Title:Molecular Damage in Glaucoma: from Anterior to Posterior Eye Segment. The MicroRNA Role
Volume: 4
Issue: 1
Author(s): Alberto Izzotti, Chiara Ceccaroli, Maria G. Longobardi, Rosanna T. Micale, Alessandra Pulliero, Sebastiano La Maestra and Sergio C. Sacca
Affiliation:
Keywords:
A kinase anchor protein 2, actin related protein 2/3 complex, aqueous humor proteins, IOP increase, microRNA,
Nestin, ONH damage, primary open angle glaucoma.
Abstract: Glaucoma targets a variety of different tissues located in both anterior (e.g., trabecular
meshwork) and posterior (e.g., optic nerve head) ocular segments. The transmission of damage between
these structures cannot be simply ascribed to intraocular pressure increase. Recent experimental
findings provide evidence for the involvement of molecular mediators including proteins and microRNAs.
Aqueous humor protein composition is characteristically altered during glaucoma progression.
Immunohistochemistry analyses indicate that proteins characterizing glaucomatous aqueous humor are
released by damaged trabecular meshwork. This feature incudes (a) Nestin, involved in stem cell recruitment and glial cell
activation; (b) A Kinase anchor protein, released as consequence of mitochondrial damage and Rho activation establishing
cell shape and motility; (c) Actin related protein 2/3 complex, involved in actin polymerization and cell shape maintenance.
As established both in vitro and in glaucomatous aqueous humor, trabecular meshwork cells damaged by oxidative
stress release extracellular microRNAs inducing glial cell activation, an established pathogenic mechanism in neurodegenerative
diseases. Released microRNAs include miR-21 (apoptosis), miR-450 (cell aging, maintenance of contractile
tone), miR-107 (Nestin expression, apoptosis), miR-149 (endothelia and extracellular matrix homeostasis). Experimental
evidences indicate that the uveoscleral pathway, via suprachoroidal space, can provide a potential route of access from the
anterior region to the posterior segment of the eye and could represent the path followed by biologic mediators to reach
the inner layer of the peripapillary retina and transmit damage signals from the anterior to posterior segment during glaucoma
course.
