The non-human primate experimental glaucoma model

Abstract

The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic IOP elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model.

The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change

“…Our findings suggest that the parameter post-BMO total prelaminar volume 7 is important in glaucoma because it quantifies overall laminar/ scleral deformation by capturing three of these components (laminar deformation, anterior scleral canal expansion, and anterior laminar insertion migration) in a single parameter that may eventually be measurable using SDOCT. 16,17,27 Experimental glaucoma versus control eye differences in post-BMO total prelaminar volume ranged from 36% to 578% in the 21 EG eyes and were progressive, by which we mean there Fig. 2).…”

“…These studies preceded our implementation of spectraldomain optical coherence tomography (SDOCT), 25,26 thus OCT ONH rim and retinal nerve fiber layer thickness (RFNLT) measurements were not obtained. After three to eight baseline testing sessions, one eye of each monkey was given laser-induced, chronic experimental IOP elevation, 27 and IOP 10 mm Hg imaging of both eyes of each animal was repeated at 2-week intervals until euthanization occurred. Animals were euthanized at varying levels of CSLT progression extending from early (onset confirmed twice) through endstage (progression that halted in the face of prolonged IOP elevation) CSLT MPD change from baseline.…”

“…[6][7][8][9]27 For this study, both eyes of 12 animals were reconstructed at a voxel resolution of 1.5 3 1.5 3 1.5 lm. Briefly, the ONH and peripapillary sclera were trephined (6-mm diameter), embedded in paraffin, and mounted on a microtome with the ONH surface facing out.…”

In Vivo Imaging of the Retina, Choroid, and Optic Nerve Head in Guinea Pigs

“…Non-human primate models, though having a close resemblance to human anatomy and cellular organization, have limitations in terms of economics and practicality. 35 Current rodent models provide an opportunity to study genetic manipulations and test large numbers of animals, but are limited by their small globe size and structural differences in the ONH compared to humans, 33 primarily the absence of a collagenous lamina cribrosa. 36, 37 Structural changes in the lamina cribrosa have been described in glaucomatous eyes in a number of previous studies.…”

Modeling Human Glaucoma: Lessons from the in vitro Models

“…episcleral vein cauterization, episcleral vein ligation, laser photocoagulation of the limbar tissues, injection of hypertonic saline in the episcleral veins, and injection of microbeads in the anterior chamber) [for a revision of the animal models, see [9][10][11]. Many species have been used, including nonhuman primates which may better resemble the human anatomy and cellular response [12] . However, due to practical and economic reasons, rodents have been the most studied.…”