anterior-segment-organ-culture-platform-for-tracking-open-globe

Anterior Segment Organ Culture Platform for Tracking Open Globe Injuries and Therapeutic Performance

Open globe injuries have poor visual outcomes, often resulting in permanent loss of vision. This is partly due to an extended delay between injury and ...

Fort Sam Houston

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. Unfortunately, current corneal puncture injury models are not capable of producing irregularly shaped, large, high-speed injuries as seen on the battlefield, making relevant therapeutic development challenging. Here, we present a benchtop corneal puncture injury model for use with enucleated eyes that utilizes a high-speed solenoid device suitable for creating military-relevant injuries. We first established system baselines and ocular performance metrics, standardizing the different aspects of the benchtop model to ensure consistent results and properly account for tissue variability. The benchtop model was evaluated with corneal puncture injury objects up to 4.2 mm in diameter which generated intraocular pressure levels exceeding 1500 mmHg. Overall, the created benchtop model provides an initial platform for better characterizing corneal puncture injuries as seen in a military relevant clinical setting and a realistic approach for assessing potential therapeutics.

Development and Characterization of a Benchtop Corneal Puncture Injury Model.

Open-globe injuries can result in permanent vision loss, partly due to extended delays between injury and medical intervention. Even with early intervention, the management of open-globe injuries remains a challenge for ophthalmologists, mostly due to inadequate or suboptimal current therapies. To aid in the development of novel therapeutics and track toxicological and pathophysiological changes, this article details an open-globe injury platform capable of inducing injuries in enucleated porcine eyes. The injury platform relies on a high-speed solenoid device to mimic explosive injury scenarios, allowing for large, complex injury shapes and sizes that are often observed in casualties and are more difficult to treat. The system can be implemented with precise computer control of the injury mechanism to allow for more complex setups. Also, the system can make use of real-time intraocular pressure measurement to track changes during injury induction and to assess therapeutic efficacy for restoring intraocular pressure and the integrity of the eye. These protocols will assist with implementation of the injury model in prospective laboratories seeking to develop therapeutics or studying biological changes that occur from this type of traumatic injury. Published 2020. U.S. Government. Basic Protocol 1: Preparing gelatin molds and porcine eye tissue Basic Protocol 2: Creating an open-globe injury using a solenoid device Alternate Protocol 1: Constructing a computer-controlled system for open-globe injury Alternate Protocol 2: Constructing a pressure measurement system for tracking intraocular pressure Support Protocol 1: Assessing ocular compliance in porcine eyes Support Protocol 2: Assessing outflow rate from the anterior chamber Support Protocol 3: Assessing burst pressure in porcine eyes.

An Open-Globe Porcine Injury Platform for Assessing Therapeutics and Characterizing Biological Effects.

Open-globe injuries have poor visual outcomes and have increased in frequency. The current standard of care is inadequate, and a therapeutic is needed to stabilize the injury until an ophthalmic specialist is reached. Unfortunately, current models or test platforms for open-globe injuries are insufficient. Here, we develop and characterize an open-globe injury model using an anterior segment organ-culture platform that allows therapeutic assessment for up to 72 h post-injury. Anterior segments maintained in organ culture were kept at physiological intraocular pressure throughout, and puncture injuries were created using a novel pneumatic-powered system. This system can create high-speed, military-relevant injuries up to 4.5 mm in diameter through the cornea. From intraocular pressure readings, we confirmed a loss of pressure across the 72 h after open-globe injury. Proof-of-concept studies with a Dermabond tissue adhesive were performed to show how this model system could track therapeutic performance for 72 h. Overall, the organ-culture platform was found to be a suitable next step towards modeling open-globe injuries and assessing wound closure over the critical 72 h post-injury. With improved models such as this, novel biomaterial therapeutics development can be accelerated, improving care, and, thus, improving the prognosis for the patients.

Characterization of an anterior segment organ culture model for open globe injuries.

Open-globe ocular injuries have increased in frequency in recent combat operations due to increased use of explosive weaponry. Unfortunately, open-globe injuries have one of the worst visual outcomes for the injured warfighter, often resulting in permanent loss of vision. To improve visual recovery, injuries need to be stabilized quickly following trauma, in order to restore intraocular pressure and create a watertight seal. Here, we assess four off-the-shelf (OTS), commercially available tissue adhesives for their ability to seal military-relevant corneal perforation injuries (CPIs).

Article	Year
Development and Characterization of a Benchtop Corneal Puncture Injury Model. Scientific reports\| PubMed ID: 32144320	2020
An Open-Globe Porcine Injury Platform for Assessing Therapeutics and Characterizing Biological Effects. Current protocols in toxicology\| PubMed ID: 33107694	2020
Characterization of an anterior segment organ culture model for open globe injuries. Scientific reports\| PubMed ID: 33879808	2021
Assessment of Commercial Off-the-Shelf Tissue Adhesives for Sealing Military-Relevant Corneal Perforation Injuries. Military medicine\| PubMed ID: 33959769	2021

Eric J. Snider

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