Transforming growth factor beta mediates apoptosis in the ganglion cell layer during all programmed cell death periods of the developing murine retina

Transforming growth factor beta (TGF-beta) is an extracellular signaling molecule known to mediate programmed cell death (PCD) in the developing retina. In the present study, we investigated the expression profiles and activity levels of TGF-beta ligand and TGF-beta receptors (T beta R) during the successive physiological PCD periods of the developing postnatal mouse retina. The peak of T beta R expression levels - revealed by Western Blots and MLEC assays - coincided with the main periods of postnatal (P) retinal murine PCD at P2, P9, and P15. Immunocytochemical studies showed that the localization of the T beta Rs is restricted to the ganglion cell layer. Application of a neutralizing anti-TGF-beta antibody to E15 and P9 retinal cultures resulted in a significant decrease in the number of TUNEL-positive neurons specifically in the ganglion cell or prospective ganglion cell layer. Treatment of P2 and P15 organotypic murine retinal wholemount cultures with exogenous recombinant TGF-beta significantly increased cell death levels. In the P15 retina, where PCD affects ganglion cells and photoreceptors, TGF-beta induced cell death of large retinal ganglion cells, whereas small ganglion cells and photoreceptor neurons remained unaffected. Our data indicate that TGF-beta mediated apoptosis during all postnatal retinal PCD phases specifically affects the fate of retinal ganglion cells. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.