The objective of this proposed research is to perfect the clinical laser light scattering spectroscopy technique so that it can be routinely used by ophthalmologists and eye researchers to provide the early detection and quantitative diagnosis of cataract formation, and for the development and evaluation of anti-cataract drugs. Upon completion, we will have practically the first quantitative, macromolecular-level clinical tool for the lens, both for clinical and researches of the lens. Laser light scattering spectroscopy is a safe, non-invasive technique, that enables sensitive observation of the Brownian motions of crystallin proteins within the intact lens. From the temporal fluctuations of light scattered from the crystallin proteins, it is possible to detect slight alterations, such as aggregation and synthesis, which occur in the cytoplasm. Eleven years has elapsed since the technique was first developed and applied on rabbits in our laboratory. The technique has been improved since then toward a clinical usage, and indeed its safety and uniqueness as a quantitative and extremely sensitive clinical tool have been established. (Safety approved by NIH, MGH in the USA, and Ministry of Welfare in Japan.) However, its functional capacity as a routine ophthalmological tool is not yet fully realized. We rationalize the source of its imperfection as follows: irreproducibility of the observed location within the lens, sophistication in its principle, and difficulty of analysis and interpretation of data. We now believe that the recent advances in laser spectroscopy, and the physics of protein solutions and gels, for which we believe that we have some contribution, are substantial and allow us to resolve these difficulties. We, thereby, propose to perfect the clinical technique in its opto-electronic and mechanical structure, the science of extremely highly concentrated macromolecular solution, gels, and cytoplasm, the method of analysis, and interpretation and presentation of data.
| Peetermans, J A; Foy, B D; Tanaka, T (1987) Accumulation and diffusion of crystallin inside single fiber cells in intact chicken embryo lenses. Proc Natl Acad Sci U S A 84:1727-30 |
| Peetermans, J A; Nishio, I; Ohnishi, S T et al. (1987) Single cell laser light scattering spectroscopy in a flow cell: repeated sickling of sickle red blood cells. Biochim Biophys Acta 931:320-5 |
| Peetermans, J; Nishio, I; Ohnishi, S T et al. (1986) Light-scattering study of depolymerization kinetics of sickle hemoglobin polymers inside single erythrocytes. Proc Natl Acad Sci U S A 83:352-6 |
