Immunochemical studies of epiretinal membranes using APAAP complexes: Evidence for macrophage involvement in traumatic proliferative vitreoretinopathy

Abstract

Proliferative vitreoretinopathy is characterized by cellular proliferations in the periretinal space resulting in traction retinal detachment. Numerous cellular elements and connective tissue components have been identified by morphologic criteria as well as immunochemical techniques. In this study, we used the recently introduced APAAP (alkaline phosphatase -anti-alkaline phosphatase) immunostaining procedure to identify macrophages, T-lymphocytes, the structural proteins flbronectin, vimentin, and cytokeratin, and a proliferating cell antigen, in eleven human epiretinal membranes obtained during vitreoretinal surgery. Our results confirm that the pathologic processes in PVR are not immunologically mediated, but reveal the features of physiologic wound healing and scar formation.Posttraumatic PVR seems to be characterized by a severe initial inflammatory reaction as evidenced by the presence of numerous macrophages, whereas idiopathic PVR, as a complication of retinal detachment, may be caused by different mechanisms in the early pathogenesis.

Iron-Binding Proteins in the Human Vitreous: Lactoferrin and Transferrin in Health and in Proliferative Intraocular Disorders

“…Certain types of macro phages, which exhibit immunoreactivity for lactoferrin, have been observed [23], but this is not the case with the macrophages in pre retinal membranes. These cells could be identified in some of the membrane speci mens examined in this study, as described previously [10], but did not yield a positive lactoferrin label. We have already discussed possible interactions between macrophages and transferrin in the metabolism of iron and some implications for the proliferative processes in PVR [2], Iron-loaden lactoferrin is similarly taken up by macrophages.…”

“…We have already discussed possible interactions between macrophages and transferrin in the metabolism of iron and some implications for the proliferative processes in PVR [2], Iron-loaden lactoferrin is similarly taken up by macrophages. The number of lactoferrin-binding sites on monocytes-macrophages is much higher than the number of transferrin-binding sites, although the functional significance of this finding is unclear [24], Lactoferrin displays avid iron binding at a lowered pH in areas of inflammation and is released by polymor phonuclear leukocytes under these circum stances [4], However, although there is (ster ile) inflammation during the early stages of PVR, and although macrophages can be identified in preretinal membranes [10], no lactoferrin could be labeled in this study. The pathways of iron bound by transferrin and lactoferrin, respectively, are probably different [24].…”

“…Antirabbit IgG serum-alkaline phos phatase (Sigma A 0407) and antigoat IgG serum-alka line phosphatase (Sigma A 7650), respectively, or the avidin-biotin system, using biotinylated antirabbit IgG serum (Dakopatts E 353) and avidin-alkaline phosphatase (Dakopatts D 365), diluted in Tris-buffered saline/bovine serum albumin were used as a label for the primary antihuman lactoferrin serum. Macrophages were labeled using an APAAP detection system as described previously [10].…”

Macrophages Acquire Fibroblast Characteristics in a Rat Model of Proliferative Vitreoretinopathy

“…Multiple reports have implied a major role of macrophages in driving the pathogenesis of PVR [20][21][22][23] . Not only clinical studies of epiretinal membranes from patients with PVR document the presence of macrophages, but also experimental data demonstrate that macrophages can mediate the development of PVR.…”

Proliferative vitreoretinopathy ? is it anything more than wound healing at the wrong place?

“…We think that this differentiation can be similarly reduced to mononuclear phagocytes on the one hand and fibroblastic cells of different origin on the other hand. The important contribution of mononuclear phagocytes is recognized in general wound repair [55,67,68], in the mediation of inflammatory lesions [44], in experimental retinal wound healing [75], after krypton laser photocoagulation [90], and in human PVR [60,117,118,119,121]. Whether the mononuclear phagocytes in PVR are derived predominantly from the peripheral blood, the transformation of RPE cells, microglia [87], or other local resident phagocytes, has not been clarified yet [121], although the question was probably first raised more than fifty years ago [37].…”