Ординатура / Офтальмология / Английские материалы / Eye, Retina, and Visual System of the Mouse_Chalupa, Williams_2008

Plate 32 Melanosomes contribute to DBA/2J pigment dispersion. A–D, Mutations in genes encoding the melanosomal proteins TYRP1 and GPNMB cause iris disease. DBA/2J mice that are homozygous mutant for both genes have the most severe disease (D). All images are from 24-month-old mice. E, Evidence of an immune contribution to DBA/2J pigment dispersion. Bone marrow genotype has an important effect on the phenotype. (See

figure 39.1.) (Modified from John, 2005. A–D, Reproduced from Mo et al., 2003 [ Journal of Experimental Medicine, 2003, 197:1335– 1344. Copyright 2003, Rockefeller University Press]. E, Reproduced from John, 2005 [Investigative Ophthalmology and Visual Science, 2005, 46:2650–2661. Copyright 2005, Association for Research in Vision and Ophthalmology].)

Plate 33 Whole-mounted glaucomatous retina showing fanshaped patterns of RGC loss and survival. A, High-resolution survey of a whole-mounted retina from a moderately affected eye stained for axons (green, Smi32) and amacrine cells (red, ChAT) and nuclei counterstained with TOPRO (blue). The axon bundles entering the optic nerve head are markedly reduced and show

sectors of relatively high axon densities alternating with sectors with almost no persisting axons. Scale bar = 500 μm. B–E, High-power views of the boxed areas outlined in A. Scale bar = 100 μm. (See figure 39.3.) (Reproduced from Jacobs et al., 2005 [ Journal of Cell Biology, 2005, 171:313–325. Copyright © 2005, Rockefeller University Press].)

Plate 34 Bax deficiency prevents glaucomatous RGC death but is not required for optic nerve degeneration. RGC layers (A, C, E, and G) and optic nerves (B, D, F, and H) were analyzed in Bax-sufficient and Bax-deficient DBA/2J mice (genotype indi-

cated). Mice were analyzed at preglaucomatous (A–D) and severe glaucomatous (E–H) stages. Bax-deficient DBA/2J mice had severe optic nerve damage but no RGC death. (See figure 39.4.) (Modified from Libby et al., 2005c.)

Plate 35 Radiation treatment prevents glaucomatous optic nerve excavation. A–F, Hematoxylin-eosin-stained sections of untreated and treated DBA/2J mouse eyes (A and B). Optic nerve head (ONH) (A) and retina (B) from nonglaucomatous DBA/2J mice showing large numbers of axons as evidenced by a thick nerve fiber layer (NFL) (arrowheads). ONH (C) and retina (D) of a treated DBA/2J mouse (14 months old) is indistinguishable from nonglaucomatous controls. E and F, In contrast, untreated DBA/2J mice show severe excavation of ONH (*) and no NFL. Cross sections of

the optic nerve from treated (G) and untreated (H) DBA/2J mice stained with PPD, a stain that labels myelin sheath and sick or dying axons. The severe axon loss and scarring in the untreated eye are absent in the treated eye. The vast majority (>96%) of eyes from radiation-treated DBA/2J mice were completely rescued from glaucoma. (See figure 39.5.) (Modified from Anderson et al., 2005. Reproduced from Proceedings of the National Academy of Sciences of the USA, 2005, 102:4566–4571. Copyright © 2005 National Academy of Sciences.)

Plate 36 Mutations in transcription factors and their effect on lens development. A, Histological section through a developing eye of a Pax6 mutant (Pax6Aey11; E17.5) clearly demonstrates the persisting lens stalk (arrow), the connection between the lens and the cornea. B, Histological section of the developing eye of the aphakia

mouse (deletions in the Pitx3 promoter) shows absence of the lens at E18.5; the eyeball is filled with retinal derivatives. C, cornea; R, retina. (See figure 40.1.) (A, From Graw et al., 2005. B, From Semina et al., 2000.)

Plate 37 Mutations in Gja8 and Cryaa. Gross appearance of lenses of the Gja8Aey5 mutant mouse (A) compared with lenses from a CryaaAey7 mutant mouse (B ). The upper row indicates the pheno-

type for the heterozygotes and the lower row that for the homozygous mutants. In both cases, a gene dose effect can be observed. (See figure 40.2.)

Plate 38 Mutations in Cryg. Histological sections of cataractous lenses from two different mutant lines are shown. The mutations have been induced by ENU in the Cryga gene (A) or in the Crygd

gene (B). Inset in the overview marks the magnification, which is given below. The differences in severity are apparent. Bars = 100 μm. (See figure 40.3.) (From Graw et al., 2004.)

Plate 39 Typical histology of EIU and EAU in the mouse. Healthy compared to diseased eye tissue in EIU (A and B) and in EAU (C and D). A, Healthy anterior chamber. Shown is the angle where the iris and ciliary body connect to the sclera. C, cornea; CB, ciliary body; I, iris; S, sclera. B, EIU in a C3H mouse induced by subcutaneous injection of LPS. Note infiltration of inflammatory cells in the angle and around the iris and ciliary processes. Original magnification ×1200. C, Healthy mouse retina.

