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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences A Study Section (VISA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wake Forest University Health Sciences
Schools of Medicine
United States
Zip Code
Dean, D O; Tytell, M (2001) Hsp25 and -90 immunoreactivity in the normal rat eye. Invest Ophthalmol Vis Sci 42:3031-40
Dean, D O; Kent, C R; Tytell, M (1999) Constitutive and inducible heat shock protein 70 immunoreactivity in the normal rat eye. Invest Ophthalmol Vis Sci 40:2952-62
Beasley, T C; Tytell, M; Sweatt, A J (1997) Heat shock protein 70 in the retina of Xenopus laevis, in vivo and in vitro: effect of metabolic stress. Cell Tissue Res 290:525-38
Andersson, C; Brunso-Bechtold, J; Tytell, M (1994) Immunocytochemical and ultrastructural characterization of type 1 astrocytes and 0-2A lineage cells in long-term co-cultures. Brain Res 646:100-17
Tytell, M; Barbe, M F; Brown, I R (1993) Stress (heat shock) protein accumulation in the central nervous system. Its relationship to cell stress and damage. Adv Neurol 59:293-303
Andersson, C; Tytell, M; Brunso-Bechtold, J (1993) Transplantation of cultured type 1 astrocyte cell suspensions into young, adult and aged rat cortex: cell migration and survival. Int J Dev Neurosci 11:555-68
Yamaguchi, K; Gaur, V P; Tytell, M et al. (1991) Ocular distribution of 70-kDa heat-shock protein in rats with normal and dystrophic retinas. Cell Tissue Res 264:497-506
Yamaguchi, K; Barbe, M F; Brown, I R et al. (1990) Induction of stress (heat shock) protein 70 and its mRNA in rat corneal epithelium by hyperthermia. Curr Eye Res 9:913-8
Tytell, M; Barbe, M F; Gower, D J (1989) Photoreceptor protection from light damage by hyperthermia. Prog Clin Biol Res 314:523-38
Barbe, M F; Tytell, M; Gower, D J et al. (1988) Hyperthermia protects against light damage in the rat retina. Science 241:1817-20