Transplantation of cryopreserved human corneas in a xenograft model

Ohno, Kenji; Nelson, Leif R.; Mitooka, Katsuya; Bourne, William M.

doi:10.1016/s0011-2240(02)00016-0

Cited by 30 publications

(16 citation statements)

References 16 publications

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“…[26], [27] In addition, cats have been used previously to study corneal disease including in vivo models of Fuchs’ endothelial dystrophy (Brunette I. IOVS 2012; ARVO E-Abstract 330 and Haydari MN, et al IOVS 2012; ARVO E-Abstract 3640). [28], [29] The cat model has also been used to further our understanding of ophthalmic surgical interventions, including keratoplasty [30]–[34]. Histological correlates have demonstrated keratocyte activation and apoptosis adjacent to wounds following penetrating keratoplasty.…”

Section: Discussionmentioning

confidence: 99%

Keratocyte Apoptosis and Not Myofibroblast Differentiation Mark the Graft/Host Interface at Early Time-Points Post-DSAEK in a Cat Model

et al. 2013

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PurposeTo evaluate myofibroblast differentiation as an etiology of haze at the graft-host interface in a cat model of Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK).MethodsDSAEK was performed on 10 eyes of 5 adult domestic short-hair cats. In vivo corneal imaging with slit lamp, confocal, and optical coherence tomography (OCT) were performed twice weekly. Cats were sacrificed and corneas harvested 4 hours, and 2, 4, 6, and 9 days post-DSAEK. Corneal sections were stained with the TUNEL method and immunohistochemistry was performed for α-smooth muscle actin (α-SMA) and fibronectin with DAPI counterstain.ResultsAt all in vivo imaging time-points, corneal OCT revealed an increase in backscatter of light and confocal imaging revealed an acellular zone at the graft-host interface. At all post-mortem time-points, immunohistochemistry revealed a complete absence of α-SMA staining at the graft-host interface. At 4 hours, extracellular fibronectin staining was identified along the graft-host interface and both fibronectin and TUNEL assay were positive within adjacent cells extending into the host stroma. By day 2, fibronectin and TUNEL staining diminished and a distinct acellular zone was present in the region of previously TUNEL-positive cells.ConclusionsOCT imaging consistently showed increased reflectivity at the graft-host interface in cat corneas in the days post-DSAEK. This was not associated with myofibroblast differentiation at the graft-host interface, but rather with apoptosis and the development of a subsequent acellular zone. The roles of extracellular matrix changes and keratocyte cell death and repopulation should be investigated further as potential contributors to the interface optical changes.

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Section: Discussionmentioning

confidence: 99%

Keratocyte Apoptosis and Not Myofibroblast Differentiation Mark the Graft/Host Interface at Early Time-Points Post-DSAEK in a Cat Model

et al. 2013

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“…Diverse cell types often demonstrate sensitivity differences to cold injury. The exploitation of these differences for therapeutic purposes, whether for ablation or preservation of cells and tissues, depends on these dichotomous responses [9,13,60,76,91,118,120,128]. Prostate cancer cells have demonstrated distinct freeze susceptibilities correlated to the androgen receptor expression [62].…”

Section: Cryoablative Injury Mechanismsmentioning

confidence: 99%

Mechanisms of cryoablation: Clinical consequences on malignant tumors

et al. 2014

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While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer that, while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity, we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer.

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“…Finally, short term human-to-cat corneal xenografts are well tolerated. 53,54 Additional improvements to this model could include a longer follow-up. A 7-day follow-up period was chosen here to avoid xenograft rejection.…”

Section: Characteristics Of the Proposed Fecd Modelmentioning

confidence: 99%