Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models

Anterior ischemic optic neuropathy (AION) can be divided into nonarteritic (NAION) and arteritic (AAION) forms. NAION makes up similar to 85% of all cases of AION. There is no treatment for NAION, and its initiating causes are poorly understood, partly because NAION is not lethal, making it difficult to obtain fresh, newly affected tissue for study. In-vivo electrophysiology and post-mortem studies reveal specific responses that are associated with NAION. New models of NAION have been developed which enable insights into the pathophysiological events surrounding this disease. These models include both rodent and primate species, enabling a 'vertically integrated' multi-species approach to help in understanding the common cellular mechanisms and physiological responses to clinical NAION, and to identify potential approaches to treatment. The models utilize laser light to activate intravascular photoactive dye to induce capillary vascular thrombosis, while sparing the larger vessels. The observable optic nerve changes associated with rodent models of AION (rAION) and primate NAION (pNAION) are indistinguishable from those seen in clinical disease, including sectoral axonal involvement. In-vivo electro-physiological data from these models are consistent with clinical data. Early post-infarct analysis reveals an unexpected inflammatory response, and changes in intraretinal stress response gene expression, sparing of outer retinal function, which occurs in AAION models. Histologically, the NAION models produce an isolated loss of retinal ganglion cells by apoptosis. Changes detectable by immunohistochemistry suggest that other retinal cells mount a brisk response to retinal ganglion cell distress without themselves dying. The optic nerve ultimately shows axonal loss and scarring. Inflammation is a prominent early histological feature. This suggests that clinically, specific modulation of inflammation may be a useful approach to NAION treatment early in the course of the disease. (C) 2011 Published by Elsevier Ltd.