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Mannis, M. J.

Publications and source records attributed to Mannis, M. J..

2 recordsLinked to original sources

Oxygen uptake in human donor corneas: the centripetal gradient and its changes in culture and correlation with wounds and aminophylline treatment

Oxygen is a diatomic element abundant in the atmosphere and is essential for homeostatic and metabolic processes within the cornea. The avascular cornea uptakes oxygen from the atmosphere and performs refractory and protective functions that are essential for eyesight. However, the spatial-temporal profile of oxygen uptake (O2U) in human corneas remains uncharacterized in literature. Utilizing the micro optrode technique and donor corneas, we demonstrated that the limbus has a significantly higher O2U than the cornea center, exhibiting a pattern of centripetal gradient of O2U. This pattern is thus conserved in the corneas of mice, rats, non-human primates, and humans, representing a metabolic feature of physiological significance, which may have diagnostic and prognostic value. Being cultured at 37{degrees}C and 5% CO2, this centripetal pattern became more prominent in the first three days, and less so on day 4. The pattern remained in the corneas with injury, increased O2U appears to correlate with wound healing, similar to patterns observed in animal models with a dynamic increase of metabolism in the periphery, followed by the limbus, and subsequent return to baseline. Administration of the drug aminophylline prevented a decrease of O2U at day 4. We conclude that the centripetal pattern of O2U is conserved across species and in the human cornea. Combined, our results suggest the functional and clinical significance of the mesoscopic metabolism pattern for further study and the use of aminophylline as a therapeutic agent to increase O2U and enhance corneal wound healing.

cell biology↗

A Practical and Safe Model of Nitrogen Mustard Injury in Cornea

PurposeSulfur mustard (SM) is an alkylating agent used in warfare and terrorism that inflicts devastating ocular injuries. Although the clinical symptoms are well described, the underlying mechanisms are not fully understood, hindering the development of effective treatments. One major roadblock is the lack of a suitable model due to the extremely hazardous nature of SM, which requires strict safety measures. As a safe and practical alternative, we report a novel model that uses mechlorethamine (nitrogen mustard) gel, an FDA-approved topical chemotherapeutic administered by patients at home. Here we demonstrate its suitability to induce mustard corneal injury in any laboratory. MethodsEx vivo porcine corneas were injured with mechlorethamine gel. Hematoxylin-eosin staining, and immunohistochemistry were performed to evaluate histopathology of SM-like corneal injuries: epithelium thickness and stromal separation, keratocyte and inflammatory cell counts, and expression of inflammation and fibrosis markers. ResultsThis model showed the characteristic histopathology and expression of cyclooxygenase-2 (inflammation) and fibronectin-1 (fibrosis), which were consistent with other well-established SM-like corneal injury models. ConclusionGiven its ease of implementation and safety, this mechlorethamine model could be used to study the full course of mustard corneal injuries. This model would greatly facilitate mustard injury research, shedding light on new knowledge that would increase our understanding of mustard ocular injuries while investigating novel therapeutics. Translational relevancethis model will allow safe evaluation of SM-like corneal injuries within 24 hours, facilitating the identification of early/new molecules that might help to develop novel treatments which could be readily translated into the clinic.

pharmacology and toxicology↗