The effect of perioperative allergic conjunctivitis on corneal lymphangiogenesis after corneal transplantation

Flynn, Tom; Ohbayashi, Masaharu; Dawson, Maria; Larkin, Frank; Ono, Santa Jeremy

doi:10.1136/bjo.2010.201939

Cited by 11 publications

(10 citation statements)

References 33 publications

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“…For example, patients who suffer from ocular allergy are at an elevated risk for immune rejection in corneal transplantation, which has been proven in mice as well. 48,49 Furthermore, in the mouse model of corneal allotransplantation, Flynn et al 49 showed that perisurgical ocular allergy was associated with augmented corneal LA, 49 and Dietrich et al 10 reported that in mice the presence of corneal LA was a risk factor for corneal allograft rejection. Thus, further studies in humans are warranted to validate the presence of corneal LA in ocular and whether such activity 4.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Corneal Lymphangiogenesis in a Mouse Model of Allergic Eye Disease

Lee

Hos

Blanco

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The contribution of lymphangiogenesis (LA) to allergy has received considerable attention and therapeutic inhibition of this process via targeting VEGF has been considered. Likewise, certain inflammatory settings affecting the ocular mucosa can trigger pathogenic LA in the naturally avascular cornea. Chronic inflammation in allergic eye disease (AED) impacts the conjunctiva and cornea, leading to sight threatening conditions. However, whether corneal LA is involved is completely unknown. We addressed this using a validated mouse model of AED.METHODS. Allergic eye disease was induced by ovalbumin (OVA) immunization and chronic OVA exposure. Confocal microscopy of LYVE-1-stained cornea allowed evaluation of corneal LA, and qRT-PCR was used to evaluate expression of VEGF-C, -D, and -R3 in these mice. Administration of VEGF receptor (R) inhibitor was incorporated to inhibit corneal LA in AED. Immune responses were evaluated by in vitro OVA recall responses of T cells, and IgE levels in the serum. RESULTS.Confocal microscopy of LYVE-1-stained cornea revealed the distinct presence of corneal LA in AED, and corroborated by increased corneal expression of VEGF-C, -D, and -R3. Importantly, prevention of corneal LA in AED via VEGFR inhibition was associated with decreased T helper two responses and IgE production. Furthermore, VEGFR inhibition led a significant reduction in clinical signs of AED.CONCLUSIONS. Collectively, these data reveal that there is a distinct involvement of corneal LA in AED. Furthermore, VEGFR inhibition prevents corneal LA and consequent immune responses in AED.

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Section: Discussionmentioning

confidence: 99%

Involvement of Corneal Lymphangiogenesis in a Mouse Model of Allergic Eye Disease

Lee

Hos

Blanco

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…Compared with NRPK, eyes that underwent an HRPK exhibited significantly higher levels of chemokines for NV induction in the early prerejection postoperative period. 29 Accordingly, there are several published reports that insist on the early treatment of antiinflamamatory agents in HRPK. 6,16,17,22 Regimens that result in significant degrees of angiostasis, but are delayed in onset, do not have an appreciable effect on the capacity of eye to promote deviant immunity.…”

Section: Discussionmentioning

confidence: 99%

Presurgical Corticosteroid Treatment Improves Corneal Transplant Survival in Mice

Kim

Choi

Uehara

et al. 2013

Cornea

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Purpose To examine the effects of presurgical corticosteroid treatment for normal-risk penetrating keratoplasty (NRPK), high-risk penetrating keratoplasty (HRPK), and high-risk penetrating keratoplasty plus lensectomy. Methods We used 3 corneal transplantation models (NRPK, HRPK, and high-risk penetrating keratoplasty plus lensectomy). For each model, we tried to compare the effect of corticosteroid treatment according to different timetables as follows: The first trial began with a corticosteroid injection given 2 weeks before the PK and continued until 4 weeks after the PK (group 1). The second trial started with a corticosteroid injection given on the day of the PK and continued for 4 weeks after the PK (group 2). The third trial started with a corticosteroid injection administered on the day of the PK and continued for 8 weeks after the PK (group 3). After harvesting and immunostaining of corneas, graft survival, neovascularization (NV), and lymphangiogenesis (LY) were compared among the groups. A P value <0.05 was considered as being statistically significant. Results With respect to graft survival, group 1 had improved graft survival compared with that of group 3 in the HRPK model (P = 0.025). In all the 3 PK models, groups 2 and 3 demonstrated a similar graft survival (P > 0.05). With respect to NV and LY, in NRPK, group 1 showed less NV than did group 2 (P < 0.001) and group 3 (P = 0.016). In HRPK, group 1 also demonstrated less NV and LY than did group 3 (P = 0.045 and 0.044, respectively). Conclusions The initiation time point of the corticosteroid treatment is important for graft survival. Corticosteroid pretreatment is an effective means to increase graft survival for HRPK and to decrease NV and LY for both NRPK and HRPK.

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“…189 The immune response against allogeneic corneal tissue is also intensified in the presence of allergic conjunctivitis, which has been shown to have corneal lymphangiogenesis involvement. 190; 191 …”

Section: Diseases Associated With Corneal Lymphangiogenesismentioning

confidence: 99%

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions

Yang

Walia

Huang

et al. 2016

Survey of Ophthalmology

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A major focus of cancer research for several decades has been understanding the ability of tumors to induce new blood vessel formation, a process known as angiogenesis. Unfortunately, only limited success has been achieved in the clinical application of angiogenesis inhibitors. We now know that lymphangiogenesis, the growth of lymphatic vessels, likely also plays a major role in tumor progression. Thus, therapeutic strategies targeting lymphangiogenesis or both lymphangiogenesis and angiogenesis may represent promising approaches for treating cancer and other diseases. Importantly, research progress toward understanding lymphangiogenesis is significantly behind that related to angiogenesis. A PubMed search of ‘angiogenesis’ returns nearly 80,000 articles, whereas a search of ‘lymphangiogenesis’ returns approximately 2,635 articles. This stark contrast can be explained by the lack of molecular markers for identifying the invisible lymphatic vasculature that persisted until less than two decades ago combined with the intensity of research interest in angiogenesis during the past half-century. Still, significant strides have been made in developing strategies to modulate lymphangiogenesis, largely using ocular disease models. Here, we review the current knowledge of lymphangiogenesis in the context of knockout models, ocular diseases, the biology of activators and inhibitors, and the potential for therapeutic interventions targeting this process.

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The effect of perioperative allergic conjunctivitis on corneal lymphangiogenesis after corneal transplantation

Cited by 11 publications

References 33 publications

Involvement of Corneal Lymphangiogenesis in a Mouse Model of Allergic Eye Disease

Involvement of Corneal Lymphangiogenesis in a Mouse Model of Allergic Eye Disease

Presurgical Corticosteroid Treatment Improves Corneal Transplant Survival in Mice

Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions

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