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Masatsugu Nakamura, Yuko Takaoka-Shichijo, Tadahiro Murakami; The Stimulatory Mechanism of Diquafosol Tetrasodium on Tear Fluid Secretion in Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3766.
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The treatment of dry eye requires improvement of the quality and quantity of the tear film on the ocular surface. It has been reported that the P2Y2 receptor agonist, diquafosol tetrasodium, stimulates tear fluid secretion and mucin secretion in vitro and in vivo. However, the action mechanism of this stimulatory effect has yet to be fully understood. We have, thus, investigated the stimulatory mechanism of diquafosol tetrasodium on tear fluid secretion in rabbits.
Rabbit tear fluid secretion was measured by the Schirmer test. The extracted samples from the Schirmer test strips were used to estimate the tear protein concentration. The tear protein content was calculated by multiplying the protein concentration by the volume of tear fluid. To explore the main target tissue of diquafosol tetrasodium, we examined protein secretion from the isolated rabbit lacrimal gland. In addition, the short-circuit current was evaluated as an index of water secretion from the rabbit conjunctiva.
Application of diquafosol tetrasodium stimulated tear fluid secretion in a dose dependent manner and maximal secretion was observed 15 min after instillation. Diqaufosol tetrassodium did not affect protein concentration in the tear fluid, however, the protein content increased in proportion to the applied doses as the tear volume increased. With the isolated rabbit lacrimal gland, diquafosol tetrasodium did not affect protein secretion up to a concentration of 1 mM. However, it stimulated water secretion from the isolated rabbit conjunctiva in a concentration-dependent manner. This stimulatory effect of diquafosol tetrasodium was inhibited by pretreatment with a calcium chelating agent.
These results suggest that diquafosol tetrasodium may act mainly on the conjunctiva by stimulating tear fluid secretion via an increase in the concentration of intracellular calcium.
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