| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Cells respond to adverse changes in the environment by increasing the levels of a group of proteins referred to as heat shock, or stress, proteins. It is suggested that these proteins provide protection against the stress-induced formation of denatured proteins andmay even facilitate their renaturation. The role of 70 kilodalton stress protein (SP70) in the visual system is supported in the report, that showed the expression of stress protein in the retina, which was induced by a brief period of hyperthermia in the whole animal, correlated with a marked reduction in retinal susceptibility to subsequent light damage. The particular function of SP70 in human retinal tissue remains to be elucidated. To explore the physiological functions of this protein, its localization in the normal and stressed human retina was examined. We compared the immunolocalization of SP70 in normal human retina and in one with absolute glaucoma. The normal human retina showed diffuse immunostaining throughout.
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The outer nuclear layr was poorly immunostained. However, the retina with absolute glaucoma, demonstrated obvious immunostaining in the inner segments and in the nuclei of the photoreceptor cells. Results of this study suggest an induction of SP70 in the human retina stressed by increased intraocular pressure. In the experiment with rat retina, earlier work has shown that its content of SP70 can be increased by raising the anesthetized rat's body temperature to 41-42ﾟC and that during the time of the elevated SP70, the retina is resistant to light damage. On the basis of this connection, we evaluated the levels of SP70 in each of the layrs of the retina of young (3 month) and old (20 month) Fisher 344 rats under normal conditions and after being challenged by a brief period of hyperthermia. The aim was to determine if a disturbance in retinal SP70 might correlate with the well documented gradual loss of photoreceptors in the Fisher rat retina as a function of increasing age. During the post-hyperthermia period, the 20 month old rats showed consistently lower levels of SP70 immunoreactivity than the 3 month old rats in all of the retinal layrs that include the various parts of the photoreceptor cells. Since SP70 is known to protect cells from the lethal effects of methabolic stress, decline observed in the older rats suggests that there is an impairment of the retinal response to metabolic stress which may render the photoreceptors more susceptible to the light damage and destruction. Further work will be required to determine if this defect is a causative factor or an epiphenomenon of age-lerated retinal degeneration. Less
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