Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide.
OBJECTIVE
To investigate long-term changes in the anterior segment of primate eyes treated for one year with different prostaglandin agonists and a prostamide. The results were compared with those obtained after vehicle treatment and in untreated controls.


METHODS
Sixteen young cynomolgus monkeys were unilaterally topically treated for 1 year with either bimatoprost 0.03% (prostamide), sulprostone 0.03% (EP(3)/EP(1) agonist), AH13205 0.1% (EP(2) agonist), or latanoprost 0.005% (FP agonist), which all lower IOP in this species at the doses applied. Four animals were treated with the vehicle only. In all cases the left eye was treated, the right eye remained untreated. Six monkeys served as untreated controls. Sections from 4 quadrants each of the circumference of the eyes of 16 drug-treated, 4 vehicle-treated and 6 untreated control animals were investigated qualitatively and quantitatively using light- and electronmicroscopy. The area of widened spaces between ciliary muscle bundles, the number of nerve fiber bundles at the muscle tips, and the width and length of the ciliary muscle were quantitated.


RESULTS
The general morphology of the ciliary muscle and trabecular meshwork was normal in appearance and shape in all animals, whereas some localized morphologic changes were observed in the drug-treated animals. The changes were found to be similar in all four treatment groups. In the ciliary muscle, there was a significant increase in optically empty spaces between muscle bundles in the anterior portion of the longitudinal and the reticular ciliary muscle compared with untreated and vehicle-treated control animals. Within these spaces, significantly more myelinated nerve fiber bundles were found in drug-treated compared with normal control animals. Ultrastructurally the spaces were partly covered by endothelial-like cells which, in some areas, were in contact with the basement membrane of the microvasculature. In all treatment groups, there were also changes in the trabecular meshwork region. Significant regional differences among the different quadrants of the eyes and quantitative differences between treatment groups were observed. The ciliary epithelium had a normal appearance in all treatment groups.


CONCLUSIONS
After one year of treatment with different prostaglandins and a prostamide, uveoscleral outflow pathways are enlarged and appear organized. Conventional outflow routes were also affected. Long-term treatment with AH13205, latanoprost, sulprostone, or bimatoprost also induces sprouting of nerve fibers.
D000287:Administration, Topical; D000577:Amides; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects* / Q000473:pathology*; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000069580:Bimatoprost; D002924:Ciliary Body / Q000187:drug effects / Q000294:innervation / Q000648:ultrastructure; D003008:Cloprostenol / Q000031:analogs & derivatives; D015232:Dinoprostone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008055:Lipids / Q000008:administration & dosage*; D008252:Macaca fascicularis; D009130:Muscle, Smooth / Q000294:innervation / Q000648:ultrastructure; D009412:Nerve Fibers / Q000648:ultrastructure; D009883:Ophthalmic Solutions; D017933:Peripheral Nervous System / Q000648:ultrastructure; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage*; D011466:Prostanoic Acids / Q000008:administration & dosage*; D014129:Trabecular Meshwork / Q000187:drug effects / Q000648:ultrastructure
D000577:Amides; D000959:Antihypertensive Agents; D008055:Lipids; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D011466:Prostanoic Acids; C081039:AH 13205; D003008:Cloprostenol; C016767:sulprostone; D000077338:Latanoprost; D015232:Dinoprostone; D000069580:Bimatoprost