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Lindsey H Millard, Andriy Pashko, Claes Bavik, Ryo Kubota; Prostaglandin EP4 Increases Outflow Facility in Calf Eyes Using a Whole Eye Organ Perfusion (WEOP) Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):555.
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© ARVO (1962-2015); The Authors (2016-present)
Models using animal eyes are relevant for glaucoma research. Between species, however, physiologic and pharmacologic signaling differences present obstacles in determining the tissue most analogous to humans for studying intraocular pressure (IOP) regulation through the conventional outflow pathway. Here, we aimed to determine whether enucleated calf eyes responded similarly to a selective prostaglandin EP4 (PG-EP4) agonist when perfused into a whole-eye ex-vivo model as previously published using mice and human eyes.
Paired post-mortem calf eyes received within 4 hrs and prepared for organ-culture were perfused at 10 mmHg constant pressure. Once a stable baseline was established, the contents of the anterior chamber were exchanged with either drug (L-902.688, 16 nM) or vehicle (PBS with glucose). After 2-4 hrs of perfusion post-exchange, both eyes were perfusion-fixed with 8% PFA at 10 mmHg for 30 min. Whole globes were stored in 4% PFA for 2-4 days; then the corneo-scleral regions of the eyes were embedded in paraffin, sectioned and stained (hematoxylin and eosin) for histological examination.
Baseline outflow facility for control and drug-treated eyes was similar (1.6 ± 0.3 versus 1.8 ± 0.2 µl/min/mmHg). In drug-treated eyes, outflow facility was increased by 55 ± 9% (n=6, p < 0.01) over contralateral vehicle-treated eyes. Histological analysis showed no significant differences in tissue morphology or integrity between control and drug-treated eyes. Notably, results in our drug-treated calf eyes were comparable to the outflow facility increases observed in WEOP studies in mice (106%; Boussommier-Calleja 2012) and human (69%; Millard 2011) eyes.
Comparing the outflow facility measurements observed here to those from previous studies in mice and humans, we conclude that the PG-EP4 pharmacology of conventional outflow pathway in the calf eye is similar to both mice and humans to regulate IOP. These results demonstrate the utility of calf eyes in the whole-eye ex-vivo model to test other compounds expected to target the conventional outflow pathway.
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