Proinflammatory Cytokines in a Mouse Model of Central Retinal Artery Occlusion

Abstract

Purpose: : To characterize the temporal changes in the expression of pro-inflammatory cytokines in the retina and serum following the induction of central retinal artery occlusion (CRAO) in a mouse model.

Methods: : CRAO was induced by laser activation of intravenously injected rose bengal. Retinal mRNA was analyzed for the expression of MIP-2, IL-6 and TNF-α using real-time RT-PCR. Cytokine levels in serum were measured by ELISA. Analysis was performed at various time intervals from induction of CRAO.

Results: : In the retina, MIP-2 and IL-6 expression decreased 3 hours after induction of CRAO (0.35 and 0.51 of control levels, respectively), and increased thereafter, peaking at 12 hours (by 15- and 23-fold of control levels, respectively). By 7 days, levels were again mostly undetectable. TNF- α expression increased at 3 hours (by 4.7-fold of control levels) and declined to control levels at 7 days. In the serum, MIP-2 level peaked at 1 hour and decreased to control levels at 12 hours. IL-6 levels increased between 3 and 12 hours and decreased at 24 hours. TNF- α showed an early peak at 1 hour and a late rise at 1 and 7 days.

Conclusions: : The changes in cytokine expression in the retina and serum during ischemia induced by retinal artery occlusion resemble previous reports in humans and may affect the severity of damage and, thereby, outcome. The absence of IL-6 early after the ischemic event and its later expression may indicate a protective role. MIP-2 and TNF-α may be involved in worsening the ischemic damage. Therefore, therapeutic strategies should take the timely modulation of these cytokines into account.

Keywords: ischemia • cytokines/chemokines • retina