We recently described spontaneous cataract formation in the Dahl salt-sensitive rat. Preliminary data demonstrating a decreased incidence of cataract development when salt-sensitive rats are maintained on a normal, rather than high sodium diet suggests that cataractogenesis may be linked to hypertension in this genetic model. In addition, our finding of altered lenticular and aqueous humor electrolyte composition in salt-sensitive rats with cataracts, suggests the possibility that cataract formation may be the consequence of altered lenticular ionic transport. We now propose to evaluate this possibility through measurements of lenticular sodium and potassium transport in salt-sensitive rats with cataractous lesions. Passive ionic fluxes will be assessed through studies of lenticular 22Na uptake and 86Rb efflux. Active sodium and potassium transport will also be determined through 22Na efflux and 86Rb uptake studies. Furthermore, we propose to evaluate the possibility that changes in ionic transport may precede cataract formation, and that such changes may also parallel the development of hypertension in the salt-sensitive rat. To this end' longitudinal studies of lenticular ionic transport will be carried out in rats beginning at weanling age. Although a defect in lenticular calcium transport could also explain our observations, normal lenticular calcium transport processes have not been clearly defined, and calcium flux studies in the lens are of limited value. Nevertheless, we will examine the possibility that cataract formation may be associated with increased lenticular calcium permeability through measurements of 45Ca uptake. Finally, we propose to determine if cataracts can be prevented by preventing the development of hypertension in salt-sensitive rats. In this manner we will determine if elevated blood pressure, per se, is a necessary condition for cataract formation. Our observations of cataracts associated with hypertension is novel to both ophthalmic and hypertension research. The proposed studies address major issues that are central to understanding the possible relationship between cataractogenesis and hypertensive disease.
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