Cataracts are the foremost cause of blindness in the world and currently can be treated only by surgical removal. Surgery, although easily available and safely performed in the U.S., is not easily available nor safely performed in many undeveloped regions in the world like Asia, Africa, the Middle East and South America. Hence we are studying ways to treat cataracts non-surgically, and a new device promises to help us find out what happens to the human lens that may cause cataracts, which will then help us find a cure for cataracts. One theory on the cause of cataracts is that some factors such as sunlight or lack of protective anti-oxidant vitamins may cause the proteins inside the lens to aggregate to form opaque high molecular weight "aggregates". Recently, a device (the Dynamic Light Scattering device or DLS), has been created to determine molecular interactions, including lens crystalline interactions that occur in the nucleus of the lens. Using the new DLS device on animal models of cataract, we have found evidence of this lens protein aggregation as a cataract develops. Preliminary studies have shown its potential in the detection of the earliest changes occurring in cataract, at the stage where anticataract treatment would theoretically be most effective in reversing, delaying or preventing cataracts. A new miniaturized version of this device has been developed by NASA using lower energy lasers and offered for further development and clinical testing at the NEI. We mounted the DLS device successfully on the Keratoscope, which had a 3-D aiming system to enhance repeatability. We recently conducted a pilot study on normal human volunteers (Phase 1) to evaluate the usefulness and reproducibility of this instrument for quantitating lens changes, and found good reproducibility. We also determined that the most useful parameter to use is mean particle size derived from particle size distribution. We are now in Phase 2 of this project, studying clinical changes in the human lens in vivo due to aging (age related changes), as well as molecular changes found in the three representative types of cataracts (nuclear, cortical and PSC). We found that with normal aging, there is a shift of both low and high molecular weight lens proteins toward increasing higher molecular weights. During cataract formation, we have observed loss of low molecular weight proteins and dramatic increases in high molecular weight proteins, so that all the proteins could end up in a single large molecular weight peak, especially in nuclear cararact. In some cortical and posterior subcapsular cataracts, there are marked molecular changes in the lens nucleus even when the nucleus remains clear and does not seem to be affected. These data will help characterize molecular changes in the human lens associated with normal aging as well as those associated with cataract formation. These in vivo, non invasive lens aging and cataract studies were not possible because we had no way to detect and quantify these early lens and cataract changes in the molecular level. This new easy to use device offers a new, sensitive and precise method to study conditions and medications that can either cause cataract or prevent cataract. Preliminary analysis of the data shows good correlation between DLS and Clinical Lens Grading data, suggesting that the DLS method can determine the severity of clouding of the lens (cataract) objectively without the need of an ophthalmological exam, making it also useful in field studies. We are continuing to study how the resulting complex data represents molecular lens changes. If successful then, the development of this technique will help us conduct future clinical cataract studies of all sorts, with great sensitivity and accuracy, as well as for shorter durations and at lower expense. The resulting information will help us to better understand the underlying causes of cataracts and help us develop and test new treatments to delay, reverse or prevent cataract formation.