C, choroid; G, ganglion cell layer; P, photoreceptor cell layer; R, retinal pigment epithelium; S, sclera; V, vitreous. D, EAU in the B10.RIII mouse induced by immunization with IRBP. Note structural disorganization and loss of nuclei in the ganglion and photoreceptor cell layers, retinal folds, subretinal exudate, vasculitis, damage to the retinal pigment epithelium, and choroid inflammation. Original magnification ×1000. (See figure 42.2.) (Photomicrographs courtesy of Dr. Chi-Chao Chan, NEI, NIH.)

Plate 40 Critical checkpoints in EAU pathogenesis. Schematic representation of critical events and checkpoints in the pathogenesis of EAU as revealed by studies in mouse models. (See figure 42.3.)

(This figure was previously published in Caspi, 2006. Copyright does not apply.)

Plate 41 Sections of the central retina from wild-type and knockout mice at P21 after staining with a collagen IV antibody (red), which detects the extracellular matrix of endothelial cells, and diamidinophenylindol/DAPI (blue), which labels cell nuclei. Blood vessels (red) in wild-type mice are present in three layers, indicating completed development of the superficial (ganglion cell layer [GCL]), deep (outer plexiform layer [OPL]), and intermediate (border between the inner plexiform layer [IPL] and inner nuclear

layer [INL]) vessel networks. In contrast, age-matched knockout mice show only enlarged superficial vessels, while the deeper and intermediate networks failed to develop. In addition, the presence of nuclei in the IPL (white arrowheads) may reflect the characteristic disorganization in the GCL. (See figure 43.2.) (Images acquired and provided courtesy of Nikolaus Schäfer, Division of Medical Molecular Genetics, Institute of Medical Genetics, University of Zurich, Switzerland.)

Plate 42 Three-dimensional microscopy of retinal flat mounts stained with anticollagen IV from wild-type and knockout mice at P7. Top panels show an area of approximately 300 × 400 μm from wild-type and knockout mice. Vessels in the knockout are dilated, and the capillary network is less dense than in the wild-type control. Bottom panels (z-axis) show how blood vessels enter the deeper retinal

layers in wild-type mice by angiogenic sprouting. In contrast, this process is abolished in knockout mice, and the vessels do not invade the deeper retinal layers. (See figure 43.3.) (Images acquired using the Zeiss ApoTome technology and provided courtesy of Nikolaus Schäfer, Division of Medical Molecular Genetics, Institute of Medical Genetics, University of Zurich, Switzerland.)

Plate 43 Hematoxylin-eosin-stained sections of whole eyes from wild-type (wt) and norrin knockout (ko) mice at P5, P10, P15, and P21. The hyaloid vessel system (H) in the vitreous body (V) is clearly present in wild-type mice at P5 and P10, and remnants are evident at P15. In knockout mice, the hyaloid vasculature persists through

P21 and beyond, and regression of this vascular network is profoundly delayed. L, lens; O, optic nerve; R, retina. (See figure 43.4.) (Images acquired and provided courtesy of Dr. Ulrich Luhmann, Division of Medical Molecular Genetics, Institute of Medical Genetics, University of Zurich, Switzerland.)

Plate 48 Oxygen is selectively toxic to photoreceptors. A–D, Sections across the retina of C57BL/6 mice exposed to high oxygen levels in inhaled air. Before exposure, dying (red, TUNEL-labeled) cells were rare. Exposure to hyperoxia for 14–35 days (B–D) increased the frequency of dying cells, selectively in the ONL (o). By 35 days, the ONL had thinned and TUNEL+ debris appeared

in the inner nuclear layer (i), probably ingested by Müller cells. The blue dye is a DNA label (bisbenzamide). E and F, When the sheaths of cones were labeled with PNA lectin, the nuclei of some were TUNEL labeled (red), indicating that cones as well as rods were oxygen sensitive. (See figure 46.3.) (From Geller et al., 2006.)

Plate 49 Photoreceptors at the most peripheral margin of the retina are subject to stress from early postnatal life. A–C, The edge of the retina of C57BL/6 mouse retina, with dying cells (bright red, TUNEL labeled) clustering at the edge of P14, P16, and P18. All are in the ONL. D and E, This cluster of dying cells colocalizes with the upregulation of two stress-induced proteins. GFAP is normally expressed (red) only at the inner surface of the retina, by astrocytes (E and G). At the edge, GFAP is upregulated also in Müller cells. FGF-2 is strongly upregulated (green) in photorecep-

tors, in a gradient that is maximal at the end. H, Quantification of the frequency of dying cells in the peripheral-most 100 μm of retina. I, Oxygen influences this distribution of dying cells at the edge of the early postnatal retina. Hypoxia increases photoreceptor death throughout most of the retina; at the edge, however, hyperoxia reduces death, suggesting that the edge-related death is driven by oxygen stress (see the text). Hyperoxia causes a small increase in the frequency of dying cells at the edge of the retina. (See figure 46.4.) (From Mervin and Stone, 2002a, 2002b.)