Endothelin Immunoreactive Cells in Human Proliferative Vitreoretinopathy

Abstract

Abstract: : Purpose: Retinal astrocytes normally express endothelin-1 (ET-1), a vasoactive and mitogenic peptide. Glial cells are an important component of membranes developing during proliferative vitreoretinopathy (PVR). However, the relative contribution of astrocytes and Müller cells is at present unknown. Therefore, we studied ET-1 immunohistochemical expression in tissue specimens obtained during surgery for PVR. Methods: Tissue specimens (n = 13) were fixed in a paraformaldehyde-picric acid mixture. Cryostat sections were submitted to immunoenzymatic and immunofluorescent procedures using antibodies against ET-1, glial fibrillary acidic protein (GFAP) and smooth muscle actin (SMA). Consecutive sections were stained with neutral red. Results: Surgical PVR samples exhibited different histological patterns ranging from a cell-rich "deconstructed" retina to a cell-poor fibrotic membrane. ET-1 immunoreactive cells were found in every specimen but, their distribution and frequency varied according to the histological pattern. In regions of "deconstructed" retina, ET-1 immunoreactivity appeared in a thin layer beneath the vitreal surface. These ET-1 labeled cells also exhibited GFAP immunoreactivy. However, doubly labeled cells were a minor proportion of retinal GFAP positive cells, suggesting that they represented a minor glial subpopulation. Membranes also exhibited variable proportions of ET-1 immunoreactive cells. Co-localization with GFAP was seldom found within the membranes. By contrast, some ET-1 immunoreactive cells were also labeled by the SMA antibody. Some membrane ET-1 positive cells showed no colocalization with GFAP or SMA. Conclusions: ET-1 immunoreactive cells were present in PVR specimens. Their distribution and co-localization with other markers suggest that there are at least three different phenotypes. The retinal subpopulation co-expressing GFAP probably represents modified astrocytes, whereas membrane cells co-expressing SMA can be identified as myofibroblasts. Since studies from several laboratories have detected SMA in astrocytes, a transition between retinal astrocytes and myofibroblasts during PVR membrane development could be taken into consideration. No specific markers have been found for the third phenotype, which could perhaps represent modified macrophages.

Keywords: retina • proliferative vitreoretinopathy • growth factors/growth factor receptors