Proliferative Diabetic Retinopathy Membranes Research Articles

PROLIFERATIVE ACTIVITY IN EPIRETINAL MEMBRANES

Epiretinal membranes occur in a number of pathogenetically different diseases, such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), macular pucker, and ischemic, inflammatory, and degenerative vitreoretinal disorders. The formation of epiretinal membranes is characterized by the proliferation of histogenetically different cell types. Knowledge of the proliferating potential of surgically excised epiretinal membrane tissue might be clinically relevant to determine which patients face a high risk of recurrences. The monoclonal antibody Ki-67 specifically stains a cell-cycle associated nuclear antigen that is only expressed by cells in the G1, S, and G2/M phases of the cell cycle. With this antibody, the actively proliferating growth fraction can be stained in frozen tissue samples of surgically removed epiretinal membranes by the indirect immunoperoxidase method. In this study, the monoclonal antibody Ki-67 was used to screen 37 epiretinal membranes in PVR, PDR, macular pucker, and in recurrences after intraocular silicone oil tamponade for the presence of actively proliferating cells. Additionally, the number of Ki-67 positive cells in a section of the membrane was quantitatively set in relation to the total cell number of this section. Thus a proliferative index (PI) was ascribed to each membrane as a decimal quotient. The proliferative indices can be graded into four subgroups for missing or very low (PI less than 0.1), low (PI 0.1-0.3), moderate (PI 0.3-0.6), and high (PI greater than 0.6) proliferative activities. High proliferative activities were found in 4 of 5 PVR membranes, in 9 of 14 PDR membranes, in 6 of 11 recurrent membranes after intraocular silicone oil tamponade, and in 2 of 6 macular pucker membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitronectin and proliferative intraocular disorders. II. Expression of cell surface receptors for fibronectin and vitronectin in periretinal membranes

Several cell types participate in the formation of vitreoretinal traction membranes in proliferative intraocular disorders. The communication between these cells involves hormones, growth factors, and the interaction with extracellular matrix molecules. We have previously demonstrated a partial colocalisation of two potent mediators of cell attachment, fibronectin and vitronectin, in periretinal membranes from patients with proliferative vitreoretinopathy (PVR). We found a similar pattern of vitronectin and fibronectin deposition in proliferative diabetic retinopathy (PDR) (n = 6). Now we show the expression of the corresponding cell surface receptors, integrins, for fibronectin and vitronectin by proliferating cells in 22 periretinal membranes, including traumatic (n = 8) and idiopathic (n = 8) PVR as well as PDR membranes (n = 6). Integrins are membrane receptors for extracellular matrix macromolecules which are involved in such basic biological phenomena as embryogenesis and metastasis. Future studies on the pathogenesis of vitreoretinal proliferation will have to focus on the initiation, maintenance, and regulation of this intercellular communication network involving attachment proteins and integrins.

Cellular components of proliferative vitreoretinal membranes

To understand the pathogenesis of proliferative vitreoretinal membrane formation which occurs in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), etc., accurate identification of the cellular components of the membrane is needed. This study was performed to identify cellular components of the membranes by means of immunohistochemical technique. 11 proliferative vitreoretinal membranes which were surgically obtained from 7 eyes with PVR and 4 eyes with PDR were stained with monoclonal antibodies against cytokeratin, glial fibrillary acidic protein (GFAP), or vimentin using immunoperoxidase technique (ABC method). In the PVR membranes, mean cell positivities for cytokeratin, GFAP and vimentin were 48%, 1% and 92%, respectively and in the PDR membranes, 0%, 5% and 93%, respectively. The above results suggest that retinal pigment epithelial cells and fibroblasts are major cellular components of PVR membranes, and that mesenchymal cells are major cellular components and glial cells are minor cellular components of PDR membranes.

Immunostaining of Preretinal Membranes for Actin, Fibronectin, and Glial Fibrillary Acidic Protein

The frequency and extent of immunostaining for actin, fibronectin (FN), and glial fibrillary acidic protein (GFAP) were determined in 37 preretinal membranes (PRMs) obtained at vitrectomy from 35 patients with proliferative diabetic retinopathy (PDR) (n =16), proliferative vitreoretinopathy (PVR) (n =18), or idiopathic macular pucker (MP) (n = 3). All three proteins were detected in the vast majority of specimens (actin, 86%; FN, 95%; GFAP, 96%), although the extent of staining varied for each. Actin-FN co-localization was observed in all diagnostic groups on comparison of adjacent sections and in double-labeled sections. The extent of actin staining did not correlate with clinical grading of PRM contraction. In PDR membranes, FN staining was low overall, but proportional to the vascular content of the PRM. Fibronectin staining of PVR membranes was greater, and extensive even in avascular specimens. In MP membranes, most cells were GFAP-positive, whereas in PDR and PVR specimens, GFAP staining was variable. The lack of correlation of clinical contractility and membrane composition, as studied in this article by immunostaining, indicates that other factors must play significant roles in determining membrane behavior.