Transforming Growth Factor Beta in Experimentally Detached Retina and Periretinal Membranes

Abstract

This study was undertaken to determine whether experimental retinal detachment produces changes in retinal localization of three isoforms of transforming growth factor beta (TGF-β) and the type II receptor for this protein. Neural retinas of young adult cats were detached from the pigment epithelium. Survival times varied from 3 to 28 days to study the temporal course of TGF-β localization during retinal degeneration. ELISA assay for TGF-β1 and -β2 was performed on samples of fluid from the vitreous chamber to determine whether active or inactive TGF-β was present. Confocal microscopy was used to localize TGF-β1, -β2 and -β3 and the type II TGF-β receptor at the various detachment durations. Following experimental retinal detachment the levels of TGF-β2 increased in the vitreous chamber but no changes in TGF-β1 were detected. Levels were increased 3 days post-detachment and continued throughout the 28 day period studied. The most prominent changes in immunolocalization occurred in the TGF-β1 and -β2 isoforms. Increased immunolabeling was seen in Müller cells and ganglion cell bodies. Hypertrophied Müller cell processes formed periretinal membranes that were heavily labeled by the TGF-β2 antibody. Some increased immunostaining for TGF-β3 was observed in the ganglion cell bodies. Labeling for the TGF-β type II receptor was seen in Müller cells, ganglion cells and the inner and outer plexiform layers in both normal and detached retinas. Changes in localization of the receptor after detachment paralleled the changes seen in TGF-β protein localization. These results demonstrate that retinal detachment induces the synthesis and secretion of TGF-β2. Growth factor and receptor immunolabeling were increased in Müller cells suggesting that this isoform is involved in the retinal gliotic response and may contribute to the development of proliferative vitreoretinopathy.