May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Molecular and Cellular Changes Associated With Experimental Glaucoma in Monkey – A Case Report
Author Affiliations & Notes
  • P. Schmid
    Disease Area Ophthalmology, Novartis Inst Biomed Res, Basel, Switzerland
  • A. Doelemeyer
    Disease Area Ophthalmology, Novartis Inst Biomed Res, Basel, Switzerland
  • A. Quadri
    Disease Area Ophthalmology, Novartis Inst Biomed Res, Basel, Switzerland
  • J. Kremers
    Disease Area Ophthalmology, Novartis Inst Biomed Res, Basel, Switzerland
  • C. Lambert
    Disease Area Ophthalmology, Novartis Inst Biomed Res, Basel, Switzerland
  • G. Lambrou
    Disease Area Ophthalmology, Novartis Inst Biomed Res, Basel, Switzerland
  • Footnotes
    Commercial Relationships  P. Schmid, Novartis Ltd. E; A. Doelemeyer, Novartis Ltd. E; A. Quadri, Novartis Ltd. E; J. Kremers, Novartis Ltd E; C. Lambert, Novartis Ltd E; G. Lambrou, Novartis Ltd E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 2218. doi:
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      P. Schmid, A. Doelemeyer, A. Quadri, J. Kremers, C. Lambert, G. Lambrou; Molecular and Cellular Changes Associated With Experimental Glaucoma in Monkey – A Case Report . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2218.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: To characterize pathomechanisms of optic nerve damage and neurodegeneration in an experimental monkey glaucoma model. Methods: Argon laser treatment of the anterior chamber angle was used to induce chronic ocular hypertension in the right eye of a cynomolgous monkey. Euthanasia was performed five months after laser treatment. Both eyes were enucleated for immunohistochemical investigations using antibody markers for apoptosis (cleaved caspase–3), connective tissue remodeling (TGF–ß type II receptor and fibronectin), vascularisation (CD31), amyloid deposition (Aß and ubiquitin), and macrophage/microglia activation (CD68). Results: Glaucomatous damage of the optic nerve (ON) head in response to stable IOP elevation (>40mmHg) after laser treatment was evidenced by fundus examinations and confocal laser tomography. Unilateral glaucoma was confirmed by histology, which revealed optic nerve head excavation and focal retinal ganglion cell loss in the lasered eye, but not in the healthy eye. Cleaved caspase–3 positive apoptotic cells were identified in the ganglion cell layer of the glaucomatous eye, although the healthy fellow eye revealed no signs of cell death. In the diseased eye an almost complete interruption of optic nerve fibers was visible in peripheral parts of the lamina cribrosa. These areas showed a high density of CD31 positive blood vessels, and increased staining of TGF–ß receptor and fibronectin in adjacent lamina fibroblasts. Most notably, the degenerating axons distal to the altered lamina exhibited depositions, which stained positive for beta amyloid and ubiquitin. Such deposits were also found within CD68 positive macrophage/microglia cells, which accumulated at sites of axonal degeneration. Conclusions: The present findings suggest that ON damage induced by severe ocular hypertension initiates tissue repair reactions in the lamina cribrosa, as indicated by markers of fibroblast activation, altered matrix synthesis and angiogenesis. Subsequent fibrotic alterations in the lamina may contribute to progressive axonal injury and nerve fiber degeneration. The observed accumulation of macrophages/microglia cells, predominantly at sites of amyloid deposition, suggests that degenerating axons release abnormally processed or misfolded proteins, which provoke an inflammatory response. Consequently, chronic fibrotic and/or inflammatory processes in the ON may promote secondary neurodegenerative processes in glaucoma.

Keywords: extracellular matrix • pathology: experimental • microglia 
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