Preliminary findings in corneal allograft rejection in patients with keratoconus

Hargrave, Sylvia L.; Chu, Yilin; Mendelblatt, David; Mayhew, Elizabeth; Niederkorn, Jérry Y.

doi:10.1016/s0002-9394(02)02055-x

Cited by 34 publications

(26 citation statements)

References 25 publications

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“…Ϫ/Ϫ mice, or mice depleted of IL-12 with mAbs (9,12,21,22), which differ from the present atopy model in that the mice are incapable of generating Th1 immune responses, a scenario that is unlikely to occur in human subjects. By contrast, the present atopy model mimics a significant category of human corneal transplant recipients.…”

Section: Presence Of Th1 and Th2 Cells In Rejected Corneal Allograftsmentioning

confidence: 76%

“…Previous studies involving corneal transplantation in Th2-deviated hosts have produced conflicting results ranging from allograft acceptance to complete rejection (3,11). Clinical observations indicate that patients with severe ocular allergies are at a higher risk of corneal transplant rejection (12). In this study, we examined corneal allograft rejection in a mouse model of atopic conjunctivitis involving sensitization and topical challenge with short ragweed pollen, a common allergen in humans (13).…”

mentioning

confidence: 99%

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Cutting Edge: Atopy Promotes Th2 Responses to Alloantigens and Increases the Incidence and Tempo of Corneal Allograft Rejection

Beauregard

Stevens

Mayhew

et al. 2005

The Journal of Immunology

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A large body of evidence suggests that corneal allograft rejection is mediated by a type 1 Th cell response and that deviation toward type 2 immunity favors graft survival. However, clinical observations indicate that patients with severe ocular allergies have increased risk of corneal allograft rejection. We used a mouse model of atopic conjunctivitis to evaluate the effects of Th2 immune deviation on corneal allograft survival and possible mechanisms of graft rejection. Our results reveal the following novel findings: 1) atopic conjunctivitis promotes systemic Th2 immune responses to corneal graft donor alloantigens; 2) corneal allografts in atopic host eyes have an increased incidence and swifter tempo of rejection; 3) increased rejection is associated with alterations in systemic T cell-mediated responses to donor alloantigens; and 4) corneal allograft rejection in atopic hosts does not require the direct involvement of infiltrating eosinophils.

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Section: Presence Of Th1 and Th2 Cells In Rejected Corneal Allograftsmentioning

confidence: 76%

mentioning

confidence: 99%

Cutting Edge: Atopy Promotes Th2 Responses to Alloantigens and Increases the Incidence and Tempo of Corneal Allograft Rejection

Beauregard

Stevens

Mayhew

et al. 2005

The Journal of Immunology

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“…6 Furthermore, the presence of atopic disease is associated with more rapid corneal thinning, the need for earlier corneal grafting and a higher incidence of postgraft immunologic complications. 7 Despite this known link between atopy and corneal degeneration, current international clinical guidelines relating to the management of childhood atopy 8 do not include recommendations for ocular health evaluation.…”

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confidence: 99%

The Necessity for Ocular Assessment in Atopic Children: Bilateral Corneal Hydrops in an 8 Year Old

Downie

2014

Pediatrics

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Acute corneal hydrops is a rare complication of advanced corneal ectasia. This case report describes the clinical course of a child with severe atopy and no previous ocular examination who developed bilateral, acute corneal hydrops, secondary to keratoconus, by 8 years of age. The report demonstrates the rapidity of progression in the pediatric phenotype of the disease. This case also provides an important clinical lesson in highlighting the necessity for children with atopy to be referred for comprehensive ophthalmic examination, even in the apparent absence of visual symptoms, to ensure the timely diagnosis and management of any atopy-associated ocular disease. Prompt referral is particularly essential for pediatric corneal ectasia, in which the rapidity of progression may preclude stabilizing treatments, such as corneal collagen cross-linking, and result in significant childhood visual impairment, as was the case for this child. This case demonstrates the potential for significant ocular involvement in atopic children and identifies scope to enhance current international clinical guidelines relating to the management of childhood atopy through the inclusion of ocular screening for associated disease.

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“…Eosinophils might induce damage to the cornea by release of cytotoxic arginine-rich proteins such as eosinophil peroxidase, which has been implicated in the development of corneal ulcers (54). Niederkorn and colleagues (55) have recently shown increased numbers of eosinophils in rejected human corneal grafts from atopic patients with keratoconus. We hypothesize that eosinophil degranulation within a corneal graft will fuel inflammation and exacerbate a rejection response.…”

Section: Discussionmentioning

confidence: 99%

Prolongation of Sheep Corneal Allograft Survival by Transfer of the Gene Encoding Ovine IL-12-p40 but Not IL-4 to Donor Corneal Endothelium

Klebe¹,

Coster²,

Sykes³

et al. 2005

The Journal of Immunology

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Immunological rejection is the major cause of human corneal allograft failure. We hypothesized that local production of IL-4 or the p40 subunit of IL-12 (p40 IL-12) by the grafted cornea might prolong allograft survival. Replication-deficient adenoviral vectors encoding ovine IL-4 or p40 IL-12 and GFP were generated and used to infect ovine corneas ex vivo. mRNA for each cytokine was detected in infected corneas, and the presence of secreted protein in corneal supernatants was confirmed by bioassay (for IL-4) or immunoprecipitation (for p40 IL-12). Sheep received uninfected or gene-modified orthotopic corneal allografts. Postoperatively, untreated corneas (n = 13) and corneas expressing GFP (n = 6) were rejected at a median of 21 and 20 days, respectively. Corneas expressing IL-4 (n = 6) underwent rejection at 18.5 days (p > 0.05 compared with controls) and histology demonstrated the presence of eosinophils. In contrast, corneas expressing p40 IL-12 (n = 9) showed prolonged allograft survival (median day to rejection = 45 days, p = 0.003). Local intraocular production of p40 IL-12 thus prolonged corneal graft survival significantly, but local production of the prototypic immunomodulatory cytokine IL-4 induced eosinophilia, inflammation, and rejection. These findings have important implications for the development of novel strategies to improve human corneal graft survival.

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Preliminary findings in corneal allograft rejection in patients with keratoconus

Cited by 34 publications

References 25 publications

Cutting Edge: Atopy Promotes Th2 Responses to Alloantigens and Increases the Incidence and Tempo of Corneal Allograft Rejection

Cutting Edge: Atopy Promotes Th2 Responses to Alloantigens and Increases the Incidence and Tempo of Corneal Allograft Rejection

The Necessity for Ocular Assessment in Atopic Children: Bilateral Corneal Hydrops in an 8 Year Old

Prolongation of Sheep Corneal Allograft Survival by Transfer of the Gene Encoding Ovine IL-12-p40 but Not IL-4 to Donor Corneal Endothelium

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