Proliferative vitreoretinopathy : An examination of the involvement of lymphocytes, adhesion molecules and HLA-DR antigens

Abstract

This paper addresses the molecular basis of interactions between leucocytes, other cells in the vitreoretinal environment and extracellular matrix that may underlie the pathogenesis of proliferative vitreoretinopathy. In this study we report the expression of adhesion molecules (CD11a, CD11c, CD18 and ICAM-1), lymphocyte surface markers (CD3, CD4, CD8 and CD22) and HLA-DR molecules in 25 epiretinal membranes obtained from eyes undergoing vitrectomy for the treatment of retinal detachment complicated by epiretinal membrane formation. Retinas from normal cadaveric eyes were used as controls. The results showed that cells expressing the adhesion molecules CD11a, CD11c and CD18 were present in 5 of 25, 17 of 25 and 11 of 23 membranes, respectively. Cells stained with antibodies against intracellular adhesion molecule 1 (ICAM-1) were observed in 24 of 25 membranes, whilst HLA-DR positive cells were seen in all membranes investigated. Immunohistochemical staining revealed that the molecules ICAM-1 or HLA-DR were not only expressed on inflammatory cells but also distributed within the extracellular matrix in several specimens. Lymphocytes expressing CD3 markers were present in 12 of 25 membranes, whilst T lymphocytes expressing CD4 and CD8 markers were observed in 5 of 18 and 12 of 24 membranes, respectively. In contrast, B lymphocytes expressing CD22 molecules were not found in any of the membranes. Leucocyte surface molecules were not expressed in control cadaveric retinas, although occasional cells expressing ICAM-1 were identified in the inner plexiform layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Soluble cellular adhesion molecules in proliferative vitreoretinopathy and proliferative diabetic retinopathy

“…[34][35][36] The additional finding that vitreous levels of sVCAM-1 are similarly elevated is not entirely unexpected, since previous investigations have identified these sCAMs within epiretinal membrane specimens of these proliferative retinal diseases. [15][16][17][18][19] These studies, along with reports of soluble forms of CAMs in other systemic and ocular inflammatory conditions, provided the basis for our study and lend support to its findings. The presence of sCAMs in the vitreous cavity is consistent with other accumulating evidence that inflammatory events play important roles in the pathogenesis of both PVR and PDR.…”

“…ICAM-1, in particular, is a widely-distributed CAM, with previous immunohistochemical studies demonstrating ICAM-1 expression primarily within the cellular regions of PVR and PDR membranes. 15,[17][18][19] In PVR membranes, pigmented cells and nonpigmented cells stain positively for ICAM-1 19 ; in PDR membranes, positively-staining cells include lymphocytes, spindleshaped cells suggestive of fibroblasts, pigmented cells (retinal pigment cells or phagocytic macrophages), as well as the endothelial cells of vascularized membranes. 15 pression is occasionally observed within the extracellular matrix of PVR and PDR membranes, 17,19 consistent with the notion that activated cells may release ICAM-1 to produce sICAM-1.…”

“…[15][16][17][18] Fibrocellular membranes of PVR also express ICAM-1, primarily in highly cellular regions but also within the extracellular matrix. 18,19 The results of these studies suggest a pathogenic role for CAMs in uveitis and in the ultimate development of epiretinal membranes in both PDR and PVR.…”

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

“…Retinal membranes are composed of retinal pigment epithelial cells, glial cells, astrocytes and fibroblasts (Gilbert et al, 1988 ;Jerdan et al, 1989), in addition to infiltrating macrophages and lymphocytes (Limb et al, 1993 ;Weller, Heimann and Wiedemann, 1988). All these cells are bound into a framework of extracellular matrix proteins composed of collagen, fibronectin, vitronectin and laminin (Rodriguez, Newsome and Machemer, 1981 ;Weller et al, 1991 ;Scheiffarth et al, 1988), which confers contractibility to retinal membranes.…”

Changes in Gene Expression of ARPE-19 Cells in Response to Vitreous Treatment

“…These adhesion molecules function to recruit inflammatory cells into a wound site [32][33][34], are known to be increased in the vitreous from patients with PVR and are also present in epiretinal membranes [16][17][18][19]. Our data suggest that in the vitreous model, ARPE-19 cells upregulate genes related to the recruitment of inflammatory cells and may be mimicking the early inflammatory events in PVR.…”