Ghrelin and obestatin decreases the IOP in a acute glaucoma model

Purpose The aim of this study is to evaluate the effect of the pro-ghrelin derived peptides in the intra-ocular pressure in animal models of acute glaucoma. Methods The first part of the experimental protocol was the calibration of the Tonovet® used to measure the IOP. In the second part of the protocol we studied, in a rabbit model of acute glaucoma, the effects of ghrelin (10-4M, n=6), des-acyl-ghrelin (10-4M, n=7) and obestatin (10-4M, n=7), as well as the subcellular pathways involved. This model was achieved with an intra-vitreal injection of 20% NaCl. Then, one of the three peptides was sub-conjunctivally injected. Concerning the subcellular pathways, keterolac (a COX inhibitor; 30mg/ml; 500microl; n=7) and L-NAME (a NO synthase inhibitor; 150mg/Kg; 500 microl; n=11) were sub-conjunctivally injected previously to both NaCl and ghrelin injection. All the results were compared to a control group which did not receive ghrelin, des-acyl-ghrelin or obestatin. Results There is a linear correlation between the IOP measured by the Tonovet (Y) and its real value (X), being that underestimated (Y= -0,331 + 0,750X). Our results show that the NaCl injection increases the IOP from 9.9 ± 1.9 to 44.9 ± 4.1. After that ghrelin promotes a decrease of 20,8 ± 5,0 mmHg (decrease of 47,9 ± 11,6%); obestatin promotes a maximal decrease of 15,8 ± 3,9 mmHg (decrease of 37,5 ± 9,4%), while des-acyl-ghrelin does not significantly change IOP. When keterolac or L-NAME are added, ghrelin’s effect is completely blunted. Conclusion Ghrelin showed to promote a decrease of the intra-ocular pressure, independently from GHSR-1a and dependently on NO and prostaglandins. Obestatin also promotes a decrease in the IOP.