|
International
Tables for Crystallography Volume F Crystallography of biological macromolecules Edited by M. G. Rossmann and E. Arnold © International Union of Crystallography 2006 |
International Tables for Crystallography (2006). Vol. F. ch. 1.3, p. 21
Section 1.3.4.3.3. Blindness
aBiomolecular Structure Center, Department of Biological Structure, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195-7742, USA |
The main causes of blindness worldwide are cataract, trachoma, glaucoma and onchocerciasis (Thylefors et al., 1995![[link]](/graphics/greenarr.gif)
). Trachoma and onchocerciasis are parasitic diseases that destroy the architecture of the eye; they were discussed in Section 1.3.4.1. The other two are discussed here. During cataract development, the lens of the eye becomes non-transparent as a result of aggregation of crystallins, preventing image formation. Crystal structures of several mammalian beta- and gamma-crystallins are known, but no human ones yet. In glaucoma, the optic nerve is destroyed by high intra-ocular pressure. One way to lower the pressure is to inhibit carbonic anhydrase II, a pivotal enzyme in maintaining the intra-ocular pressure. On the basis of the carbonic anhydrase crystal structure, researchers at Merck Research Laboratories were able to guide the optimization of an S-thienothiopyran-2-sulfonamide lead into a marketed drug for glaucoma: dorzolamide (Baldwin et al., 1989).
References
Baldwin, J. J., Ponticello, G. S., Anderson, P. S., Christy, M. E., Murcko, M. A., Randall, W. C., Schwam, H., Sugrue, M. F., Springer, J. P., Gautheron, P., Grove, J., Mallorga, P., Viader, M. P., McKeever, B. M. & Navia, M. A. (1989). Thienothiopyran-2-sulfonamides: novel topically active carbonic anhydrase inhibitors for the treatment of glaucoma. J. Med. Chem. 32, 2510–2513.Google Scholar
Thylefors, B., Negrel, A. D., Pararajasegaram, R. & Dadzie, K. Y. (1995). Global data on blindness. Bull. WHO, 73, 115–121.Google Scholar
