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Focus on molecular events in the anterior chamber leading to glaucoma

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Abstract

Primary open-angle glaucoma is a multifactorial disease that affects the retinal ganglion cells, but currently its therapy is to lower the eye pressure. This indicates a definite involvement of the trabecular meshwork, key region in the pathogenesis of glaucoma. This is the first target of glaucoma, and its functional complexity is a real challenge to search. Its functions are those to allow the outflow of aqueous humor and not the reflux. This article describes the morphological and functional changes that happen in anterior chamber. The “primus movens” is oxidative stress that affects trabecular meshwork, particularly its endothelial cells. In these develops a real mitochondriopaty. This leads to functional impotence, the trabecular meshwork altering both motility and cytoarchitecture. Its cells die by apoptosis, losing barrier functions and altering the aqueous humor outflow. All the morphological alterations occur that can be observed under a microscope. Intraocular pressure rises and the malfunctioning trabecular meshwork endotelial cells express proteins that completely alter the aqueous humor. This is a liquid whose functional proteomics complies with the conditions of the trabecular meshwork. Indeed, in glaucoma, it is possible detect the presence of proteins which testify to what occurs in the anterior chamber. There are six classes of proteins which confirm the vascular endothelium nature of the anterior chamber and are the result of the morphofunctional trabecular meshwork decay. It is possible that, all or in part, these proteins can be used as a signal to the posterior pole.

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Abbreviations

8-OHdg:

8-Hydroxydeoxyguanosine

AC:

Anterior chamber

AF:

Actin microfilaments

AH:

Aqueous humor

ECM:

Extracellular matrix

ELAM-1:

Endothelial leukocyte adhesion molecule-1

GSH:

Reduced glutathione

IF:

Intermediate filaments

IL:

Interleukin

JCT:

Juxtacanalicular connective tissue

MT:

Microtubules

mtDNA:

Mitochondrial DNA

NO:

Nitric oxide

ONH:

Optic nerve head

POAG:

Primary open-angle glaucoma

RGCs:

Retinal ganglion cells

RNFL:

Retinal nerve fibre layer

ROS:

Reactive oxygen species

SCS:

Suprachoroidal space

SOD:

Superoxide dismutase

TM:

Trabecular meshwork

UV:

Ultra violet radiation

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Acknowledgment

This study was supported by the US Glaucoma Research Foundation (TGF) (New York, USA).

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  1. Ophthalmology Unit, Department of Head and Neck Pathologies, St Martino Hospital, Viale Benedetto XV, 16132, Genoa, Italy

    Sergio Claudio Saccà

  2. Section of Hygiene and Preventive Medicine, Department of Health Sciences, University of Genoa, Genoa, Italy

    Alberto Izzotti

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  1. Sergio Claudio Saccà
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  2. Alberto Izzotti
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Correspondence to Sergio Claudio Saccà.

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Saccà, S.C., Izzotti, A. Focus on molecular events in the anterior chamber leading to glaucoma. Cell. Mol. Life Sci. 71, 2197–2218 (2014). https://doi.org/10.1007/s00018-013-1493-z

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  • DOI: https://doi.org/10.1007/s00018-013-1493-z

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