Pentoxifylline decreases up-regulated nuclear factor kappa B activation and cytokine production in the rat retina following transient ischemia.

Aim: To investigate whether pentoxifylline (PTX) could influence the increased cytokine gene expression in the retina flowing transient ischemia, and if so, whether it acts through the modulation of nuclear factor kappa B (NF-kappaB) activation.

Methods: Sprague-Dawley rats were randomly divided into three equal groups: control group, saline-treated group, and PTX-treated group. Increased intraocular pressure was applied for 90 min to induce retinal ischemia, and reperfusion was established by lowering the bottle to eye level. The reperfusion period lasted for 48 h. In the PTX-treated group, an initial dose of 20 mg PTX was injected via tail vein at the beginning of reperfusion. Then the rat received infusion of PTX at a rate of 6 mg/kg/h throughout the entire reperfusion period. The retinal tissues were collected at the end of 1, 6, 12, 24, and 48 h of reperfusion, respectively, for biochemical analysis. Histological examination was done on the tissues collected at the end of 48 h after reperfusion.

Results: Histological examination revealed reduction of overall retinal thickness and thinning of the inner retinal layer in saline-treated rats after 48-hour reperfusion. However, PTX treatment significantly reduced the loss of overall retinal thickness and thinning of inner retinal layers. Dramatic increase in NF-kappaB activation, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production and mRNA expression were observed in the saline-treated group after reperfusion, with the peak reached around 12 h. In the PTX-treated group, NF-kappaB activation, TNF-alpha and IL-1beta production and mRNA expression were significantly reduced at each corresponding time point compared to the saline-treated group.

Conclusion: PTX decreased the up-regulated activation of NF-kappaB and the expression of proinflammatory cytokines, TNF-alpha and IL-1beta in rat retinas following ischemia/reperfusion. This may contribute to significantly reduce the loss of overall retinal thickness and thinning of inner retinal layers.