The role of heat shock protein 27 in the survival and regeneration of adult aging rodent retinal ganglion cells

Many neurological disorders, including spinal cord and brain injuries, stroke, Alzheimer¿s dementia, Parkinson¿s disease and glaucoma, are all characterized by the death of specific populations of central nervous system (CNS) neurons. Our laboratory is interested in identifying molecules that maintain and restore the function of injured neurons in the CNS. The expression of heat shock protein 27 (Hsp27) is associated with the survival of some injured neurons; however, its specific roles in the retina and other brain regions remain unknown. Using the rat visual system as an experimental animal model of CNS injury, as well as purified retinal ganglion cells (RGCs) in culture, we will determine the effects of Hsp27 on the survival and regeneration of injured RGCs. Our preliminary results are promising, demonstrating that Hsp27 expression is increased when cellular apoptosis is triggered and showing successful transfection of RGCs in culture. Furthermore, we have found that in vivo many RGCs successfully regenerating into a peripheral nerve graft also express Hsp27. Our proposed experiments will test whether Hsp27 enhances survival and regeneration of injured RGCs. Experiments are also included to determine the mechanism of Hsp27 action by overexpressing a dominant-interfering mutant of Hsp27. Understanding the effects of Hsp27 on the survival and regeneration of injured neurons is important in developing novel strategies for treating common neurological and retinal diseases.