Transforming growth factor beta in experimentally detached retina and periretinal membranes

This study was undertaken to determine whether experimental retinal detachment produces changes in retinal localization of three isoforms of transforming growth factor beta (TGF-beta) 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-beta localization during retinal degeneration. ELISA assay for TGF-beta1 and -beta2 was performed on samples of fluid from the vitreous chamber to determine whether active or inactive TGF-beta was present. Confocal microscopy was used to localize TGF-beta1, -beta2 and -beta3 and the type II TGF-beta receptor at the various detachment durations. Following experimental retinal detachment the levels of TGF-beta2 increased in the vitreous chamber but no changes in TGF-beta1 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-beta1 and -beta2 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-beta2 antibody. Some increased immunostaining for TGF-beta3 was observed in the ganglion cell bodies. Labeling for the TGF-beta 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-beta protein localization. These results demonstrate that retinal detachment induces the synthesis and secretion of TGF-beta2. 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.