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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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Blast trauma injures the ocular surface. (A) The majority of mice had calcium deposits in the cornea at baseline. Images showing the most common anterior pathologies detected at three, seven, 14, and 28 days post-blast wave exposure. (B) Corneal edema and hyphema at three days post-blast wave exposure. (C) Corneal edema and neovascularization at seven days post-blast wave exposure. (D) A corneal growth with neovascularization and hyphema at 14 days post-blast wave exposure. (E) Corneal scarring and neovascularization at 28 days post-blast wave exposure. Arrows indicate pathologies.
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Fig1: Blast trauma injures the ocular surface. (A) The majority of mice had calcium deposits in the cornea at baseline. Images showing the most common anterior pathologies detected at three, seven, 14, and 28 days post-blast wave exposure. (B) Corneal edema and hyphema at three days post-blast wave exposure. (C) Corneal edema and neovascularization at seven days post-blast wave exposure. (D) A corneal growth with neovascularization and hyphema at 14 days post-blast wave exposure. (E) Corneal scarring and neovascularization at 28 days post-blast wave exposure. Arrows indicate pathologies.

Mentions: Blast wave exposure caused numerous anterior injuries that, in some cases, varied depending on time after the blast (Tables 2, 3, and 4). This is in contrast to the lack of anterior pathologies in the majority of C57Bl/6 mice after eye blast [8,9]. In both cases, no eye drops or ointments were provided in order to detect all pathologies caused by an eye-directed blast to the naïve eye. Representative images of these pathologies after exposure to a 26 psi blast wave are shown in Figure 1. The eyes appeared normal immediately after the blast wave, but at three days significant pathologies were present including CE, hyphema, cataracts, and a few cases of CNV. The incidence of CE after a 23, 26, or 30 psi blast wave remained high up to 28 days; 100%, 86%, and 60%, respectively. The incidence of hyphema in all blast groups peaked at three days after blast wave exposure and was completely absent at 28 days post-blast wave exposure. The percentage of eyes with hyphema at three days was 8%, 26%, and 25% after a 23, 26, and 30 psi blast wave, respectively. In contrast, the number of eyes with CNV increased over time post-blast wave exposure. At three days post-blast wave exposure 31%, 17%, and 0% of 23, 26, and 30 psi eyes, respectively, exhibited signs of CNV. At 28 days 80%, 29%, and 45% of 23, 26, and 30 psi eyes, respectively, had CNV. Exposure to a 26 psi blast wave induced the most reproducible and clinically relevant damage profile. Therefore, this pressure level was used for the remaining experiments.Table 2


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

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

Blast trauma injures the ocular surface. (A) The majority of mice had calcium deposits in the cornea at baseline. Images showing the most common anterior pathologies detected at three, seven, 14, and 28 days post-blast wave exposure. (B) Corneal edema and hyphema at three days post-blast wave exposure. (C) Corneal edema and neovascularization at seven days post-blast wave exposure. (D) A corneal growth with neovascularization and hyphema at 14 days post-blast wave exposure. (E) Corneal scarring and neovascularization at 28 days post-blast wave exposure. Arrows indicate pathologies.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Blast trauma injures the ocular surface. (A) The majority of mice had calcium deposits in the cornea at baseline. Images showing the most common anterior pathologies detected at three, seven, 14, and 28 days post-blast wave exposure. (B) Corneal edema and hyphema at three days post-blast wave exposure. (C) Corneal edema and neovascularization at seven days post-blast wave exposure. (D) A corneal growth with neovascularization and hyphema at 14 days post-blast wave exposure. (E) Corneal scarring and neovascularization at 28 days post-blast wave exposure. Arrows indicate pathologies.
Mentions: Blast wave exposure caused numerous anterior injuries that, in some cases, varied depending on time after the blast (Tables 2, 3, and 4). This is in contrast to the lack of anterior pathologies in the majority of C57Bl/6 mice after eye blast [8,9]. In both cases, no eye drops or ointments were provided in order to detect all pathologies caused by an eye-directed blast to the naïve eye. Representative images of these pathologies after exposure to a 26 psi blast wave are shown in Figure 1. The eyes appeared normal immediately after the blast wave, but at three days significant pathologies were present including CE, hyphema, cataracts, and a few cases of CNV. The incidence of CE after a 23, 26, or 30 psi blast wave remained high up to 28 days; 100%, 86%, and 60%, respectively. The incidence of hyphema in all blast groups peaked at three days after blast wave exposure and was completely absent at 28 days post-blast wave exposure. The percentage of eyes with hyphema at three days was 8%, 26%, and 25% after a 23, 26, and 30 psi blast wave, respectively. In contrast, the number of eyes with CNV increased over time post-blast wave exposure. At three days post-blast wave exposure 31%, 17%, and 0% of 23, 26, and 30 psi eyes, respectively, exhibited signs of CNV. At 28 days 80%, 29%, and 45% of 23, 26, and 30 psi eyes, respectively, had CNV. Exposure to a 26 psi blast wave induced the most reproducible and clinically relevant damage profile. Therefore, this pressure level was used for the remaining experiments.Table 2

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