| In response to injury, the retina undergoes dramatic cytoarchitectural changes and responds by forming a "glial scar" in and around the affected area, perhaps attempting to limit further tissue damage. Proliferation, growth, and migration of glial cells (gliosis) in the detached retina leads to irreversible histological changes that, eventually, will prevent reattachment to the retinal pigment epithelium, resulting in blindness.; In the first chapter, the magnitude of the proliferative response was quantified in two animal models of RD using an antibody that binds to an antigen present only in proliferating cells. These data were then compared with previous data where autoradiography was used to measure the proliferative response. This study was published previously (see Geller et al., 1995).; The second chapter focuses on analysis of activated signaling molecules and transcription factors that may be involved in regulating proliferation, particularly with respect to Muller cells. In this set of experiments, early changes in protein expression and activation of specific signaling pathways were analyzed using a variety of both cellular and molecular techniques. c-Fos and c-Jun (AP-1) were found to be up-regulated in response to detachment within 2 hours, and a mammalian mitogen activated protein (MAP) kinase is activated within minutes of RD. These data provide insight into the speed of cellular reactivity, and have significant clinical implications beyond that of pathological RD.; Recent data suggest that brain derived neurotrophic factor (BDNF) may help photoreceptors retain their structural integrity and promote regeneration of the light sensitive outer segments. In the third chapter, in order to clarify BDNF's mechanism of action in the retina, recombinant-human BDNF was injected into normal eyes. Minutes to days later, the tissue was removed and processed for immunohistochemical and Western analysis. Injection of BDNF resulted in increased MAP kinase signaling and AP-1 expression in ganglion, amacrine, and Muller cells.; It is undeniable that combined loss of photoreceptors and induction of gliosis impairs vision and impedes visual recovery following RD. The data presented here suggest that a variety of early changes takes place after RD, and that these changes correlate well with cellular responses such as injury induced proliferation. |
