An Experimental Study On Effect Of Intracamerally Administered Adreno-Medullin On Decreasing Intraocular Pressure In Conscious Rabbits

Objective To study whether intracameral administration of ADM could lower intraocular pressure (IOP) in conscious rabbit eyes with normal IOP and ocular hypertension, and the concentration of cAMP and cGMP in aqueous humor was determined so as to investigate its therapeutic effect on glaucoma and its ocular hypotensin mechanism.Methods Acute ocular hypertension was induced by rapid intravenous injection of 5% glucose solution 15ml·kg-1. IOP was measured periodically after various doses of ADM were injected into eyes with normal IOP and ocular hypertension until it returned to the baseline level.Radioimmunoassay was used in determination of the level of cAMP and cGMP in aqueous humor 6h after administration of ADM.ResultsIn conscious rabbits, (10~-6~10~-4)mol/L ADM intracamer-ally administered profoundly reducing normal IOP, and the maxinum effect was observed at 4~8h(Bonferroni test, P<0.05). The ocular hypotensive effect of ADM was concentration-dependent from 5×10~-7mol/L to 10-4mol/L ADM1. (repeated measured ANOVA, P<0.05, exception of 5×10~-7mol/L ADM). 10~-5mol/L ADM caused a more rapid decrease in IOP than the other groups with the maxinum effect reaching 1.33KPa, which maintained for 72h. 10-4mol/L ADM had an moderate effect on IOP, but its action persisted for the longest time 120h. 2. In conscious rabbits, intracameral injection of 5×10~-7mol/L~10-4mol/L ADM concentration-dependently suppressed the increments of IOP induced by glucose-injection as well .The suppression of (10~-6~10~-4)mol/L ADM was statistically significant(repeated measured ANOVA, P<0.05). The peak effect of the optimum concentration of 10~-5mol/L ADM was 1.45KPa compared with the contralateral control IOP, while the IOP depressions of 10~-6mol/L and 10~-4mol/L ADM were 0.88KPa and 0.60KPa respectively. 3. The cAMP concentration in aqueous humor of the ADM(10-6~10-5 mol/L)-treated eyes were (10.94±1.33)pmol/ml and (11.09±1.72)pmol/ml (n=6), that of the cGMP were (12.75±2.91)pmol/ml and (12.41±1.61)pmol/ml (n=6). There was no statistically significant difference between ADM-and vehicle-treated eyes. Conclusion Varioue doses of ADM administered intracamerally can decrease normal IOP and suppress acute IOP elevation induced by intravenous injection of glucose, which suggest ADM might play a role in controlling IOP. Its signal transduction system(s) remain to be determined since the cAMPand cGMP systems are not involved in ocular hypotension effect.