Abstract
Optic nerve atrophy caused by abnormal intraocular pressure (IOP) remains the most common cause of irreversible loss of vision worldwide. The aim of this study was to determine whether topically applied IOP-lowering eye drugs affect retinal ganglion cells (RGCs) and retinal metabolism in a rat model of optic neuropathy. IOP was elevated through cauterization of episcleral veins, and then lowered either by the daily topical application of timolol, timolol/travoprost, timolol/dorzolamide, or timolol/brimonidine, or surgically with sectorial iridectomy. RGCs were retrogradely labeled 4 days prior to enucleation, and counted. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption ionization mass spectrometry, Western blotting, and immunohistochemistry allowed the identification of IOP-dependent proteomic changes. Genomic changes were scrutinized using microarrays and qRT-PCR. The significant increase in IOP induced by episcleral vein cauterization that persisted until 8 weeks of follow-up in control animals (p<0.05) was effectively lowered by the eye drops (p<0.05). As anticipated, the number of RGCs decreased significantly following 8 weeks of elevated IOP (p<0.05), while treatment with combination compounds markedly improved RGC survival (p<0.05). 2D-PAGE and Western blot analyses revealed an IOP-dependent expression of crystallin cry-βb2. Microarray and qRT-PCR analyses verified the results at the mRNA level. IHC demonstrated that crystallins were expressed mainly in the ganglion cell layer. The data suggest that IOP and either topically applied antiglaucomatous drugs influence crystallin expression within the retina. Neuronal crystallins are thus suitable biomarkers for monitoring the progression of neuropathy and evaluating any neuroprotective effects.
Highlights
Elevated intraocular pressure (IOP) is a major risk factor in glaucomatous optic neuropathy [1] for review and the mainstay of glaucoma treatment continues to be lowering of the IOP by pharmacological or surgical methods [2]
By 10–12 days after episcleral vein cauterization, the IOP had increased significantly by 1.6-fold to 24.861.7 mmHg (p,0.001). These values are consistent with those obtained by other groups, and are nearly identical to those recorded in humans, rabbits, and anesthetized monkeys [31]
Pharmacological hypotensive treatments are effective at lowering IOP and consistently affect retinal cell metabolism including the regulation of distinctive crystallins to below baseline levels
Summary
Elevated intraocular pressure (IOP) is a major risk factor in glaucomatous optic neuropathy [1] for review and the mainstay of glaucoma treatment continues to be lowering of the IOP by pharmacological or surgical methods [2]. Crystallins, which belong to the family of small heat shock proteins (HSPs) and comprise three major families (a, b, and c crystallins), have been found within RGCs [12,13]. Both neuroregenerative [13] and neurodegenerative [14] properties have been attributed to retinal crystallins. Crystallins may act as critical modulators in glaucoma and be integral to the process of glaucomatous neurodegeneration [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
