DISTINCT PROFILES OF PHOSPHODIESTERASE ISOZYMES IN CULTURED-CELLS DERIVED FROM NONPIGMENTED AND PIGMENTED OCULAR CILIARY EPITHELIUM

Alterations in either cyclic AMP (cAMP) or cyclic GMP (cGMP) may modul ate the production of aqueous humor by the ciliary epithelium of the e ye, thereby affecting intraocular pressure. We have found distinct pro files of phosphodiesterase (PDE) isozyme activity in cultured cells de rived from bovine pigmented ciliary epithelium (PE) and cells derived from human nonpigmented ciliary epithelium (NPE), as well as correspon ding differences in the effects of selective PDE inhibitors on the acc umulation of cAMP and cGMP. In NPE cells, but not in PE cells, the maj or peak of PDE activity was stimulated by Ca++/calmodulin-stimulated ( PDE I), and hydrolyzed both cAMP and cGMP. In contrast, PE cells conta ined a cGMP-specific PDE V not found in NPE cells. Rolipram, a selecti ve inhibitor of PDE IV, was more potent and effective than the selecti ve PDE III inhibitor Cl-930 at potentiating intracellular cAMP accumul ation in both cell types. Zaprinast, a selective inhibitor of PDE V, p otentiated cGMP accumulation in PE but not in NPE cells. The results s uggest that selective PDE inhibitors may modulate aqueous humor produc tion by pigmented and nonpigmented ciliary epithelium, the two cell ty pes may have different functional roles, and selective modulation of t heir functions may be possible. Furthermore, there may be distinct rol es for intracellular calcium in regulating cGMP and cAMP in pigmented vs. nonpigmented ciliary epithelial cells.