Regulation of retinal proteome by topical antiglaucomatous eye drops in an inherited glaucoma rat model.
Examination of the response of the retinal proteome to elevated intraocular pressure (IOP) and to the pharmacological normalization of IOP is crucial, in order to develop drugs with neuroptorective potential. We used a hereditary rat model of ocular hypertension to lower IOP with travaprost and dorzolamide applied topically on the eye surface, and examine changes of the retinal proteome. Our data demonstrate that elevated IOP causes alterations in the retinal protein profile, in particular in high-mobility-group-protein B1 (HMGB1), calmodulin, heat-shock-protein (HSP) 70 and carbonic anhydrase II expression. The changes of the retinal proteome by dorzolamide or travoprost are different and independent of the IOP lowering effect. This fact suggests that the eye drops exert a direct IOP-independent effect on retinal metabolism. Further investigations are required to elucidate the potential neuroprotective mechanisms signaled through changes of HMGB1, calmodulin, HSP70 and carbonic anhydrase II expression in glaucoma. The data may facilitate development of eye drops that exert neuroprotection through direct pharmacological effect.
Institute of Experimental Ophthalmology, School of Medicine, University Clinics Münster and Interdisciplinary Centre for Clinical Research (IZKF), Münster, Germany.
Maurice
M
Schallenberg
Verena
V
Prokosch
Solon
S
Thanos
D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D003008:Cloprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005901:Glaucoma / Q000188:drug therapy / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects; D009883:Ophthalmic Solutions; D010449:Peptide Mapping; D020543:Proteome / Q000187:drug effects / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D000069557:Travoprost
D002147:Calmodulin; D024243:HMGB1 Protein; D018840:HSP70 Heat-Shock Proteins; D009883:Ophthalmic Solutions; D020543:Proteome; D013449:Sulfonamides; D013876:Thiophenes; D003008:Cloprostenol; C062765:dorzolamide; D024402:Carbonic Anhydrase II; D000069557:Travoprost