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Exacerbation of blast-induced ocular trauma by an immune response.

Bricker-Anthony C, Hines-Beard J, D'Surney L, Rex TS - J Neuroinflammation (2014)

Bottom Line: The electroretinogram (ERG) showed an early deficit in the a wave that recovered over time.Both visual acuity and the ERG b wave showed an early decrease, then a transient improvement that was followed by further decline at 28 days post-blast wave exposure.In contrast, inner retinal dysfunction seems to drive later vision loss.

View Article: PubMed Central - PubMed

Affiliation: Vanderbilt Eye Institute, Vanderbilt University, 11425 MRB IV, 2213 Garland Ave., Nashville, TN, 37232, USA. courtney.m.bricker@Vanderbilt.Edu.

ABSTRACT

Background: Visual prognosis after an open globe injury is typically worse than after a closed globe injury due, in part, to the immune response that ensues following open globe trauma. There is a need for an animal model of open globe injury in order to investigate mechanisms of vision loss and test potential therapeutics.

Methods: The left eyes of DBA/2 J mice were exposed to an overpressure airwave blast. This strain lacks a fully functional ocular immune privilege, so even though the blast wave does not rupture the globe, immune infiltrate and neuroinflammation occurs as it would in an open globe injury. For the first month after blast wave exposure, the gross pathology, intraocular pressure, visual function, and retinal integrity of the blast-exposed eyes were monitored. Eyes were collected at three, seven, and 28 days to study the histology of the cornea, retina, and optic nerve, and perform immunohistochemical labeling with markers of cell death, oxidative stress, and inflammation.

Results: The overpressure airwave caused anterior injuries including corneal edema, neovascularization, and hyphema. Immune infiltrate was detected throughout the eyes after blast wave exposure. Posterior injuries included occasional retinal detachments and epiretinal membranes, large retinal pigment epithelium vacuoles, regional photoreceptor cell death, and glial reactivity. Optic nerve degeneration was evident at 28 days post-blast wave exposure. The electroretinogram (ERG) showed an early deficit in the a wave that recovered over time. Both visual acuity and the ERG b wave showed an early decrease, then a transient improvement that was followed by further decline at 28 days post-blast wave exposure.

Conclusions: Ocular blast injury in the DBA/2 J mouse recapitulates damage that is characteristic of open globe injuries with the advantage of a physically intact globe that prevents complications from infection. The injury was more severe in DBA/2 J mice than in C57Bl/6 J mice, which have an intact ocular immune privilege. Early injury to the outer retina mostly recovers over time. In contrast, inner retinal dysfunction seems to drive later vision loss.

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Cell death occurs in small, focal areas after blast wave exposure. (A) A schematic representing an enface view of the retina showing the average number and distribution of affected (TUNEL-positive) areas (red bars) detected in retinal cross-sections collected in serial through the eye three days post-blast wave exposure. (B) Montage of low magnification epifluorescence micrographs of a retina three days post-blast wave exposure. White boxes indicate affected areas (scale bar is 250 μm). (C-E) Higher magnification epifluorescence micrographs of TUNEL (red) and DAPI (blue) in a control retina (C), and affected (D) and unaffected (E) regions of the retina shown in (B). The scale bar in (C) represents 50 μm and also applies to (D) and (E). ON = optic nerve head; GCL = ganglion cell layer; INL = inner nuclear layer; ONL = outer nuclear layer.
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Fig7: Cell death occurs in small, focal areas after blast wave exposure. (A) A schematic representing an enface view of the retina showing the average number and distribution of affected (TUNEL-positive) areas (red bars) detected in retinal cross-sections collected in serial through the eye three days post-blast wave exposure. (B) Montage of low magnification epifluorescence micrographs of a retina three days post-blast wave exposure. White boxes indicate affected areas (scale bar is 250 μm). (C-E) Higher magnification epifluorescence micrographs of TUNEL (red) and DAPI (blue) in a control retina (C), and affected (D) and unaffected (E) regions of the retina shown in (B). The scale bar in (C) represents 50 μm and also applies to (D) and (E). ON = optic nerve head; GCL = ganglion cell layer; INL = inner nuclear layer; ONL = outer nuclear layer.

Mentions: After blast wave exposure, all retinas had areas with TUNEL-positive cells (affected areas) at three (n = 5) and seven days post-injury (n = 9), while 82% of retinas were TUNEL-positive at 28 days post-injury (n = 11). Cell death was typically present in patches and not evenly distributed across the retina (Figure 7). These affected areas were primarily in the mid-peripheral retina, but occasionally were also detected in central retina (Figure 7A). Representative images of TUNEL in affected and unaffected areas of retina three days after blast wave exposure are shown in Figure 7D, E. Areas with retinal folds had the highest density of TUNEL-positive cells.Figure 7


Exacerbation of blast-induced ocular trauma by an immune response.

