Transparency is the fundamental structural feature that distinguishes lens cells from all other mammalian cells. In lens cells, transparency is established when spatial fluctuations in cytoplasmic density become small relative to the wavelength of light, which minimizes light scattering. The size of the spatial fluctuations depends on molecular interactions between cytoplasmic constituents of lens cells. Changes in these molecular interactions can produce loss of transparency and formation of cataracts. The present application is a continuation of studies on development and maintenance of lens transparency. The previous proposal began studies on development of lens transparency, identified reversible stages of lens opacification and discovered completely new reagents for preventing opacification in rats exposed to Irradiation. The present application proposes continued research on development of transparency to characterize molecular interactions responsible for normal development and maintenance of lens transparency in vivo. and to test the new reagents on several cataract models: galactosemic, selenite, streptozotocin and R.C.S. (Royal College of Surgeons rat) In the proposed research plan, the studies will (1) evaluate quantitatively the spatial fluctuations in lens cytoplasm during normal development of transparency in embryonic lens cells; (2) characterize the molecular interactions responsible for normal spatial fluctuations in transparent lens cells, and (3) demonstrate the effectiveness of new phase separation inhibitors on the prevention of cataracts in vivo. The working hypothesis is that direct analysis of the spatial fluctuations in lens cells during development will lead to an understanding of molecular interactions that regulate transparent cell structure.
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