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Biomedical subjects

Rejean Munger

Publications and source records attributed to Rejean Munger.

7 recordsLinked to original sources

A simple, cross-linked collagen tissue substitute for corneal implantation.

PURPOSE: To develop a simple corneal substitute from cross-linked collagen. METHODS: Porcine type I collagen (10%; pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS: Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host-graft integration. CONCLUSIONS: Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations.

Animals↗

Wavefront-guided correction of ocular aberrations: are phase plate and refractive surgery solutions equal?

Wavefront-guided laser eye surgery has been recently introduced and holds the promise of correcting not only defocus and astigmatism in patients but also higher-order aberrations. Research is just beginning on the implementation of wavefront-guided methods in optical solutions, such as phase-plate-based spectacles, as alternatives to surgery. We investigate the theoretical differences between the implementation of wavefront-guided surgical and phase plate corrections. The residual aberrations of 43 model eyes are calculated after simulated refractive surgery and also after a phase plate is placed in front of the untreated eye. In each case, the current wavefront-guided paradigm that applies a direct map of the ocular aberrations to the correction zone is used. The simulation results demonstrate that an ablation map that is a Zernike fit of a direct transform of the ocular wavefront phase error is not as efficient in correcting refractive errors of sphere, cylinder, spherical aberration, and coma as when the same Zernike coefficients are applied to a phase plate, with statistically significant improvements from 2% to 6%.

Computer Simulation↗

Functional innervation in tissue engineered models for in vitro study and testing purposes.

The biotechnology industry is rapidly expanding and the emerging field of tissue engineering is projected to have a high impact in the near future. Recently the field of cellular, drug, and prosthetic delivery has melded with the field of tissue engineering to make simulated tissues. In addition to their roles as tissue substitutes for transplantation, these simulated tissues may provide more accurate models and environments for toxicology testing and the study of peripheral nerves. The current study demonstrates the importance of innervation, in general, for the function of engineered tissues. We observe that the presence of nerves in a tissue engineered (TE) human cornea model enhances the growth of the epithelium and the formation of its protective mucin layer. Innervation also confers protection to the epithelium from chemical insult, as determined by the level of post-treatment epithelial cell death. We demonstrate differential responses of the nerves to chemical stimuli by changes in intracellular sodium as measured by 2-photon microscopy. The 2-photon imaging techniques also allow for the visualization and study of the fine sensory axon fibers within the 3-dimensional tissue. This work demonstrates a role for innervation in the protective quality and function of the engineered tissue, and the potential to use the nerves themselves as indicators of the severity of an insult. These results are important to consider for the development of any optimized TE models for in vitro study and testing purposes.

Animals↗

Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation.

Our objective was to determine whether key properties of extracellular matrix (ECM) macromolecules can be replicated within tissue-engineered biosynthetic matrices to influence cellular properties and behavior. To achieve this, hydrated collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and tested on a corneal model. The structural and immunological simplicity of the cornea and importance of its extensive innervation for optimal functioning makes it an ideal test model. In addition, corneal failure is a clinically significant problem. Matrices were therefore designed to have the optical clarity and the proper dimensions, curvature, and biomechanical properties for use as corneal tissue replacements in transplantation. In vitro studies demonstrated that grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels promoted epithelial stratification and neurite in-growth. Implants into pigs' corneas demonstrated successful in vivo regeneration of host corneal epithelium, stroma, and nerves. In particular, functional nerves were observed to rapidly regenerate in implants. By comparison, nerve regeneration in allograft controls was too slow to be observed during the experimental period, consistent with the behavior of human cornea transplants. Other corneal substitutes have been produced and tested, but here we report an implantable matrix that performs as a physiologically functional tissue substitute and not simply as a prosthetic device. These biosynthetic ECM replacements should have applicability to many areas of tissue engineering and regenerative medicine, especially where nerve function is required.

Animals↗

Innervated human corneal equivalents as in vitro models for nerve-target cell interactions.

A sensory nerve supply is crucial for optimal tissue function. However, the mechanisms for successful innervation and the signaling pathways between nerves and their target tissue are not fully understood. Engineered tissue substitutes can provide controllable environments in which to study tissue innervation. We have therefore engineered human corneal substitutes that promote nerve in-growth in a pattern similar to in vivo re-innervation. We demonstrate that these nerves (a) are morphologically equivalent to natural corneal nerves; (b) make appropriate contact with target cells; (c) can generate action potentials; (d) respond to chemical and physical stimuli; and (e) play an important role in the overall functioning of the bioengineered tissue. This model can be used for studying the more general topics of nerve ingrowth or regeneration and the interaction between nerves and their target cells and, more specifically, the role of nerves in corneal function. This model could also be used as an in vitro alternative to animals for safety and efficacy testing of chemicals and drugs.

Action Potentials↗

Increased disk size in glaucomatous eyes vs normal eyes in the Reykjavik eye study.

PURPOSE: To evaluate the use of disk diameter as an indicator in the identification of glaucomatous optic neuropathy. METHODS: We evaluated all available stereofundus photographs for 1,040 right eyes obtained in the Reykjavik Eye Study. Horizontal and vertical disk diameters were determined in a masked manner by a glaucoma specialist (K.F.D.). All disk diameters were corrected for refractive error. RESULTS: There were significant differences (P <.05) between the corrected vertical disk diameters of normal subjects (0.189 +/- 0.018 inches) and those suspected of having glaucoma (0.202 +/- 0.020 inches) as well as between the normal and the glaucoma groups (0.206 +/- 0.029 inches). The corrected horizontal measurement showed the same pattern. CONCLUSIONS: In the Reykjavik Eye Study, optic disks meeting structural criteria for glaucoma are significantly larger than normal nerves.

Glaucoma, Open-Angle↗

Hemodialysis monitoring in whole blood using transmission and diffuse reflection spectroscopy: A pilot study.

Visible and near infrared transmission and diffuse reflection spectroscopy were used to monitor changes in whole blood resulting from hemodialysis treatment for end-stage renal disease. Blood samples from 8 patients on chronic hemodialysis therapy were measured in the 500- to 1700-nm wavelength range immediately before and after a single treatment. Principal component scores characteristic of each spectrum were derived, and mean pre- and posttreatment scores of the first principal component indicated a significant treatment-dependent change in both optical transmission (P = 0.004) and diffuse reflection (P < 0.001). Significant treatment-induced change persisted (P < 0.05) when the first four principal components were used to account for >97% of the treatment-dependent spectral variation. Some blood spectral changes expressed in terms of difference spectra (posttreatment - pretreatment) were consistent with standard clinical indicators of weight reduction, urea reduction, and potassium change, with probable origins at a molecular level. The results indicate the feasibility of using optical transmission and diffuse reflection spectroscopy to characterize clinically relevant blood changes for the future development of more comprehensive indicators of hemodialysis efficacy and long-term clinical outcomes. Moreover, the optical techniques employed are adaptable for potential online monitoring of blood changes during the hemodialysis treatment.

Adult↗