Transport of Timolol and Tilisolol in Rabbit Corneal Epithelium

The purpose of this study is to characterize the transport of tilisolol and timolol through the corneal epithelium, which is believed to be a tight barrier of ocular drug absorption. Cultured normal rabbit corneal epithelial cells (RCEC) were used to investigate drug transport. Primary RCEC were seeded on a filter membrane of Transwell-COL? insert coated with fibronectin and grown in Dulbecco\u27s modified Eagle\u27s medium/nutrient mixture F-12 with various supplements. Beta-blocker permeability through the RCEC layer was measured to assess the transcellular permeability coefficient (Ptranscell) in the absence or presence of inhibitors. The transcellular permeability of tilisolol was dependent on drug concentration although timolol showed no concentration dependency. Tilisolol flux from the apical to the basal side was larger than in the opposite direction although timolol showed no direction dependency. The transcellular permeability of tilisolol from the apical to the basal side was inhibited by sodium azide, tetraethylammonium, quinidine, taurocholic acid, guanidine and carnitine. Tilisolol had an active mechanism in uptake to the corneal epithelium, probably by the organic cation transporter family, although timolol predominantly permeated via passive diffusion. This RCEC system was useful to characterize the ocular permeation mechanism of drugs

Transport of Acebutolol through Rabbit Corneal Epithelium

The purpose of this study is to characterize transport of acebutolol through the corneal epithelium. Cultured normal rabbit corneal epithelial cells (RCEC) were used to investigate the drug transport. Primary RCEC were seeded on a filter membrane of Transwell-COL? insert coated with fibronectin and were grown in Dulbecco\u27s modified Eagle\u27s medium/nutrient mixture F-12 with various supplements. Measurements of acebutolol permeability through RCEC layer were carried out to assess transcellular permeability coefficient (Ptranscell) in the absence or presence of inhibitors. Paracellular permeability coefficient (Pparacell) was calculated by permeability coefficient of hydrophilic drugs (Pcell). The transcellular permeability of acebutolol from apical side to basal side (A-to-B) showed concentration-dependency. The acebutolol flux in the A-to-B direction was smaller than that of opposite direction. Sodium azide, verapamil, and cyclosporin A enhanced the transcellular permeability of acebutolol in the A-to-B direction. Acebutolol permeability through an excised rabbit cornea was also increased by verapamil. Thus, it was suggested that acebutolol was actively secreted via P-glycoprotein in a corneal epithelium

Menopause and dry eye. A possible relationship.

The hormonal status and in particular sex steroids play a role in the ocular surface homeostasis and function, during the whole life and in both sexes, accomplished by estrogenic and androgenic receptors located on corneal and conjunctival epithelia and Meibomian gland. The ocular surface is an integrated unit and any dysfunction results in a scarce or unstable preocular tear film zhich produces dry eye, a chronic inflammatory condition with increasing incidence as people get older but always more frequent among females. In post-menopausal women endocrine changes join the aging effects in the pathogenesis of dry eye, but still it remains controversial whether estrogen of androgen dedificency or their imbalance impair ocular surface function. Another questionable issue concerns the efficacy of hormonal replacement therapy in the amelioration of dry eye symptoms and recovery of tear function, since the scientific literature stands in between a therapeutic or a promoting effect of eye dryness. Therapy of dry eye is usually based upon topical administration of tear substitutes; estrogen or androgen-based eye drops represents a promising innovative treatment based upon important scientific rationale