Structural and functional effects of hemiretinal endodiathermy axotomy in cynomolgus macaques

• Published in: Investigative ophthalmology & visual science Vol. 54; no. 5; pp. 3479 - 3492
• Main Authors: Dashek, Ryan J, Kim, Charlene B Y, Rasmussen, Carol A, Hennes-Beean, Elizabeth A, Ver Hoeve, James N, Nork, T Michael
• Format: Journal Article
• Language: English
• Published: United States The Association for Research in Vision and Ophthalmology 17.05.2013
• Subjects: Animals; Axotomy; Choroid - blood supply; Disease Models, Animal; Electrocoagulation; Electroretinography; Female; Fluorescein Angiography; Glial Fibrillary Acidic Protein - metabolism; Immunohistochemistry; Macaca fascicularis; Male; Nerve Fibers - pathology; Opsins - metabolism; Photoreceptor Cells, Vertebrate - metabolism; Photoreceptor Cells, Vertebrate - pathology; Retina - physiology; Retinal Degeneration - physiopathology; Retinal Ganglion Cells - pathology; Retinal Vessels - physiology; Rhodopsin - metabolism; Tomography, Optical Coherence; photoreceptor morphology; choroidal blood flow; optical coherence tomography; multifocal electroretinography; endodiathermy axotomy
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.12-11265

Outer retinal injury has been well described in glaucoma. To better understand the source of this injury, we wanted to develop a reliable model of partial retinal ganglion cell (RGC) axotomy. Endodiathermy spots were placed along the inferior 180° adjacent to the optic nerve margin in the right eyes of four cynomolgus monkeys. Fluorescein angiography, spectral domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG) were performed at various intervals. Two animals were sacrificed at 3 months. Two animals were sacrificed at 4 months, at which time they underwent an injection of fluorescent microspheres to measure regional choroidal blood flow. Retinal immunohistochemistry for glial fibrillary acidic protein (GFAP), rhodopsin, S-cone opsin, and M/L-cone opsin were performed, as were axon counts of the optic nerves. At 3 months, there was marked thinning of the inferior nerve fiber layer on SD-OCT. The mfERG waveforms were consistent with inner but not outer retinal injury. Greater than 95% reduction in axons was seen in the inferior optic nerves but no secondary degeneration superiorly. There was marked thinning of the nerve fiber and ganglion cell layers in the inferior retinas. However, the photoreceptor histology was similar in the axotomized and nonaxotomized areas. Regional choroidal blood flow was not affected by the axotomy. Unlike experimental glaucoma, hemiretinal endodiathermy axotomy (HEA) of the RGCs produces no apparent anatomic, functional, or blood flow effects on the outer retina and choroid.