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1.  Spontaneous T cell mediated keratoconjunctivitis in Aire-deficient mice 
The British journal of ophthalmology  2009;93(9):1260-1264.
Patients with autoimmune polyendocrinopathy-candiasis-ectodermal dystrophy (APECED) develop severe keratoconjunctivitis, corneal scarring and visual loss, but the precise pathogenesis is unknown. This study evaluated the ocular surface immune cell environment, conjunctival goblet cell density and response to desiccating environmental stress of the autoimmune regulatory (Aire) gene knockout murine model of APECED.
Aire-deficient and wild type (WT) mice were subjected to desiccating stress from a drafty, low-humidity environment and pharmacological inhibition of tear secretion for 5 days. Immune cell populations (CD4+, CD8+, CD11b+, CD45+) and goblet cell density were measured in ocular surface tissues and meibomian glands, and compared with baseline values.
Greater CD4+ T cell populations were observed in the conjunctival epithelium of Aire-deficient mice (p<0.001) compared with WT. Aire-deficient mice also had greater numbers of CD4+, CD8+, and CD11b+ cells in the peripheral cornea at baseline and following desiccating stress. The meibomian glands of Aire-deficient mice demonstrated greater CD4+, CD8+, CD45+ and CD11b+ cells at baseline (p<0.001) and following desiccating stress. Conjunctival goblet cell density was lower at baseline and following desiccating stress in Aire-deficient compared with WT mice (p<0.001).
Aire-deficiency leads to infiltration of CD4+ and CD8+ T cells on the ocular surface and meibomian glands, which is accompanied by goblet cell loss. Desiccating stress promotes this proinflammatory milieu. Immune-mediated mechanisms play a role in the severe blepharitis and keratoconjunctivitis in the murine model of APECED.
PMCID: PMC3586820  PMID: 19429577
2.  Expression of glial cell-derived neurotrophic factor and its receptor in the stem-cell-containing human limbal epithelium 
The British journal of ophthalmology  2008;92(9):1269-1274.
To evaluate the expression pattern of glial cell line-derived neurotrophic factor (GDNF) with its receptors GDNF family receptor alpha-1 (GFRα-1) and Ret in the human corneal and limbal tissues, as well as in the primary human limbal epithelial cultures (PHLEC).
Expression of GDNF and its receptors, and the co-localisation with stem cell associated and differentiation markers were evaluated by immunofluorescent staining, western blot analysis and real-time PCR in the fresh human corneoscleral tissues, as well as in the PHLEC. Single cell colony-forming and wound-healing assays were also evaluated in PHLEC.
GDNF and GFRα-1 were found to be expressed by a subset of basal cells and co-localised with ATP-binding cassette, subfamily G (WHITE), member 2 (ABCG2) and p63, but not with cytokeratin 3 in the human limbal basal epithelium. In PHLEC, they were expressed by a small population of cells in the less differentiated stage. The GDNF and GFRα-1-positive subpopulations were enriched for the expression of ABCG2 and p63 (p<0.01). Recombinant human GDNF promoted the proliferation and wound healing of epithelial cells in the PHLEC. In contrast, Ret was abundantly located in the human corneal epithelium except for the basal cells of the limbal epithelium.
These findings indicate that GDNF and GFRα-1 may represent a property for the phenotype of human corneal epithelial precursor cells. GDNF may signal independently of Ret through GFRα-1 in the stem cell-containing limbal epithelium.
PMCID: PMC2906381  PMID: 18723744
3.  A simple and evolutional approach proven to recanalise the nasolacrimal duct obstruction 
Chen, D | Ge, J | Wang, L | Gao, Q | Ma, P | Li, N | Li, D-Q | Wang, Z
The British Journal of Ophthalmology  2009;93(11):1438-1443.
To evaluate a new approach of recanalisation of nasolacrimal duct obstruction (RC-NLDO) in the treatment of the nasolacrimal duct obstruction (NLDO) and chronic dacryocystitis.
583 patients with 641 eyes suffering from NLDO and chronic dacryocystitis were enrolled in this study. The RC-NLDO was performed in 506 eyes, with 135 eyes undergoing external dacryocystorhinostomy (EX-DCR) as controls. Patient follow-up for 54 months was evaluated by symptoms, dye disappearance test, lacrimal irrigation and digital subtraction dacryocystogram. The RC-NLDO was also performed in 12 rhesus monkeys for histopathological examination.
The clinical success rates were 93.1% in 506 cases of RC-NLDO and 91.11% in 135 cases of EX-DCR. The success rates for second surgery were achieved in 85.19% on RC-NLDO and 40.0% on EX-DCR. No major intra- or postoperative complications were observed in the RC-NLDO group. The mean operative duration was 12.5 min for RC-NLDO and 40.3 min for EX-DCR (p<0.001). A pathological study in rhesus monkeys demonstrated that the RC-NLDO wounded epithelium in nasolacrimal duct healed completely within 1 month without granulation tissue formation.
The findings demonstrate that the RC-NLDO is a simple and effective approach proven to recanalise the obstructed nasolacrimal duct with a comparable success rate to EX-DCR.
PMCID: PMC2760725  PMID: 19416937

Results 1-3 (3)