The objectives of this research assume two independent, but converging pathways: (i) the development and implementation of H-1, C-13, Na-23, and P-31 nuclear magnetic resonance (NMR) spectroscopic techniques, including metabolite spatial localization (one- and multi-dimensional """"""""imaging""""""""), for the non-invasive study of lenticular metabolism in both organ culture and in the intact eye (provisionally enucleated globes). The long term goal is to be able to perform NMR measurements in vivo and utilize this information as a probe for lens normalcy. (ii) To establish correlations between NMR lens metabolic data and the functional indices of lens integrity for different cataractogenic stresses. This may permit an identification of lenticular pre-cataractous changes, and thus eventually provide an opportunity for anticataract treatment and the assessment of efficacy. Well defined stresses to the rabbit and human lens in organ culture will be applied (singly and in combination) and the metabolic response evaluated by NMR. Lenticular levels of phosphorus metabolites, glycolytic pathway intermediates, C-13 enriched endproducts of metabolism such as sorbitol and lactate, reduced glutathione levels, and the level of intracellular sodium will be quantitatively monitored by the non-invasive NMR technique. Magnetic relaxation times (T1 and T2) will also be used as probes of lenticular tissue biochemistry. The stress factors will be typical of diabetes (osmotic stress, oscillating high and low glucose levels, pH fluctuations). The progressive lens opacification of the X-ray induced cataract in the rabbit, a system characteristic of the structural and metabolic changes associated with the development of the human senile cataract will also be studied. Indices of lens functional integrity will be evaluated in paralledl and independent collaborative experiments.
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