Corneal blindness and xenotransplantation

Lamm, Vladimir; Hara, Hidetaka; Mammen, Alex; Dhaliwal, Deepinder K.; Cooper, David K. C.

doi:10.1111/xen.12082

Cited by 75 publications

(60 citation statements)

References 146 publications

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“…272,273 Bullous keratopathy, or corneal edema, is a leading indication for PKP and corneal transplantation in general. 271 With advancement in the field of corneal surgery, IVCM provides a sensitive in vivo tool to provide cellular monitoring of the graft for best visual and surgical outcomes. 274,275 …”

Section: Corneal Nerve Alterations After Corneal Surgerymentioning

confidence: 99%

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

2017

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In vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in vivo imaging of the cornea with images comparable to that of ex vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, and proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases.

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Section: Corneal Nerve Alterations After Corneal Surgerymentioning

confidence: 99%

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

2017

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“…Porcine corneas are one possibility (1–4). Previously, Pan et al, showed that corneas from Wuzhishan miniature pigs survived for 6 months in rhesus monkeys treated with local corticosteroids (5).…”

Section: Introductionmentioning

confidence: 99%

Development of retrocorneal membrane following pig‐to‐monkey penetrating keratoplasty

Lee

Mammen

Dhaliwal

et al. 2016

Xenotransplantation

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Introduction Recent reports of long-term survival after wild-type (WT) pig-to-monkey corneal xenotransplantation are encouraging. We experienced the rapid development of retrocorneal membranes, a rare complication after corneal allotransplantation (though seen in infants and young children). The original specific aim of the study was to determine the factors associated with successful (young) pig corneal transplantation in monkeys. However, when it was obvious that retrocorneal membranes rapidly developed, our aims became to determine the factors involved in its development after both WT and GE pig corneal xenotransplantation and to investigate the characteristics of the retrocorneal membrane. Methods Rhesus monkeys were recipients of penetrating keratoplasty using WT and GE pigs (n=2, respectively, 1–3 months-old). Local/systemic steroids were administered for 3 months. Grafts were evaluated by slit-lamp for corneal transparency, edema, and neovascularization. Hematoxylin and eosin, Masson trichrome staining, and immunohistochemical analysis were performed. Gal staining was also carried out to distinguish the origin of the membrane. Results All penetrating keratoplasty recipients developed fibrous retrocorneal membranes in the early post-transplantation period, regardless of whether the graft was from a WT or GE pig. There were no features of rejection, with no cell infiltrate in the graft or anterior chamber during the 3 months follow-up. There was no difference in the clinical course between the two groups (WT or GE corneas). Immunohistochemistry indicated that the retrocorneal membranes were CK-negative, α-SMA-positive, and vimentin-positive, suggesting that they were of fibrous (keratocytic) origin. Also, the membrane was Gal positive, suggesting that it is derived from pig cornea. Conclusions Following pig-to-monkey corneal xenotransplantation, we report that retrocorneal membranes are derived from donor pig keratocytes. Prevention of retrocorneal membranes will be necessary to achieve successful corneal xenotransplantation.

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“…Corneal blindness, for which corneal transplantation is the only treatment, has a devastating global impact . The shortage of human donor corneas is an emerging issue that has stimulated interest in corneal xenotransplantation, with porcine corneas being considered a feasible source.…”

Section: Cornea‐specific Considerations For Preparing An Initial Cornmentioning

confidence: 99%