Retinal inflammation after penetrating corneal surgery: the role of TNF-α and IL-1β inhibition.

Abstract

Purpose : To assess the effect of corneal surgical injury on retinal inflammation and neuronal damage, and to investigate the neuroprotective effect of TNF-α and IL-1β inhibition after the injury

Methods : Three corneal injury models were employed using C57BL/6 mice: a) penetrating corneal suture using a 10-0 vicryle suture, b) autologous PKP, and c) autologous PKP combined with lens removal. Treatments included: infliximab (10mg/Kg), kineret (10mg/Kg), or the combination administered immediately after the procedure. Evaluation of corneal and retinal inflammation was performed 24 hours after the procedure using qPCR, flow cytometry, and immunohistochemistry.

Results : All corneal injuries induced significant retinal inflammation and retinal cell damage. Inflammation was associated with peripheral CD11b⁺ CD45⁺ monocyte infiltration into the retina and was more severe in PKP + lens extraction with marked upregulation of TNF-α mRNA (39-fold), IL-1β (275-fold) and IL-6 (56-fold). Administration of anti-TNF-α or anti-IL-1β reduced retinal inflammation, however concomitant TNF-α + IL-1β inhibition was more effective in suppressing TNF-α mRNA expression to 1.5-fold, IL-1β to 7-fold, and IL-6 to 15-fold after PKP + lensectomy as well as retinal cell loss (p<0.05).

Conclusions : Corneal surgical injuries can cause retinal inflammation and subsequent damage to retinal neurons. The severity of the damage is proportional to the severity of the injury and can be reduced by prompt TNF-α and IL-1β inhibition. These findings may help explain increased susceptibility to glaucoma after acute ocular injury, such as PKP or keratoprosthesis surgery.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.