Fos, the product of the cellular oncogene c-fos, is rapidly synthesized by cells in response to a wide variety of extracellular stimuli. It is one of a family of DNA-binding proteins, termed third messengers, that are thought to couple extracellular signals, from hormones, neurotransmitters, and growth factors to longer-term alterations in gene expression. In the central nervous system (CNS), there is evidence that Fos participates in adaptations to changes in neuronal activity and responses to injury. The proposed studies use the rabbit retina as the primary experimental model. The overall goals are (1.) to understand the role of Fos in the complex mechanism by which gene expression is regulated in the CNS in response to chemical signals and to pathologic insults and (2.) to develop the foundation of knowledge on which to base the use of Fos immunohistochemistry as an anatomic marker of neuronal activity. Immunohistochemistry will be the primary technique employed to examine the production of Fos and related proteins in response to light stimuli, to neurotransmitter agonists and antagonists, and to growth factors. A major aspect of the project will be to exploit Fos immunohistochemistry to unravel the early events in the response of the nervous system to injury, particularly of the retina to detachment from the pigment epithelium. These events may be of importance in understanding the pathogenesis of proliferative vitroretinopathy, a condition which limits the therapy of retinal detachment. This research is therefore intended to contribute to understanding normal CNS processes, such as plasticity and neuronal adaptations to alterations in synaptic input, as well as responses to pathologic insults.
| Sharp, F R; Butman, M; Wang, S et al. (1992) Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine. J Neurosci Res 33:605-16 |
| Sagar, S M; Edwards, R H; Sharp, F R (1991) Epidermal growth factor and transforming growth factor alpha induce c-fos gene expression in retinal Muller cells in vivo. J Neurosci Res 29:549-59 |
