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. 2016 Oct 6;40(6):286-291.
doi: 10.1080/01658107.2016.1229339. eCollection 2016 Dec.

Histopathological Changes of Inner Retina, Optic Disc, and Optic Nerve in Rabbit with Advanced Retinitis Pigmentosa

Ken Asakawa  1 , Hitoshi Ishikawa  2 , Shigekazu Uga  2 , Kimiyo Mashimo  3 , Mineo Kondo  4 , Hiroko Terasaki  5
Affiliations

Histopathological Changes of Inner Retina, Optic Disc, and Optic Nerve in Rabbit with Advanced Retinitis Pigmentosa

Ken Asakawa et al. Neuroophthalmology. .

Abstract

We observed the histopathological changes of retinal ganglion cells (RGCs), optic disc, and optic nerve in rabbit with advanced retinitis pigmentosa (RP). Wild-type (WT) and rhodopsin transgenic (Tg) of RP rabbits were used at age 24 months. Light and electron microscopy were used to observe the retina, optic disc, and optic nerve. RGCs were also confirmed by immunofluorescent staining with a TUJ-1 monoclonal antibody. In addition to the rod and cone degeneration, we observed the astrocyte infiltration of the optic disc due to the damage of small RGCs and nerve fibres and atrophy of small optic nerve fibres. They subsequently lead to the optic disc excavation and atrophy of the optic nerve. Consequently, our histopathological study clarified that not only the outer retina but also the inner retina, the optic disc, and the optic nerve were also affected in the late stages of RP rabbit.

Keywords: Optic disc; optic nerve; rabbit; retinal ganglion cell; retinitis pigmentosa.

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Figures

Figure 1.
Figure 1.
Dissecting microscopy. (A) Compared with the Wild-type (WT) rabbit, (B) optic disc cupping, optic atrophy, and decreasing of nerve fibers (white arrow) are seen in the transgenic (Tg) rabbit.
Figure 2.
Figure 2.
Light microscopy. (A) The WT rabbit’s retina has a normal structure. (B) The Tg rabbit shows that rods and cones almost disappear. In the optic disc, (C) myelinated axons of the WT rabbit are densely crowded. (D) Those of the Tg rabbit are sparsely distributed, and the astrocyte infiltration are observed. In the optic nerve, (E) compared with the WT rabbit, (F) the interstitial spaces are enlarged. D = dorsal; V = ventral; N = nasal; T = temporal; ax = axon; as = astrocyte infiltration; is = interstitial spaces.
Figure 3.
Figure 3.
Electron microscopy. A) Rods and cones are clearly delineated in the WT rabbit. (B) Retinal pigment epithelium pigment granules irregularly distributed. Degeneration of cone nuclei, clump of mitochondria, and debris of outer segments are observed in the Tg rabbit. (C) Vacuolar degeneration of retinal ganglion cells (RGCs) and hypertrophic proliferation of Müller cells are observed. (D) Degeneration of myelinated axons in the optic disc. (E) Damage of the ring-like structure of the myelin sheath of small axons in the optic nerve. INL = inner nuclear layer; ONL = outer nuclear layer; R = rod; C = cone; cn = cone nuclei; m = mitochondria; os = outer segment; RGC = retinal ganglion cell; M = Müller cell; ms = myelin sheath.
Figure 4.
Figure 4.
TUJ-1 immunofluorescent staining of RGCs. (A) Large cells (white arrows) and small cells in the WT rabbit. (B) Some remaining RGCs have large cell bodies with long dendrites (white arrows), whereas the number of small cells has decreased in the Tg rabbit.
See this image and copyright information in PMC

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