor; of the lipoxygenase (LOX) cascade, on both COX and LOX metabolism.

Prostaglandin E(2) (PGE(2)) and LTB(4) synthesis by incubated samples of chorioretina obtained from rabbits' eyes exposed to Neodymium:Yag laser along with these eicosanoids accumulation in the vitreous were measured over one week follow-up period. The effect of NDGA pre-treatment on the COX and the LOX pathways in the laser-injured chorioretina was also assessed. PGE(2) and LTB(4) levels in the vitreous and in the chorioretina incubation medium were quantified using the radioimmunoassay technique with the appropriate antibodies.

LTB(4) in vitro production by rabbits' chorioretina subjected to ND; YAG laser was significantly elevated compared to control, peaking on day 7 to levels 2.45 fold greater than baseline (p < 0.01). PGE(2) formation, following a different pattern, was also enhanced and its maximal level (5.2 fold higher than control, p < 0.01) was achieved at the initial phase (day 1 post laser). Laser irradiation caused also an increase in the two eicosanoids accumulation in the vitreous, which was however not proportional to their production levels. NDGA treatment was associated with a sustained decrease in LTB(4) content in the vitreous, but had no effect on PGE(2) vitreal levels.

Laser irradiation of the rabbits' retina induces an alteration in the LOX metabolic pathway, which is dissociated from the influence on the COX cascade, pointing for the first time to a possible role played by LTB( 4) as a mediator in the chorioretinal inflammatory reaction, with no connection to the role played by PGE(2). NDGA selectively inhibited LOX activity without affecting COX activity.