automated-compression-testing-of-the-ocular-lens

Automated Compression Testing of the Ocular Lens

The biomechanical properties of the ocular lens are essential to its function as a variable power optical element. These properties change dramatically ...

The Ohio State University

Many disease pathologies, particularly in the eye, are induced by oxidative stress. In particular, injury to the optic nerve (ON), or optic neuropathy, is one of the most common causes of vision loss. Traumatic optic neuropathy (TON) occurs when the ON is damaged following blunt or penetrating trauma to either the head or eye. Currently, there is no effective treatment for TON, only management options, namely the systematic delivery of corticosteroids and surgical decompression of the optic nerve. Unfortunately, neither option alleviates the generation of reactive oxygen species (ROS) which are responsible for downstream damage to the ON. Additionally, the systemic delivery of corticosteroids can cause fatal off-target effects in cases with brain involvement. In this study, we developed a tunable injectable hydrogel delivery system for local methylene blue (MB) delivery using an internal method of crosslinking. MB was chosen due to its ROS scavenging ability and neuroprotective properties. Our MB-loaded polymeric scaffold demonstrated prolonged release of MB as well as in situ gel formation. Additionally, following rheological characterization, these alginate hydrogels demonstrated minimal cytotoxicity to human retinal pigment epithelial cells in vitro and exhibited injection feasibility through small-gauge needles. Our chosen MB concentrations displayed a high degree of ROS scavenging following release from the alginate hydrogels, suggesting this approach may be successful in reducing ROS levels following ON injury, or could be applied to other ocular injuries.

Tunable alginate hydrogels as injectable drug delivery vehicles for optic neuropathy.

 Presbyopia-the progressive loss of near focus with age-is primarily a result of changes in lens biomechanics. In particular, the shape of the ocular lens in the absence of zonular tension changes significantly throughout adulthood. Contributors to this change in shape are changes in lens biomechanical properties, continuous volumetric growth lens, and possibly remodeling of the lens capsule. Knowledge in this area is growing rapidly, so the purpose of this mini-review was to summarize and synthesize these gains. We review the recent literature in this field. The mechanisms governing age-related changes in biomechanical properties remains unknown. We have recently shown that lens growth may be driven by zonular tension. The same mechanobiological mechanism driving lens growth may also lead to remodeling of the capsule, though this remains to be demonstrated. This mini-review focuses on identifying mechanisms which cause these age-related changes, suggesting future work which may elucidate these mechanisms, and briefly discusses ongoing efforts to develop a non-surgical approach for therapeutic management of presbyopia. We also propose a simple model linking lens growth and biomechanical properties.

A Review of Lens Biomechanical Contributions to Presbyopia.

The etiology of age-related cortical cataracts is not well understood but is speculated to be related to alterations in cell adhesion and/or the changing mechanical stresses occurring in the lens with time. The role of cell adhesion in maintaining lens transparency with age is difficult to assess because of the developmental and physiological roles that well-characterized adhesion proteins have in the lens. This report demonstrates that Arvcf, a member of the p120-catenin subfamily of catenins that bind to the juxtamembrane domain of cadherins, is an essential fiber cell protein that preserves lens transparency with age in mice. No major developmental defects are observed in the absence of , however, cortical cataracts emerge in all animals examined older than 6-months of age. While opacities are not obvious in young animals, histological anomalies are observed in lenses at 4-weeks that include fiber cell separations, regions of hexagonal lattice disorganization, and absence of immunolabeled membranes. Compression analysis of whole lenses also revealed that Arvcf is required for their normal biomechanical properties. Immunofluorescent labeling of control and Arvcf-deficient lens fiber cells revealed a reduction in membrane localization of N-cadherin, β-catenin, and αN-catenin. Furthermore, super-resolution imaging demonstrated that the reduction in protein membrane localization is correlated with smaller cadherin nanoclusters. Additional characterization of lens fiber cell morphology with electron microscopy and high resolution fluorescent imaging also showed that the cellular protrusions of fiber cells are abnormally elongated with a reduction and disorganization of cadherin complex protein localization. Together, these data demonstrate that Arvcf is required to maintain transparency with age by mediating the stability of the N-cadherin protein complex in adherens junctions.

Arvcf Dependent Adherens Junction Stability is Required to Prevent Age-Related Cortical Cataracts.

The brain and the retina share many physiological similarities, which allows the retina to serve as a model of CNS disease and disorder. In instances of trauma, the eye can even indicate damage to the brain  abnormalities observed such as irregularities in pupillary reflexes in suspected traumatic brain injury (TBI) patients. Elevation of reactive oxygen species (ROS) has been observed in neurodegenerative disorders and in both traumatic optic neuropathy (TON) and in TBI. In a healthy system, ROS play a pivotal role in cellular communication, but in neurodegenerative diseases and post-trauma instances, ROS elevation can exacerbate neurodegeneration in both the brain and the retina. Increased ROS can overwhelm the inherent antioxidant systems which are regulated  mitochondrial processes. The overabundance of ROS can lead to protein, DNA, and other forms of cellular damage which ultimately result in apoptosis. Even though elevated ROS have been observed to be a major cause in the neurodegeneration observed after TON and TBI, many antioxidants therapeutic strategies fail. In order to understand why these therapeutic approaches fail further research into the direct injury cascades must be conducted. Additional therapeutic approaches such as therapeutics capable of anti-inflammatory properties and suppression of other neurodegenerative processes may be needed for the treatment of TON, TBI, and neurodegenerative diseases.

Oxidative stress in the brain and retina after traumatic injury.

The ocular lens is the primary organ within the eye responsible for accommodation. During accommodation, the lens is subject to biomechanical forces. We previously demonstrated that stretching the porcine lens can increase lens epithelial cell proliferation. Although murine lenses are commonly employed in lens research, murine lens stretching has remained unexplored. Murine lens stretching thus represents a novel source of potential discovery in lens research. In the present study, we describe a method for stretching the murine lens by compressing the murine globe embedded in a hydrogel. We hypothesized that, as the eye is compressed along the optic axis, the lens would stretch through zonular tension due to the equatorial region of the eye bulging outward. Our results showed that this led to a compression-dependent increase in murine lens epithelial cell proliferation, suggesting that compression of the embedded murine globe is a viable technique for studying the mechanobiology of the lens epithelium.

Article	Year
Tunable alginate hydrogels as injectable drug delivery vehicles for optic neuropathy. Journal of biomedical materials research. Part A\| PubMed ID: 35607724	2022
A Review of Lens Biomechanical Contributions to Presbyopia. Current eye research\| PubMed ID: 35713207	2023
Arvcf Dependent Adherens Junction Stability is Required to Prevent Age-Related Cortical Cataracts. Frontiers in cell and developmental biology\| PubMed ID: 35874813	2022
Oxidative stress in the brain and retina after traumatic injury. Frontiers in neuroscience\| PubMed ID: 36816125	2023
A method for generating zonular tension in the murine eye by embedding and compressing the globe in a hydrogel. Experimental eye research\| PubMed ID: 38311284	2024

Wade Rich

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