The mechanisms of apoptosis are strongly dependent an cell-cell interactions typical of organized tissues. Experimental studies of apoptosis using a histotypical preparation of retinal explants are reported in the present article. We found that various characteristics or apoptosis are selectively associated with retinal cell death depending on cell type. stage: of maturation. aad means of induction of apoptosis. Among these were: (1) thr requirements of protein synthesis; (2) the role of cAMP: (5) the expression of certain apoptosis-associated proteins: and (3) the sensitivity to excitotoxicity. modulation of protein phosphatases and calcium mobilization. Dividing cells undergo apoptosis in response to several inducers in specific phases of the cell cycle, and in distinct regions within their pathway of interkinetic nuclear migration. Recent post-mitotic cells are selectively sensitive to apoptosis induced by blockade of protein synthesis. while both proliferating and differentiated cells are more resistant, We also studied the association of several proteins, some of which play critical roles in the cell cycle, with both differentiation anti apoptosis in the retinal tissue. Detection of ct II cycle markers did not support thr hypothesis that retinal cells re-enter the cell cycle on their pathway to apoptosis although some proteins associated with cell proliferation re-appeared ill degenerating cells. The transcription factors c-Jun, c-Fos and c-Myc were found associated and apoptosis in retinal cells. but their sub-cellular location In apoptotic bodies is not consistent with their canonical functions in the control of gene expression. The bifunctional redox factor/AP endonuclease Ref-1 and the transcription factor Max are associated with progressive cell differentiation, and both ate down-regulated during ct-Il death in the retina. The data suggest that Ref-1 and Max may normally function as negative modulators of retinal apoptosis, The results indicate that nuclear exclusion of transcription factors and other important control proteins is a hallmark of retinal apoptosis. Histotypical explants mag. be a choice preparation for the experimental analysis of the mechanisms or. apoptosis. in the context both or. cell-cell interactions and of. the dynamic behavior of uf developing cells within the organized retinal tissue. (C) 1998 Elsevier Science Ltd. All rights reserved.