Effects Of Pirenzepine Solution On Form Deprivation Myopia

In recent years, the prevalence of myopia is increasing in many parts of the world, especially in Asia. Although spectacle lenses and kinds of keratorefractive surgery can correct refractive errors of myopia, all these methods are helpless for the elongation of the eyeball. Therefore, a radical therapy to myopia is in urgent need. In 21 century, some countries used 0.5%-1% atropine, a non-selective cholinergic antagonist to treat the adolescent myopia, but its unavoidable side-effects such as mydriasis, photophobia, decreased of accommodation, allergic conjunctivitis etc, limit its extensive clinical used.In recent over ten years, it was found that the prienzepine, a M1-selective cholinergic antagonist was indeed very efficient in blocking the experimental and adolescent myopia, though its mechanism was not clear. The previous studies investigated the efficacy of pirenzepine in experiment myopia by intravitreal and subconjunctiva injection routes, through these ways, the intraocular concentration was high, but they were traumatic and unsuitable for the long-term of clinical uses. When topically applied, the corneal permeability rate was very low and could not reach theeffect concentration in blocking the myopia.In order to solve these problems, the present study added sodium hyaluronic and azone in 2% pirenzepine eye-drop solutions, the concentration of pirenzepine in the aqueous humor were determined by high pressure liquid chromaography (HPLC), furthermore, the efficacy of the pirenzepine eye-drop solutions on form deprivation myopia(FDM) was determined in the guinea pigs.1. Corneal permeability of topically applied pirenzepine solutionsMaterials and methods Sixty-three New Zealand white rabbits were divided into 3 groups. Each group received either 2% pirenzepine, 2% pirenzepine with 0.1% azone , or 2% pirenzepine with 0.1% hyaluromic acid . Eyedrops were instilled one drop every 5 minutes for six times. Aqueous samples were obtained from each group at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 24.0hour after the last drop, respectively. Concentration of pirenzepine in these samples was determined by the HPLC. Stimulation symptom of rabbit eyes was also observed.Result Aqueous humor concentration of both 2% pirenzepine with 0.1% azone and 2% pirenzepine with 0.1% hyaluronic acid were significantly higher than that of pirenzepine group, and their bioavailability were 23 times and 3.4 times that of pirenzepine group . No obvious stimulation symptom was found in the three rabbit groups after eye-drop applying.Conclusion Azone group has the best corneal permeability , hyaluronic acid group the second, both higher than pirenzepine group. This result indicates that azone and hyaluronic acid could be used in pirenzepine eye-drop solution to increase corneal permeability for further clinical use.2. The efficacy of pirenzepine solutions in preventing FDM in guinea pigs. Materials and methods twenty-four 1-week-old Guinea pigs were divided into 4 groups randomly. After having refraction measurements, all the right eyes were monocularly deprived (MD) using translucent goggles for 40 days, In group I , the deprived eyes received topical administration of vehicle as the control. The other three? of the MD groups(II, III, IV )were topically treated with 2% pirenzepine, 2% pirenzepine with 0.1% azone ,and 2% pirenzepine with 0.1% hyaluronic acidrespectively. The left eyes were used as normal control without any treatment. Ocular refraction and biometric measurement were made at the end of the experiment. All eyes were finally enucleated for histopathological examination to evaluate the possible toxic effects of pirenzepine.Result In group I, II, III, 40days of MD produced -6.17D> -5.38D and -4.09D of myopia and 0.6mm ,0.53and 0.59mm axial dimensions respectively. There were great significant differences of refractive error and axial dimension between the experiment eyes and the controls. In group IV there were no significantly differences of refractive error and axial dimension between experiment eyes and contralateral eyes. Conclusion 2% pirenzepine and 2% pirenzepine with 0.1% hyaluronic acid eye-drop solutions were not effect for reduction of FDM. But topically used 2% pirenzepine with 0.1% azone eye-drop solution can prevent FDM in this mammalian model guinea pigs by inhibiting the elongation of axial dimension and no obvious damage to the ocular tissues.