TY - JOUR
T1 - Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models
AU - Bernstein, Steven L.
AU - Johnson, Mary A.
AU - Miller, Neil R.
N1 - Funding Information:
We thank Dr. Stanislav Tomarev (NEI) for his kind sharing of 35d IOP elevation microarray data, and Dr. John Morrison (Casey Eye Center, Oregon) for the use of his vascular figure of the rat optic nerve, and Dr. Len Levin, for his kind contribution of clinical material from an individual who died 28 days post-NAION. We also gratefully acknowledge the work of many of our postdoctoral fellows and students, in particular Dr Nitza Goldenberg-Cohen, Celia Chen, Charles Zhang and James Nicholson. The technical assistance of Yan Guo and Theresa Alexander are also greatly appreciated. This work was supported by a grant from the Rasmussen Foundation , Donner Foundation , and NIH grants RO1-EY015304 and RO1EY19529 from the National Eye Institute . Their support is gratefully acknowledged.
PY - 2011/5
Y1 - 2011/5
N2 - Anterior ischemic optic neuropathy (AION) can be divided into nonarteritic (NAION) and arteritic (AAION) forms. NAION makes up ~85% of all cases of AION, and until recently was poorly understood. There is no treatment for NAION, and its initiating causes are poorly understood, in part 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, and the power of a 'vertically integrated' multi-species approach can 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 that seen in clinical disease, including sectoral axonal involvement, and in-vivo electrophysiological data from these models are consistent with clinical data. Early post-infarct events reveal an unexpected inflammatory response, and changes in intraretinal gene expression for both stress response, while sparing outer retinal function, which occurs in AAION models. Histologically, the NAION models reveal an isolated loss of retinal ganglion cells by apoptosis. There are changes detectable by immunohistochemistry suggesting 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.
AB - Anterior ischemic optic neuropathy (AION) can be divided into nonarteritic (NAION) and arteritic (AAION) forms. NAION makes up ~85% of all cases of AION, and until recently was poorly understood. There is no treatment for NAION, and its initiating causes are poorly understood, in part 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, and the power of a 'vertically integrated' multi-species approach can 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 that seen in clinical disease, including sectoral axonal involvement, and in-vivo electrophysiological data from these models are consistent with clinical data. Early post-infarct events reveal an unexpected inflammatory response, and changes in intraretinal gene expression for both stress response, while sparing outer retinal function, which occurs in AAION models. Histologically, the NAION models reveal an isolated loss of retinal ganglion cells by apoptosis. There are changes detectable by immunohistochemistry suggesting 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.
KW - Arteritic anterior ischemic optic neuropathy
KW - Axonal ischemia
KW - Inflammation
KW - Ischemic optic neuropathy
KW - Nonarteritic anterior ischemic optic neuropathy
KW - Optic nerve
KW - Optic nerve electrophysiology
KW - Optic nerve gene expression
KW - Retinal ganglion cell
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U2 - 10.1016/j.preteyeres.2011.02.003
DO - 10.1016/j.preteyeres.2011.02.003
M3 - Article
C2 - 21376134
AN - SCOPUS:79954644136
SN - 1350-9462
VL - 30
SP - 167
EP - 187
JO - Progress in Retinal and Eye Research
JF - Progress in Retinal and Eye Research
IS - 3
ER -