Direct and indirect approaches to neuroprotective therapy of glaucomatous optic neuropathy.

Leonard Levin // Publications // Jun 01 1999

PubMed ID: 10416753

Author(s): Levin LA. Direct and indirect approaches to neuroprotective therapy of glaucomatous optic neuropathy. Surv Ophthalmol. 1999 Jun;43 Suppl 1:S98-101. Review. PMID 10416753

Journal: Survey Of Ophthalmology, Volume 43 Suppl 1, Jun 1999

Retinal ganglion cell death is the final common pathway of virtually all diseases of the optic nerve, including glaucomatous optic neuropathy. In recent years it has been shown that retinal ganglion cells die after axonal injury via a programmed cell death process called apoptosis. The dynamics of retinal ganglion cell death reflect the timing and degree of the axonal injury, rather than its nature. For example, whether mediated by ischemia (corresponding to abnormalities of peripapillary circulation) or compression (e.g., changes in retrograde transport caused by increased intraocular pressure), the end result is a series of changes at the level of the axon, which subsequently affect the retinal ganglion cell body. Our studies on neuroprotection of retinal ganglion cells have focused on general mechanisms applicable to axonal injuries. By dissecting the pathways by which retinal ganglion cells die in these situations, strategies for protection may become manifest. We and others have found that production of certain reactive oxygen species is a necessary step for neuronal death after neurotrophin deprivation. In response, cells invoke compensatory mechanisms to maintain survival in the face of this attack. We have studied the transcriptional regulation of one candidate compensatory gene and discuss it as a model for gene-based approaches to neuroprotective therapy for glaucomatous optic neuropathy. By approaching the problem of therapy from this point of view, it may become possible to prevent irreversible glaucomatous optic nerve changes by inducing endogenous cell-rescue mechanisms and, thus, with the retinal ganglion cells’ own defense mechanisms, to prevent its death.