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 has been created to determine molecular interactions, including lens crystalline interactions that occur in the nucleus of the lens, called Dynamic Light Scattering Device (DLS). Using the new DLS device on animal models of cataract, we have found evidence of this aggregation of proteins as a cataract appears.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 changes in the lens 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 aging, there is a shift of both low and high molecular weight lens proteins toward increasing higher molecular weights, and dramatic shifts at the start of cataract formation. There is also loss of low molecular weight proteins, and more so when a cataract forms, especially in nuclear cararact. In 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. We will soon move into Phase 3 of the study involving use of the DLS device to detect and follow the earliest changes in cataract formation over time (longitudinal study). With this information, we hope to better understand the underlying causes of cataracts and, in the future, develop medications to delay or prevent cataract formation. Finally, we recently explored the use of the NASA-NEI DLS device to study the cornea. Bovine eyes were studied in the normal state as well as treated with chemicals, scraped using cotton swabs with or withour alcohol, and underwent radial keratotomy and photo-refractive surgery.Dynamic and Staticight Scattering techniques were used to study the molecular characteristics opf different layers of the normal cornea as well as after injury. We found that this technique was indeed useful in characterizing different layers of the normal cornea as well as revealed molecular metabolic changes not visible using optical devices such as the slit lamp biomicroscope and therefore holds promise as a tool to study the basis of corneal transparency as well as molecular changes after croneal injury and surgery such as LASIK surgery and Corneal transplantation. Hence we are now moving into Phase 1/Pilot clinical studies using a modified clinical DLS device to study normal and abnormal human corneas in vivo.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000385-03
Application #
6826923
Study Section
(OGVF)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2003
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Cortes, Lizette M; Mattapallil, Mary J; Silver, Phyllis B et al. (2008) Repertoire analysis and new pathogenic epitopes of IRBP in C57BL/6 (H-2b) and B10.RIII (H-2r) mice. Invest Ophthalmol Vis Sci 49:1946-56
Datiles 3rd, Manuel B; Ansari, Rafat R; Reed, George F (2002) A clinical study of the human lens with a dynamic light scattering device. Exp Eye Res 74:93-102