Activated T lymphocytes in epiretinal membranes from eyes of patients with proliferative diabetic retinopathy.

Background: To investigate the potential contribution of immune-mediated processes to the development of proliferative diabetic retinopathy (PDR), an immunohistochemical study was undertaken to characterize the infiltrating immune cells in epiretinal membranes from the eyes of patients with PDR.

Methods: A total of 18 PDR epiretinal membrane specimens obtained surgically from pars plana vitrectomy were studied by using a panel of monoclonal antibodies against T lymphocytes (CD4 and CD8), interleukin-2 (IL-2) and interleukin-2 receptors (IL-2R).

Results: Twelve of 18 specimens (67%) contained CD4-positive cells and 13 of 18 (73%) contained CD8-positive cells.

Proliferation and activation of vascular endothelial cells in epiretinal membranes from patients with proliferative diabetic retinopathy. An immunohistochemistry and clinical study.

In the present study, we investigated the status of proliferation and activation of vascular endothelial cells in epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) by means of immunohistochemical techniques and compared the findings with the main clinical features of the patients. The results showed that of 21 vascularized membranes, 17 (81%) contained proliferating endothelial cells (positive for proliferating vascular endothelial cell marker EN 7/44) and 19 (90%) were positive for endothelial cell activation marker anti-VCAM-1; Furthermore, by using a double-staining technique we found that in 15 of the 17 cases (88%) the proliferating vascular endothelial cells were activated (expressing VCAM-1). Of the 18 type I diabetics, 15 (83%) contained activated proliferating endothelial cells, whereas in the 3 type II patients, only 1 membrane contained activated proliferating endothelial cells, Preoperatively, 18 patients had severe vitreous hemorrhage, among whom 15 (83%) contained proliferating endothelial cells, which were activated in 13 cases, and 16 patients had tractional retinal detachment, among whom 12 contained proliferating endothelial cells, which were activated in 11 cases.

Expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on proliferating vascular endothelial cells in diabetic epiretinal membranes.

The present study demonstrated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), the proliferating status of the neovascular endothelial cells, and the activation of vascular endothelial cells bearing the two cell adhesion molecules in diabetic epiretinal membranes by using double immunofluorescence and APAAP techniques. The results showed that ICAM-1 was detected in 36 out of 40 (90%) proliferative diabetic retinopathy epiretinal membranes, VCAM-1 was found in 32 out of 40 cases (80%); in 21 out of 26 (81%) vascularised membranes the endothelial cells of the new vessels in the membranes were still in a proliferative stage (positive for proliferating endothelial cell marker EN 7/44) and, further, in 20 out of 26 cases (77%) ICAM-1 was detected on the proliferating endothelial cells and VCAM-1 was found in 21 cases (81%). The expression of cell adhesion molecules, especially ICAM-1 and VCAM-1 in diabetic epiretinal membranes suggests that cell to cell interactions may play a significant role in the development of PDR membranes.

The effect of retinoic acid on chemosensitivity of PA-1 human teratocarcinoma cells and its modulation by an activated N-ras oncogene.

Combination of chemotherapeutic drugs with agents that induce cell differentiation is a possible means of improving cancer chemotherapy. To explore this approach we used 4 cell lines established from the human teratocarcinoma-derived cell line PA-1; 2 retinoic acid (RA)-sensitive lines compared to 2 RA-resistant lines transformed by an activated N-ras oncogene. Equal numbers of colony-forming cells were exposed for 72 hr to 10(-6)M RA and subsequently to a range of concentrations of cisplatinum, etoposide or bleomycin.