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Posted: Jan 04, 2008
Nanotechnology treatment for most common cause of blindness becomes feasible
(Nanowerk Spotlight) The human eye is an amazing organ. It is small, the eyeball itself weighs only about 7 grams, and it is amazingly sensitive. The eye can detect a single photon. The eye can be quicker then a race car - the young human eye can focus from infinity to 7cm in 350 milliseconds - but slow enough to witness a snail crawling across a beach. The eye can capture objects at various different angles, such as birds flying overhead or a person walking right beside you. Because the eye is such a complex optical system, it is not surprising that the list of diseases and infections that can endanger our vision is a long one. One common age-related condition is cataract. Cataract is caused by alterations in the protein structure of the lens which result in light scattering. The lens can then no longer transmit a clear picture to the retina where it can be processed and sent through the optic nerve to the brain. By age 65, over 40% of people have a cataract. Cataract is the most common cause of blindness in the world, although it is treatable. While cataract surgery is the most successful medical procedure, the inability to control penetration of the pharmacological agents into the lens and target specific intracellular biochemical pathways has impeded the success of pharmacological treatment of cataracts. Researchers are now studying the application of nanotechnology to eye lens diseases, in particular for new methods for visualizing and targeting specific intracellular mechanisms within the eye.
Dr. Wei Chen, a nanotechnologist and an assistant professor of Nano-Bio Physics at the University of Texas at Arlington, approached a lens physiologist (Dr. Barbara K Pierscionek of the University of Ulster) and an ophthalmologist (Ronald A. Schachar, M.D., Ph.D. of the University of Texas at Arlington) to study the biochemical causes of cataractogenesis – the process of cataract formation.
According to Chen, emerging nanotechnologies have a great potential to uncover the cause of cataract and may provide a good solution for its treatment.
"The lens is comprised of tightly packed epithelial cells and lens fibers, enclosed in a thin capsule" Schachar and Pierscionek explain to Nanowerk. "Although the lens fibers have few organelles, their protein content is very high. The lens consists of 35% protein and 65% water. In addition, there are three classes of proteins in the human lens. Lens transparency is thought to depend on short-range order of these protein classes within the lens. Even slight changes in lens protein shape, structure or to the overall protein arrangement and the interaction of the proteins with water can cause the scattering that reduces lens transparency, which results in a cataract."
The arrangement of proteins that is needed to maintain transparency is still not fully understood, as to date it has not been possible to tag the proteins inside an intact lens. Nanotechnology now offers us this potential.
In a preliminary study, the scientists demonstrate that passive diffusion of fluorescent nanoparticles (quantum dots) may be used to study the basic structure and biochemistry of cortical lens fibers.
Fluorescent micrograph of a wet mount of human cortical lens fibers from a 34 year old donor, demonstrating the intracellular presence of (a) red fluorescent nanoparticles and (b) green fluorescent nanoparticles, 40x objective (Reprinted with permission from IOP Publishing).
The researchers used intact porcine lenses from five-month-old pigs, intact human lenses obtained from three donors aged 41, 42 and 45 years, and sections of human lens cortex obtained from four donors aged 11, 19, 32, and 34 years were incubated for 72 hours at 7°C in aqueous solutions of green (566 nm) and red (652 nm) fluorescent water soluble cadmium tellurium (CdTe) nanoparticles.
"We were able to demonstrate that CdTe quantum dots diffused into the lens capsule and the cortical lens fibers but did not pass through the intact lens capsule" says Chen. "Since dextan, which has a diameter at least twice that of the nanoparticles, can passively diffuse through the lens capsule, the negative charge, carboxyl group, and/or the alkaline pH of the nanoparticles may have prevented the
nanoparticles from passing through the capsule. Future studies are required to determine the critical variables necessary for the diffusion of nanoparticles through the lens capsule."
This study shows that nanoparticles can be used as a method for studying intracellular structure and biochemical pathways within the lens capsule and cortical lens fibers to further understand cataractogenesis.
This and subsequent studies may lead to a medical treatment for primary and secondary cataracts where nanoparticles may serve as a carrier for chemotherapeutic agents.
Chen further points out that this study offers the prospect of identifying, for the first time, the early structural changes that precede opacification and may even lead to the identification of protein classes that may be predominately involved. In addition, fluorescent nanoparticles may be used to enhance visualization of the lens capsule during cataract surgery.