4.6 Article

Structural and Functional Effects of Hemiretinal Endodiathermy Axotomy in Cynomolgus Macaques

Journal

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 54, Issue 5, Pages 3479-3492

Publisher

ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.12-11265

Keywords

endodiathermy axotomy; choroidal blood flow; photoreceptor morphology; multifocal electroretinography; optical coherence tomography

Categories

Funding

  1. National Institutes of Health [P30 EY016665, R01 EY014041]
  2. BrightFocus Foundation
  3. Research to Prevent Blindness
  4. Wisconsin National Primate Research Center [P51RR000167, P51OD011106]

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PURPOSE. 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. METHODS. Endodiathermy spots were placed along the inferior 180 degrees 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. RESULTS. 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. CONCLUSIONS. 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.

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