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Up-regulation of semaphorin expression in retina of glaucomatous rabbits

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Abstract

Background

Glaucoma is a term encompassing a variety of diseases that end in the death of retinal ganglion cells (RGC). Although a variety of factors can initiate the disease onset, increased intraocular pressure (IOP) is one of the major risk factors. In our previous study we found that semaphorins were causally involved in RGC death following axotomy. Since a common feature of all retinal neuropathies is axonal damage, we hypothesized that semaphorins are involved in glaucoma-induced RGC death. The purpose of this study was to analyze the effect of increased IOP on RGC viability and to analyze semaphorin expression pattern in glaucomatous retinas.

Methods

Utilizing retrograde-labeled dye (4-Di-10-Asp) and hematoxylin-eosin staining, we investigated the effect of elevated levels of IOP on RGC viability. In addition, immunohistochemical analysis and western blotting were used to study the pattern of semaphorin expression in retinas of rabbits with genetically developed increased IOP and subsequently glaucoma.

Results

Using specific anti-semaphorin antibodies, the expression of a single protein with the size of a semaphorin protein, 110 kDa, was detected; its expression was up-regulated in glaucomatous rabbits compared with controls. Time-course analysis revealed that semaphorin expression peaked between 2 and 6 months of age and declined thereafter. Immunohistochemical analysis revealed that semaphorin expression was up-regulated specifically in the ganglion cell layer, which is a structure that is highly affected in glaucoma.

Conclusion

Deciphering the molecular mechanisms of glaucoma-induced death and its mediators is a crucial step towards designing new therapeutic strategies to treat this incurable disease.

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Acknowledgements

This work was supported in part by grants from the Israeli Ministry of Health (to A.B.) and the Stein Research Fund (to A.S.S.).

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Authors and Affiliations

  1. Goldchleger Eye Research Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arieh S. Solomon

  2. Sackler Faculty of Medicine, Tel Aviv University, Israel

    Arieh S. Solomon, Michal Kimron, Vered Holdengreber, Anat Nizan, Anat Shirvan & Ari Barzilai

  3. Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978, Tel Aviv , Israel

    Michal Kimron, Anat Nizan & Ari Barzilai

  4. Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Vered Holdengreber

  5. Alec and Myra Marmot Hybridoma Laboratory, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Margalit Yaakobowicz, Ella Harness & Nechama I. Smorodinsky

  6. Department of Neurology and Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel

    Anat Shirvan

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  1. Arieh S. Solomon
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Correspondence to Ari Barzilai.

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Solomon, A.S., Kimron, M., Holdengreber, V. et al. Up-regulation of semaphorin expression in retina of glaucomatous rabbits. Graefe's Arch Clin Exp Ophthalmol 241, 673–681 (2003). https://doi.org/10.1007/s00417-003-0684-y

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  • DOI: https://doi.org/10.1007/s00417-003-0684-y

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