Management options for visual pathway compression from optic gliomas.

Optic pathway gliomas (OPGs) manifest with neuro-ophthalmic symptoms and signs; however, presentation can vary as their location and growth patterns are highly variable. An exophytic expansion of an OPG within the intracranial cavity can cause compression on neurological structures, warranting intervention. However, management guidelines are limited and the treatment itself may also cause neuro-ophthalmic complications. Therefore, clinical decision-making must include input from a multidisciplinary team that includes ophthalmology, neurosurgery, radiation oncology and neuroradiology.

Role of the c-Jun N-terminal kinase pathway in retinal excitotoxicity, and neuroprotection by its inhibition.

Retinal excitotoxicity is associated with retinal ischemia, and with glaucomatous and traumatic optic neuropathy. The present study investigates the role of c-Jun N-terminal kinase (JNK) activation in NMDA-mediated retinal excitotoxicity and determines whether neuroprotection can be obtained with the JNK pathway inhibitor, D-form of JNK-inhibitor 1 (D-JNKI-1). Young adult rats received intravitreal injections of 20 nmol NMDA, which caused extensive neuronal death in the inner nuclear and ganglion cell layers. This excitotoxicity was associated with strong activation of calpain, as revealed by fodrin cleavage, and of JNK. The cell-permeable peptide D-JNKI-1 was used to inhibit JNK. Within 40 min of its intravitreal injection, FITC-labeled D-JNKI-1 spread through the retinal ganglion cell layer into the inner nuclear layer and interfered with the NMDA-induced phosphorylation of JNK. Injections of unlabeled D-JNKI-1 gave unprecedentedly strong neuroprotection against cell death in both layers, lasting for at least 10 days. The NMDA-induced calpain-specific fodrin cleavage was likewise strongly inhibited by D-JNKI-1. Moreover the electroretinogram was partially preserved by D-JNKI-1. Thus, the JNK pathway is involved in NMDA-mediated retinal excitotoxicity and JNK inhibition by D-JNKI-1 provides strong neuroprotection as shown morphologically, biochemically and physiologically.

Neuroprotection for optic nerve disorders.

PURPOSE OF REVIEW: The concept that optic nerve fiber loss might be reduced by neuroprotection arose in the mid 1990s. The subsequent research effort, focused mainly on rodent models, has not yet transformed into a successful clinical trial, but provides mechanistic understanding of retinal ganglion cell death and points to potential therapeutic strategies. This review highlights advances made over the last year. RECENT FINDINGS: In excitotoxicity and axotomy models retinal ganglion cell death has been shown to result from a complex interaction between retinal neurons and Müller glia, which release toxic molecules including tumor necrosis factor alpha. This counteracts neuroprotection by neurotrophins such as nerve growth factor, which bind to p75NTR receptors on Müller glia stimulating the toxic release. Another negative effect against neurotrophin-mediated protection involves the action of LINGO-1 at trkB brain-derived neurotrophic factor (BDNF) receptors, and BDNF neuroprotection is enhanced by an antagonist to LINGO-1. As an alternative to pharmacotherapy, retinal defences can be stimulated by exposure to infrared radiation. SUMMARY: The mechanisms involved in glaucoma and other optic nerve disorders are being clarified in rodent models, focusing on retrograde degeneration following axonal damage, excitotoxicity and inflammatory/autoimmune mechanisms. Neuroprotective strategies are being refined in the light of the mechanistic understanding.