We have shown major changes in the crystallins and other proteins in the lenses of transgenic mice in which the HIV-1 protease is linked to the alpha A-crystallin promoter. The homozygous animals get cataracts on day 23 to 24 after birth. Previous work has shown that the HIV-1 protease activates cysteine protease(s) and this protease cleaves the lens proteins. Thus, the HIV-1 protease is responsible for the activation of the cataract process but not responsible for the subsequent opacification of the lens that is caused by other proteases. Two-dimensional gels of the proteins from the lenses of the transgenic animals have shown multiple alterations in the isoelectric points and molecular weights of the crystallins. Using this technique we have been able to document the first changes in the lens start around day 17. These changes are observed in the alpha and some of the beta crystallins. These changes correspond to the alterations seen in the nucleus of the lens by scanning microscopy. Comparing the modification of the proteins caused by cataract formation to changes seen with the normal aging mouse lens, we have shown that cataractogenesis is not merely """"""""accelerated"""""""" aging of the crystallins as has been suggested by others. Although many of the protein modifications seen with aging in the lens are present in the transgenic lens during cataract formation, there are distinct proteins changes present in the normal lens that are not present in the cataractous ones. Our work shows that the process of cataract formation is not inherently an aging process, but one in which characteristic protein modifications can be observed.
