Immunopathology of terminal complement activation and complement C5 blockade creating a pro-survival and organ-protective phenotype in trauma.

Background And Purpose: Traumatic haemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of a TCA inhibitor (nomacopan) on organ damage and survival in vivo.

Evaluation of the potential eye hazard at visible wavelengths of the supercontinuum generated by an ultrafast NIR laser in water.

Lasers with ultrashort pulse durations have become ubiquitous in various applications, including ocular surgery. Therefore, we need to consider the role of nonlinear optical effects, such as supercontinuum generation during propagation within the ocular media, when evaluating their potential hazard. We used a NIR femtosecond laser to generate a supercontinuum within an artificial eye.

Development and Characterization of a Benchtop Corneal Puncture Injury Model.

During recent military operations, eye-related injuries have risen in frequency due to increased use of explosive weaponry which often result in corneal puncture injuries. These have one of the poorest visual outcomes for wounded soldiers, often resulting in blindness due to the large variations in injury shape, size, and severity. As a result, improved therapeutics are needed which can stabilize the injury site and promote wound healing.

Altered expression of aquaporin 1 and aquaporin 5 in the cornea after primary blast exposure.

Purpose: Our study aimed to determine whether the altered expression of biomarkers linked to corneal injuries, such as the edema-regulating proteins aquaporin-1 and aquaporin-5 (AQP1 and AQP5), occurred following primary blast exposure.

Methods: Adult male Dutch Belted rabbits were anesthetized and exposed to blast waves with peak overpressures of 142.5-164.

Blast Exposure Induces Ocular Functional Changes with Increasing Blast Over-pressures in a Rat Model.

: Blast-related brain and ocular injuries can lead to acute and chronic visual dysfunction. The chronic visual consequences of blast exposure and its progression remain unclear. The goal of this study is to analyze ocular functional response to four levels of blast exposure and identify a threshold of blast exposure leading to acute and chronic visual dysfunction.

Early Complement and Fibrinolytic Activation in a Rat Model of Blast-Induced Multi-Organ Damage.

Objective: Blast injury is associated with multi-organ failure (MOF), causing significant morbidity and mortality in trauma patients. However, the pathogenesis of blast-induced MOF still remains obscure. In this study, we evaluate the pathophysiological changes related to blast-induced MOF in a clinically relevant rat model of blast injury.

Repeat low-level blast exposure increases transient receptor potential vanilloid 1 (TRPV1) and endothelin-1 (ET-1) expression in the trigeminal ganglion.

Blast-associated sensory and cognitive trauma sustained by military service members is an area of extensively studied research. Recent studies in our laboratory have revealed that low-level blast exposure increased expression of transient receptor potential vanilloid 1 (TRPV1) and endothelin-1 (ET-1), proteins well characterized for their role in mediating pain transmission, in the cornea. Determining the functional consequences of these alterations in protein expression is critical to understanding blast-related sensory trauma.

Simulations of Porcine Eye Exposure to Primary Blast Insult.

Purpose: A computational model of the porcine eye was developed to simulate primary blast exposure. This model facilitates understanding of blast-induced injury mechanisms.

Methods: A computational model of the porcine eye was used to simulate the effects of primary blast loading for comparison with experimental findings from shock tube experiments.

Laser-induced retinal damage threshold for repetitive-pulse exposure to 100-μs pulses.

The laser-induced retinal injury thresholds for repetitive-pulse exposures to 100-μs-duration pulses at a wavelength of 532 nm have been determined for exposures of up to 1000 pulses in an in vivo model. The ED50 was measured for pulse repetition frequencies of 50 and 1000 Hz. Exposures to collimated beams producing a minimal retinal beam spot and to divergent beams producing a 100-μm-diameter retinal beam spot were considered.

Damage threshold from large retinal spot size repetitive-pulse laser exposures.

The retinal damage thresholds for large spot size, multiple-pulse exposures to a Q-switched, frequency doubled Nd:YAG laser (532 nm wavelength, 7 ns pulses) have been measured for 100 μm and 500 μm retinal irradiance diameters. The ED50, expressed as energy per pulse, varies only weakly with the number of pulses, n, for these extended spot sizes. The previously reported threshold for a multiple-pulse exposure for a 900 μm retinal spot size also shows the same weak dependence on the number of pulses.

Anatomical manifestations of primary blast ocular trauma observed in a postmortem porcine model.

Purpose: We qualitatively describe the anatomic features of primary blast ocular injury observed using a postmortem porcine eye model. Porcine eyes were exposed to various levels of blast energy to determine the optimal conditions for future testing.

Methods: We studied 53 enucleated porcine eyes: 13 controls and 40 exposed to a range of primary blast energy levels.

Laser-induced retinal damage threshold measurements with wavefront correction.

An adaptive optics (AO) system was incorporated into a laser retinal exposure setup in order to correct for refractive error and higher-order aberrations of the nonhuman primate (NHP) eye during an in vivo retinal ED(50) measurement. Using this system, the ED(50) for a 100-ms, 532-nm small spot size exposure was measured to be 1.05 mJ total intraocular energy (TIE), a reduction of 22% from the value measured without aberration correction.

Laser retinal thermal damage threshold: impact of small-scale ocular motion.

The impact of the small-scale ocular motion that occurs during steady gaze on the retinal thermal damage threshold for long-duration laser exposures is investigated. Exposure durations from 100 msec to 50 sec are considered. Experimentally recorded eye movement data are input into a numerical simulation to calculate the increase in temperature experienced by the retina during an exposure to a continuous wave laser.

Computer model to investigate the effect of eye movements on retinal heating during long-duration fixation on a laser source.

A computer simulation called RHME (Retinal Heating in Moving Eye) is developed to simulate the heating pattern that occurs in the retina during a long-duration exposure to a continuous wave laser beam. The simulation takes into account eye movements that occur during a deliberate fixation. Due to the rapid (millisecond) thermal time scale for heating and cooling, only the area of the retina directly exposed to the laser sustains an increased temperature.

Effect of source intensity on ability to fixate: implications for laser safety.

During long-term viewing of a continuous light source, head and eye movements affect the distribution of energy deposited in the retina. Previous studies of eye movements during a fixation task provided data used for revising the safety limits for long-term viewing of such sources. These studies have been continued to determine the effect of source brightness on the nature of fixational eye movements.

Retinal image motion during deliberate fixation: implications to laser safety for long duration viewing.

With the easy attainability of hand-held laser devices and the burgeoning light emitting diode (LED) technology, safety standards for long-term viewing of continuous light sources are being scrutinized. One concern is with quantifying the effect of head and eye movements on the distribution of energy over the retina. This experiment describes target motion over the retina as a result of head and eye movements during a deliberate fixation task.