Gene Therapeutical Approaches in Primary Open Angle Glaucoma

Hudde T.,
Universität-Gesamthochschule Essen, Zentrum für Augenheilkunde (Essen)

Somatic gene transfer represents an attractive approach for the treatment of eye diseases. Easy surgical access to all tissues of the eye, visibility of the induced effects and low risk of systemic infection may be part of the reason. Numerous basic research presentations deal with gene therapy for chronic open angle glaucoma. Increased aqueous outflow facility by modification of the extracellular matrix of trabecular meshwork is intended by transfer of matrix metalloproteinases, and inactivation of their inhibitors, respectively. Transfer of dominant-negative RhoA results in decreased intraocular pressure probably by reduction of intercellular attachments in Schlemm’s canal cells together with a relaxation of infected trabecular meshwork cells in a human perfusion model. SPARC (osteonectin/secreted protein acidic and rich in cysteine) induces cell adhesion and cell morphology changes in confluent monolayers of human trabecular meshwork cells. Decreased cell volume caused by transfer of genes encoding for ion channels in the cell membrane might as well reduce intraocular pressure. Neuroprotective strategies aim at a reduction of apoptotic axon loss of the optic nerve for example by the capase inhibitor BIRC4 (human baculoviral IAP repeat-containing protein-4) as demonstrated in a rat model of glaucoma. Although clinical application is not imminent the results so far are promising.

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