Reduction of Enhanced Rabbit Intraocular Pressure by Instillation of Pyroglutamic Acid Eye Drops

Abstract

l-Pyroglutamic acid (PGA) is an endogenous molecule derived from l-glutamate. We demonstrate the effects of PGA on intraocular pressure (IOP) in experimentally induced ocular hypertension in rabbits. In the in vitro and in vivo transcorneal penetration studies, the PGA solution (PGA in saline) did not penetrate the rabbit cornea. On the other hand, the penetration of PGA was improved by the addition of zinc chloride and 2-hydroxypropyl-β-cyclodextrin (HPCD), and PGA penetration was enhanced with increasing HPCD concentration. Therefore, PGA solutions containing 0.5% zinc chloride and 5% or 10% HPCD (PGA/ HPCD 5% or 10% eye drops) were used to investigate the effects for IOP in this study. An elevation in IOP was induced by the rapid infusion of 5% glucose solution (15 mL/kg of body weight) through the marginal ear vein or maintaining under dark phase for 5 h. In the both models, the induced elevation in IOP was prevented by the instillation of PGA/HPCD eye drops, and the IOP-reducing effect enhanced with increasing HPCD concentration in the drops. Nitric oxide (NO) levels elevated in the aqueous humor following the infusion of 5% glucose solution, and this increase was also suppressed by the instillation of PGA/HPCD eye drops. In conclusion, the present study demonstrates that the instillation of PGA/HPCD eye drops has an IOP-reducing effect in rabbits with experimentally induced ocular hypertension, probably as a result of the suppression of NO production.

Effect of 5-Oxo-2-Pyrrolidinecarboxylic Acid (PCA) as a New Topically Applied Agent for Dry Eye Syndrome Treatment

“…Interestingly, even if the interpenetration of hyaluronic acid chains with the mucus layer covering the cornea can entrap the PCA molecule on the eye surface, favouring its efficacy, transcorneal permeation does not occur. A similar behaviour was observed by Ito et al [ 17 ] during an ex vivo PCA corneal permeation study using eye drops containing promotion enhancers such as cyclodextrins; they found a substantially higher PCA transcorneal permeation, with a flux of 10.52 nmol cm −2 h −1 , by using a five-fold higher PCA concentration in the donor compartment of the perfusion apparatus. This flux value was approximately 100-fold higher with respect to the values of 0.0761 and 0.1096 nmol cm −2 h −1 measured in our study for PCA alone and the PCA/HA mixture, respectively.…”

“…By virtue of the levels of PCA and PCA-generating enzymes in the skin, PCA has been proposed as a conditioning agent in cosmetic products, even if its absorption through skin is limited. In addition, PCA was proposed for ophthalmic use, both to promote the survival of axotomized retinal ganglion cells in adult mammals as mediated by excitatory amino acid transfer and to reduce intraocular pressure (IOP) in experimentally-induced ocular hypertension in rabbits [ 17 ].…”

Integrated Tear Proteome and Metabolome Reveal Panels of Inflammatory-Related Molecules via Key Regulatory Pathways in Dry Eye Syndrome

“…Pyroglutamic acid is an endogenous molecule derived from glutamic acid; more importantly, it has an intraocular pressurereducing effect. 23 In addition, urocanic acid also displayed antiinflammatory and cytoprotective properties. 24 Another upregulated metabolite, uridine, can restore the health of the ocular surface in a rabbit corneal wound and dry eye model.…”

Effect of Solid Nanoparticle of Indomethacin on Therapy for Rheumatoid Arthritis in Adjuvant-Induced Arthritis Rat

“…Moreover, we reported that the HPβCD was increased the absorption via membrane. 37) Taking these findings together, we hypothesis that high solubility of IMC nano caused the enhancement of BA.…”