Establishment of an experimental ferret ocular hypertension model for the analysis of central visual pathway damage

Abstract

Glaucoma optic neuropathy (GON) is a condition where pathogenic intraocular pressure (IOP) results in axonal damage following retinal ganglion cell (RGC) death, and further results in secondary damage of the lateral geniculate nucleus (LGN). Therapeutic targets for glaucoma thus focus on both the LGN and RGC. However, the temporal and spatial patterns of degeneration and the mechanism of LGN damage have not been fully elucidated. Suitable and convenient ocular hypertension (OH) animal models with binocular vision comparable to that of monkeys are strongly needed. The ferret is relatively small mammal with binocular vision like humans – here we report on its suitability for investigating LGN. We developed a new method to elevate IOP by injection of cultured conjunctival cells into the anterior chamber to obstruct aqueous outflow. Histologically, cultured conjunctival cells successfully proliferated to occlude the angle, and IOP was elevated for 13 weeks after injection. Macroscopically, the size of the eye gradually expanded. Subsequent enlargement of optic nerve head cupping and atrophic damage of LGN projected from the OH eye were clearly observed by anterograde staining with cholera toxin B. We believe the ferret may be a promising OH model to investigate secondary degeneration of central nervous system including LGN.

Assessment of retinal ganglion cell damage in glaucomatous optic neuropathy: Axon transport, injury and soma loss

“…Application of CTB fluorescent conjugates clearly labels individual RGC axons regardless of transport direction (Dengler-Crish et al, 2014, Fig. 1D, E and H), and have been used in studies of axonal regrowth in the ON (Liu et al, 2009;Sun et al, 2011;Yang and Cho, 2005) and transport disruption in experimental GON Chidlow et al, 2011;Dengler-Crish et al, 2014;Formichella et al, 2014;Fujishiro et al, 2014;Lambert et al, 2011;Ward et al, 2014).…”

Structural Changes and Astrocyte Response of the Lateral Geniculate Nucleus in a Ferret Model of Ocular Hypertension

“…In our ferret model of OH, damage to the optic tract projected from the OH eye was apparent and damage to the optic tract of the untreated eye was also significant [26]. Thus, secondary degeneration of the optic tract accompanied by the degeneration of the glaucomatous optic nerve may be investigated in this ferret model.…”

“…The right eyes of 10 ferrets were established as OH eyes (G1) by injecting cultured conjunctival cells into the anterior chamber aiming the angle closure synechia [26], and the contralateral left eyes were untreated and used as a control against the right OH eye (G2). Twelve eyes of 6 ferrets with normal ocular pressure were used as controls (G3).…”

“…However, performing numerous experiments in monkeys is significantly challenging. Thus, we have previously reported on the development of a ferret model of ocular hypertension (OH) [26]. Ferrets possess highly developed binocular vision compared with rodents, and electrophysiological and morphological data of the ferret visual system have been accumulated [27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”

Selective Early Glial Reactivity in the Visual Pathway Precedes Axonal Loss, Following Short-Term Cerebrospinal Fluid Pressure Reduction

“…To detect the connection and degeneration of the visual system from the eye to the LGN and SC, dyes were injected as previously described. 20,35 In brief, 2 ll of freshly prepared 3% rhodamine-b-isothiocyanate (RITC) was injected intravitreally with a 28-gauge needle at the pars plana of each right eye. The brains were removed 3 days after injection.…”