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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 two waves after blast wave exposure. (A) Pie chart showing the distribution of TUNEL-positive cells through the retinal layers after blast wave exposure. (B) The percentage of total retina containing TUNEL-positive cells at each time point. (C) The average number of TUNEL-positive cells per mm total retina after blast wave exposure. (D) The average number of TUNEL-positive cells per mm within the affected areas after blast wave exposure. Error bars represent SEM for each time point. GCL = ganglion cell layer; INL = inner nuclear layer; ONL = outer nuclear layer.
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Fig8: Cell death occurs in two waves after blast wave exposure. (A) Pie chart showing the distribution of TUNEL-positive cells through the retinal layers after blast wave exposure. (B) The percentage of total retina containing TUNEL-positive cells at each time point. (C) The average number of TUNEL-positive cells per mm total retina after blast wave exposure. (D) The average number of TUNEL-positive cells per mm within the affected areas after blast wave exposure. Error bars represent SEM for each time point. GCL = ganglion cell layer; INL = inner nuclear layer; ONL = outer nuclear layer.

Mentions: The percentage of total retina containing TUNEL-positive cells, density of TUNEL-positive cells, and retinal layer affected were quantified (Figure 8). The majority of TUNEL-positive nuclei, 82%, were located in the ONL at three days after injury (Figure 8A). A smaller percentage of TUNEL-positive cells were detected in the INL and GCL, 12% and 6%, respectively, at three days post-blast wave exposure (Figure 8A). This ratio was similar at seven and 28 days post-blast wave exposure: 70% and 83%, respectively, located in the ONL; 27% and 16%, respectively, detected in the INL; and 3% and 1%, respectively, located in the GCL. TUNEL-positive nuclei were present in 13 ± 8% of the retina at three days post-injury, 2 ± 0.2% at seven days post-blast wave exposure, and 5 ± 1% of the retina at 28 days post-blast wave exposure (Figure 8B). When calculated in terms of total retina length, the density of TUNEL was very low, but retained the same trend of higher levels at three days as compared to 28 days. The number of TUNEL-positive nuclei per mm total retina was 15 ± 9, 0.1 ± 0.1, and 11 ± 4 at three, seven, and 28 days post-blast wave exposure (Figure 8C). Within the affected regions, the density of TUNEL-positive cells was 87 ± 44, 10 ± 3, and 215 ± 57 nuclei per mm retina at three, seven, and 28 days after blast wave exposure, respectively (Figure 8D). These results demonstrate that the area occupied by TUNEL-positive cells decreases over time, but the density of TUNEL-positive cells within affected areas increases.Figure 8


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 two waves after blast wave exposure. (A) Pie chart showing the distribution of TUNEL-positive cells through the retinal layers after blast wave exposure. (B) The percentage of total retina containing TUNEL-positive cells at each time point. (C) The average number of TUNEL-positive cells per mm total retina after blast wave exposure. (D) The average number of TUNEL-positive cells per mm within the affected areas after blast wave exposure. Error bars represent SEM for each time point. 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

Fig8: Cell death occurs in two waves after blast wave exposure. (A) Pie chart showing the distribution of TUNEL-positive cells through the retinal layers after blast wave exposure. (B) The percentage of total retina containing TUNEL-positive cells at each time point. (C) The average number of TUNEL-positive cells per mm total retina after blast wave exposure. (D) The average number of TUNEL-positive cells per mm within the affected areas after blast wave exposure. Error bars represent SEM for each time point. GCL = ganglion cell layer; INL = inner nuclear layer; ONL = outer nuclear layer.
Mentions: The percentage of total retina containing TUNEL-positive cells, density of TUNEL-positive cells, and retinal layer affected were quantified (Figure 8). The majority of TUNEL-positive nuclei, 82%, were located in the ONL at three days after injury (Figure 8A). A smaller percentage of TUNEL-positive cells were detected in the INL and GCL, 12% and 6%, respectively, at three days post-blast wave exposure (Figure 8A). This ratio was similar at seven and 28 days post-blast wave exposure: 70% and 83%, respectively, located in the ONL; 27% and 16%, respectively, detected in the INL; and 3% and 1%, respectively, located in the GCL. TUNEL-positive nuclei were present in 13 ± 8% of the retina at three days post-injury, 2 ± 0.2% at seven days post-blast wave exposure, and 5 ± 1% of the retina at 28 days post-blast wave exposure (Figure 8B). When calculated in terms of total retina length, the density of TUNEL was very low, but retained the same trend of higher levels at three days as compared to 28 days. The number of TUNEL-positive nuclei per mm total retina was 15 ± 9, 0.1 ± 0.1, and 11 ± 4 at three, seven, and 28 days post-blast wave exposure (Figure 8C). Within the affected regions, the density of TUNEL-positive cells was 87 ± 44, 10 ± 3, and 215 ± 57 nuclei per mm retina at three, seven, and 28 days after blast wave exposure, respectively (Figure 8D). These results demonstrate that the area occupied by TUNEL-positive cells decreases over time, but the density of TUNEL-positive cells within affected areas increases.Figure 8

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