Distribution of cytokine proteins within epiretinal membranes in proliferative vitreoretinopathy

Abstract

This study reports on the immunohistochemical staining for cytokine proteins of 26 epiretinal membranes obtained from eyes undergoing surgery for the treatment of proliferative vitreoretinopathy. All specimens were investigated for the distribution of staining for interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma) and interleukin-2 (IL-2). The results showed that 22 of the membranes (85%) stained for TNF alpha not only intracellularly but also in the extracellular matrix. This contrasts with the findings that only 2 membranes stained for IL-1 alpha and that another 3 were positive for IL-1 beta. Staining for the cytokines IL-6 and IFN gamma was also observed in 9 and 7 membranes respectively. None of the specimens investigated stained with antibodies to IL-2 or control antibodies, and none of three normal retinas stained with any of the antibodies used. Pre-absorption of anti-cytokine antibodies with the corresponding human recombinant cytokines abolished staining of cells and extracellular matrix. The present findings support growing evidence that cytokine-mediated pathways of inflammation are involved in the pathogenesis of proliferative vitreoretinopathy, and draw attention to the possibility that interaction between extracellular matrix-bound cytokine and inflammatory leucocytes or resident cells of the retina may promote the development and perpetuation of this condition.

Predominance of MMP-1 and MMP-2 in Epiretinal and Subretinal Membranes of Proliferative Vitreoretinopathy

“…In vivo, these cytokines are also able to enhance MMP production in vitreous humour (Kosnosky et al, 1994). This is of special relevance to the pathogenesis of PVR, as TNFα is the predominant cytokine found in the extracellular matrix of epiretinal membranes (Limb et al 1994a(Limb et al , 1994b. It is therefore conceivable that TNFα may be responsible for the release of MMPs and TIMPs within the detached retina.…”

“…APAAP staining was performed as previously described (Limb et al, 1994a). Briefly, tissue sections were washed in Tris buffered saline pH 7n4 (0n05  Tris in 0n15  NaCl : TBS) and incubated for 3 hr with primary antibody.…”

Caspase-8–Mediated Apoptosis in Human RPE Cells

“…[7][8][9] TNF-␣ activates the extrinsic apoptotic pathway and the nuclear transcription factor (NF)-B survival pathway through TNF receptors. 10 In many cells, NF-B upregulates antiapoptosis proteins and thereby prevents TNF-␣-mediated apoptosis.…”

Interleukin 1 in Experimental Proliferative Vitreoretinopathy

“…Our data do not exclude the possibility of IL-1 being released by cells within PVR mem branes and acting locally or the involvement of other proinflammatory cytokines [20].…”