- Search for factors and/or conditions preventing or postponing age-related changes in ocular tissues.
- To find out whether normal and/or enhanced levels of alphaA-crystallin promote resistance against conditions which might cause damage to eye tissue and/or its constituents and whether already distorted eye tissue has a diminished level of the protecting protein.
In summary it will be investigated whether alphaA-crystallin plays a key role in the protection of eye tissues. Such studies in tissue culture and in situ will be a first step in the finding of those factors which are involved in prolongation of the lifespan of highly differentiated organs as the eye.
- The finding of effective treatments for age-related and other degenerative retinal disorders by examination of the normal retina as well as the retina of humans and animals with well characterized degenerations and by developing retinal cell transplantation procedures.
- Good descriptions of the different nosological entities.
- Factors determining differentiation, structure and survival of retinal cell transplants as well as vital components of photoreceptor differntiation.
- Molecular characterization of K+ channels in the human lens and ageing effects on the channel properties.
- The examination of the permeation properties of sclera; a profile of the age related functional, biochemical and structural changes in the sclera will be constructed.
The eye contains a variety of tissues of which the time course of their ageing processes differs considerably. Studying these processes in the different ocular tissues might lead to understanding of the pathogenesis of a number of age-related eye diseases such as: primary open angle glaucoma or macular dystrophy of the retina; particularly if compared with slow rate ageing processes of corneal or lenticular tissues which remain transparent nearly through the entire human life-span. In the work programme lens, retina, cornea and sclera will be explored as systems for the study of age-related changes at the cellular and molecular level. The effects of external and internal factors upon the ageing process will be studied with a major focus on the protective action of the chaperone-like aB-crystallin which provides stress resistance and thermotolerance to many cell types and is involved in correct folding of a number of cellular proteins and enzymes. The action of alphaB-crystallin will also be pursued by creating transgenic mice either carrying the alphaB-crystallin gene or the alphaA-crystallin gene and overexpressing the corresponding proteins in a variety of nonlenticular tissues. The combined efforts are aimed, not only at a better understanding of ageing per se, but will presumably facilitate the search for new therapeutic concepts in order to prevent at least some forms of blindness and/or reduce the number of glaucoma patients who will develop blindness.
Funding SchemeCSC - Cost-sharing contracts
6500 HD Nijmegen
OX2 6AW Oxford