Interleukin-1-beta changes the expression of metalloproteinases in the vitreous humor and induces membrane formation in eyes containing preexisting retinal holes

Abstract

Purpose: Proliferative vitreoretinopathy occurs when cells migrate into the vitreous humor, where they proliferate and produce a membrane composed of extracellular matrix. Interleukin-1-beta (IL-1-beta) may be involved in these processes because it is chemotactic and mitogenic, and it stimulates metalloproteinase production. In the present study, the effects of intravitreally injected IL-1-beta on retinal membrane formation and the associated changes in metalloproteinase content of vitreous humor were examined.

Methods: Rabbit eyes were injected with IL-1-beta in a buffer, with or without the prior creation of retinal holes. Control eyes received the buffer alone or no injection, with or without retinal holes. Animals were examined by slit lamp biomicroscopy and indirect ophthalmoscopy for 1 month. Zymography was performed on a portion of vitreous humor to assess collagenase content, and the remaining tissue was subjected to histologic analysis.

Results: Intraocular IL-1-beta induced perilimbal vessel engorgement, keratic precipitates, synechiae, flare, lens deposits, optic disk hyperemia, and granulomatous formations that gradually subsided during the first week. Intravitreal injection of IL-1-beta in eyes with preexisting retinal holes additionally induced membrane formation. Zymographic analysis of vitreous humor from animals sacrificed 24 hours after IL-1-beta injection showed a 100-kd and a 65-kd gelatinase, whereas control vitreous humor contained predominantly a single gelatinase species of approximately 65 kd. Retinal holes did not affect IL-1-beta induction of the 100-kd gelatinase.

Conclusions: IL-1-beta induces a 100-kd gelatinase in the vitreous humor and epiretinal membrane formation in eyes containing preexisting retinal holes. The presence of retinal holes and abnormal production of cytokines may lead to a cascade of events, including aberrant extracellular matrix remodeling, that result in proliferative diseases of the eye.