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

Takashi Fujishiro,Hiroshi Kawasaki,Reiko Yamagishi,Ryo Asaoka,Megumi Honjo,Makoto Aihara

doi:10.3390/ijms21041339

Abstract

We investigated structural changes and astrocyte responses of the lateral geniculate nucleus (LGN) in a ferret model of ocular hypertension (OH). In 10 ferrets, OH was induced via the injection of cultured conjunctival cells into the anterior chamber of the right eye; six normal ferrets were used as controls. Anterograde axonal tracing with cholera toxin B revealed that atrophic damage was evident in the LGN layers receiving projections from OH eyes. Immunohistochemical analysis with antibodies against NeuN, glial fibrillary acidic protein (GFAP), and Iba-1 was performed to specifically label neurons, astrocytes, and microglia in the LGN. Significantly decreased NeuN immunoreactivity and increased GFAP and Iba-1 immunoreactivities were observed in the LGN layers receiving projections from OH eyes. Interestingly, the changes in the immunoreactivities were significantly different among the LGN layers. The C layers showed more severe damage than the A and A1 layers. Secondary degenerative changes in the LGN were also observed, including neuronal damage and astrocyte reactions in each LGN layer. These results suggest that our ferret model of OH is valuable for investigating damages during the retina–brain transmission of the visual pathway in glaucoma. The vulnerability of the C layers was revealed for the first time.

Highlights

Glaucoma is a leading cause of irreversible blindness worldwide, and it is characterized by the death of retinal ganglion cells [1,2]
Ferrets have abundant non-cross fibers in the optic nerve, unlike mice and rats, and the C layer projected from W cells is observed as independent layers
We examined glaucomatous optic neuropathy and associated central neuropathy in the lateral geniculate nucleus (LGN) using a ferret model of ocular hypertension (OH)

Summary

Introduction

Glaucoma is a leading cause of irreversible blindness worldwide, and it is characterized by the death of retinal ganglion cells [1,2]. Glaucoma optic neuropathy (GON) leads to secondary damage to the central visual system, which processes vision via the optic nerve, the lateral geniculate nucleus (LGN), and the primary visual cortex (V1) [3,4,5,6]. In experimentally induced glaucoma in monkeys, neuronal degeneration was observed in the magnocellular, parvocellular, and koniocellular pathways in the LGN, and these changes were related to the increase in intraocular pressure (IOP) and severity of optic nerve damage [7,8]. These secondary degenerations in the central nervous system may indicate that GON is a complicated, irreversible, and progressive disease. 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]

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