Damage to retinal photoreceptors as a consequence of accidental exposure to bright light, physical trauma to the eye, or disease is a serious problem because, once the photoreceptors die, they cannot be replaced. At present, little can be done to reduce photoreceptor degeneration following damage. This proposal is designed to investigate the potential influence of a distinctive cellular reaction to acute stress or damage, known as the heat shock or stress response, on photoreceptor stress tolerance. The heat shock response refers to the dramatic increase in the synthesis of a small group of proteins that occurs in most cells when they are under acute stress due to any one of a variety of factors, such as hyperthermia, heavy metal intoxication, or anoxia. The production of those heat shock proteins (HSPs) correlates with the aquisiton of stress tolerance in many cells. Recently, this investigator has shown that the synthesis of HSPs can be stimulated in rat retina by raising its body temperature 4 to 5 degrees C (the equivalent of a high fever) and that, at the same time, the retinal photoreceptors show a dramatic increase in survival after exposure to a damaging intensity of light. The experiments described herein are aimed at determining how to optimize the hyperthermia-induced increase in photoreceptor stress tolerance, whether it can enhance photoreceptor survival after they are damaged, and what specific role the HSPs have, if any, in the capacity of photoreceptors to survive exposure to damaging levels of light.
