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Dorzolamide Reduces the Damaging Influence of Ischemia/Reperfusion to the Rat Retina
1Schmidt K.-G., 2Chidlow G., 2Wood J., 2Osborne N., 1Pillunat L. E.,
1Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde (Dresden)
2Nuffield Laboratory of Ophthalmology, University of Oxford, Cytoprotection (Oxford)
Purpose: Dorzolamide is a carbonic anhydrase inhibitor used to reduce intraocular pressure (IOP) which is also suggested to improve perfusion to the optic nerve head. The aim of this study was to determine whether dorzolamide counteracts the effects of ischemia/reperfusion (IR) to the rat retina.
Methods: Rats received either dorzolamide or vehicle in standard dosage (BID, 1 eye), for 5 days before and 8 days after ischaemia (raising the IOP to 120 mmHg for 45 min). The electroretinogram (ERG) was recorded before and 5 days after ischemia. Rats were killed 5 or 8 days after IR and the retinas processed for immuohistochemistry and for the determination of mRNA levels of Thy-1, neurofilament light (NF-L), rhodopsin, and the housekeeping gene (glyceraldehyde 3-phosphate dehydrogenase, G3PDH) by RT-PCR, respectively.
Results: IR caused a significant reduction of the b- (79%) and a- (52%) wave amplitudes of the ERG in vehicle-treated rats (n=8). In animals treated with dorzolamide, the reductions of the b- and a-wave amplitudes were only 49% and 31%, respectively (n=8). The differences between the two groups of animals were statistically significant. Immunohistochemical data partially reflected these findings, where it was concluded that the decreases observed in the Thy-1 (located to ganglion cells) and choline acetyltransferase immunoreactivities induced by IR were less evident in the dorzolamide-treated animals. Moreover, in vehicle-treated rats, there was a significant reduction in retinal levels of Thy-1 and NF-L mRNAs relative to those of G3PDH in eyes subjected to IR when compared with control eyes (n=8). However, the decreases in Thy-1 and NF-L mRNAs were not apparent in the ischemic eyes of dorzolamide treated rats.
Conclusions: Topically applied dorzolamide attenuates the effect of IR in the retina.