Bricker-Anthony C, Hines-Beard J, D'Surney L, Rex TS - J Neuroinflammation (2014)

Cell death occurs in small, focal areas after blast wave exposure. (A) A schematic representing an enface view of the retina showing the average number and distribution of affected (TUNEL-positive) areas (red bars) detected in retinal cross-sections collected in serial through the eye three days post-blast wave exposure. (B) Montage of low magnification epifluorescence micrographs of a retina three days post-blast wave exposure. White boxes indicate affected areas (scale bar is 250 μm). (C-E) Higher magnification epifluorescence micrographs of TUNEL (red) and DAPI (blue) in a control retina (C), and affected (D) and unaffected (E) regions of the retina shown in (B). The scale bar in (C) represents 50 μm and also applies to (D) and (E). ON = optic nerve head; GCL = ganglion cell layer; INL = inner nuclear layer; ONL = outer nuclear layer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4264554&req=5

Fig7: Cell death occurs in small, focal areas after blast wave exposure. (A) A schematic representing an enface view of the retina showing the average number and distribution of affected (TUNEL-positive) areas (red bars) detected in retinal cross-sections collected in serial through the eye three days post-blast wave exposure. (B) Montage of low magnification epifluorescence micrographs of a retina three days post-blast wave exposure. White boxes indicate affected areas (scale bar is 250 μm). (C-E) Higher magnification epifluorescence micrographs of TUNEL (red) and DAPI (blue) in a control retina (C), and affected (D) and unaffected (E) regions of the retina shown in (B). The scale bar in (C) represents 50 μm and also applies to (D) and (E). ON = optic nerve head; GCL = ganglion cell layer; INL = inner nuclear layer; ONL = outer nuclear layer.
Mentions: After blast wave exposure, all retinas had areas with TUNEL-positive cells (affected areas) at three (n = 5) and seven days post-injury (n = 9), while 82% of retinas were TUNEL-positive at 28 days post-injury (n = 11). Cell death was typically present in patches and not evenly distributed across the retina (Figure 7). These affected areas were primarily in the mid-peripheral retina, but occasionally were also detected in central retina (Figure 7A). Representative images of TUNEL in affected and unaffected areas of retina three days after blast wave exposure are shown in Figure 7D, E. Areas with retinal folds had the highest density of TUNEL-positive cells.Figure 7

Bottom Line: The electroretinogram (ERG) showed an early deficit in the a wave that recovered over time.Both visual acuity and the ERG b wave showed an early decrease, then a transient improvement that was followed by further decline at 28 days post-blast wave exposure.In contrast, inner retinal dysfunction seems to drive later vision loss.

View Article: PubMed Central - PubMed

Affiliation: Vanderbilt Eye Institute, Vanderbilt University, 11425 MRB IV, 2213 Garland Ave., Nashville, TN, 37232, USA. courtney.m.bricker@Vanderbilt.Edu.

ABSTRACT

Background: Visual prognosis after an open globe injury is typically worse than after a closed globe injury due, in part, to the immune response that ensues following open globe trauma. There is a need for an animal model of open globe injury in order to investigate mechanisms of vision loss and test potential therapeutics.

Methods: The left eyes of DBA/2 J mice were exposed to an overpressure airwave blast. This strain lacks a fully functional ocular immune privilege, so even though the blast wave does not rupture the globe, immune infiltrate and neuroinflammation occurs as it would in an open globe injury. For the first month after blast wave exposure, the gross pathology, intraocular pressure, visual function, and retinal integrity of the blast-exposed eyes were monitored. Eyes were collected at three, seven, and 28 days to study the histology of the cornea, retina, and optic nerve, and perform immunohistochemical labeling with markers of cell death, oxidative stress, and inflammation.

Results: The overpressure airwave caused anterior injuries including corneal edema, neovascularization, and hyphema. Immune infiltrate was detected throughout the eyes after blast wave exposure. Posterior injuries included occasional retinal detachments and epiretinal membranes, large retinal pigment epithelium vacuoles, regional photoreceptor cell death, and glial reactivity. Optic nerve degeneration was evident at 28 days post-blast wave exposure. The electroretinogram (ERG) showed an early deficit in the a wave that recovered over time. Both visual acuity and the ERG b wave showed an early decrease, then a transient improvement that was followed by further decline at 28 days post-blast wave exposure.

Conclusions: Ocular blast injury in the DBA/2 J mouse recapitulates damage that is characteristic of open globe injuries with the advantage of a physically intact globe that prevents complications from infection. The injury was more severe in DBA/2 J mice than in C57Bl/6 J mice, which have an intact ocular immune privilege. Early injury to the outer retina mostly recovers over time. In contrast, inner retinal dysfunction seems to drive later vision loss.

Show MeSH
Related in: MedlinePlus