Molecular biology of retinal development and retinal degeneration

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To ascertain the roles of TGF-beta superfamily in retinal development, the changes of the expression patterns of these receptors during development of the normal rat retina were observed immunohistochemically. Activin type I receptor and BMP type IB receptor were first detected in P6 and P3 retinas at protein levels, respectively, and activin type II receptor was First detected in P0 retina The other receptors (TGF-beta type I and II receptors, activin type IB receptor, BMP type IA and II receptors) were detected at E17. The period of PO-P9 corresponded to the dynamic changes in the rat retinal development. These results suggest that the expression of TGF-beta superfamily is regulated along with retinal development and may be related to retinal developmentTo investigate molecular mechanisms of retinal precursor cells, retinoblastoma (RB) cell lines were used. RB cell lines are resistant to TGF-beta due to the absence of TGF-beta binding to RB cells. To elucidate the mechanisms of resis … More tance to TGF-beta, we studied the expression of TGF-beta receptors and Smad family (transducers for TGF-beta family), and signal transduction pathways for TGF-beta RB in cell lines. In RB cell lines, either TGF-beta type I or II receptors (TbetaR-I, TbetaR-II, respectively) was not expressed on the cell surface. TbetaR-I mRNA was expressed. TbetaR-II mRNA was not detected, however, was induced by sodium butyrate. Mutation analysis revealed no mutation in the coding region of TbetaR-II gene. Smad family member mRNAs (Smad 2, 3, 4) were expressed. Transcription activation by TGF-beta addition was rescued only by the transfection of both TbetaR-I and TbetaR-II.The lack of response to TGF-beta is caused by the lack of TGF-beta receptor expression on cell surface. Some parts of signal transduction pathways are conserved in RB cells.To investigate pathogenesis of retinal degeneration in Royal College of Surgeons (RCS) rats in vivo, the expression of intracytoplasmic signal transducers for apoptosis. Apoptosis signal-regulating kinase 1 (ASK1) in involved in the mitogen-activated protein (MAP) kinase cascade. p38 and c-Jun-amino-terminal kinase (JNK) with MAP kinase activity were downstream component of ASK1. RCS rat retina of 4W and 5W, p38 and JNK were expressed in the inner segments in both RCS rats. However, the expression of ASK1, p38-p or JNK-p in the inner segments decreased significantly in RCS rats, which suggests that the signal transduction from ASK1 through p38 and/or JNK was abrogated in RCS rat retinal photoreceptor cells. Signal transduction from ASK1 through p38 and/or JNK was abrogated in retinal photoreceptor cells in RCS rat. Less