Intravitreal Injection of TGFβ Induces Cataract in Rats

PURPOSE In a previous study, it was determined that TGFbeta induces cataractous changes in the rat lens in vitro. The purpose of the present study was to determine whether the introduction of biologically active TGFbeta into the vitreous stimulates cataractous changes in the rat lens in situ. METHODS TGFbeta was injected into the vitreous of the left eye of anesthetized adult male Wistar rats. The right eye received sterile vehicle as a control. Three to four months after injection, animals were killed, and lenses were enucleated and examined for cataractous changes. RESULTS All lenses from control eyes remained transparent and maintained normal cellular architecture throughout. In contrast, lenses from TGFbeta-injected eyes displayed cloudiness in the cortex. In some lenses, distinct opacities were also apparent at the equator and extending some distance toward the anterior and posterior poles. Histologically, the opacities corresponded to subcapsular plaques containing aberrant cells and accumulations of extracellular matrix. In addition, cortical fibers in the anterior and posterior of all lenses displayed variable degrees of swelling, and many retained their nuclei. In some regions, the fiber cells appeared to have degenerated to form large homogeneous areas. The cellular architecture of the equator of these lenses was also disrupted and, in the most severe case, no bow zone was apparent with nucleated cells extending to the posterior pole. CONCLUSION The introduction of active TGFbeta into the vitreous induced lenses to undergo cataractous changes. In addition to the TGFbeta-induced changes in the epithelium that were reported previously, cataractous changes observed in this study also involved the lens fiber cells and resembled changes observed in human posterior subcapsular and cortical cataracts.