Article

Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision.

Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 08/2006; 103(30):11405-10. DOI: 10.1073/pnas.0506112103
Source: PubMed

ABSTRACT Transparency of the cornea, the window of the eye, is a prerequisite for vision. Angiogenesis into the normally avascular cornea is incompatible with good vision and, therefore, the cornea is one of the few tissues in the human body where avascularity is actively maintained. Here, we provide evidence for a critical mechanism contributing to corneal avascularity. VEGF receptor 3, normally present on lymphatic and proliferating blood vascular endothelium, is strongly constitutively expressed by corneal epithelium and is mechanistically responsible for suppressing inflammatory corneal angiogenesis.

1 Bookmark
 · 
138 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose. To evaluate antiangiogenic effect of local use of bevacizumab (anti-VEGF antibody) in patients with corneal neovascularization. Methods. Patients were divided into two groups. All patients suffered from some form of corneal neovascularization (NV). Patients in group A received 0.2-0.5 mL of bevacizumab solution subconjunctivally (concentration 25 mg/mL) in a single dose. Group A included 28 eyes from 27. Patients in group B applied bevacizumab eye drops twice daily (concentration 2.5 mg/mL) for two weeks. Group B included 38 eyes from 35 patients. We evaluated the number of corneal segments affected by NV, CDVA, and the incidence of complications and subjective complaints related to the treatment. The minimum follow-up period was six months. Results. By the 6-month follow-up, in group A the percentage reduction of the affected peripheral segments was 21.6% and of the central segments was 9.6%; in group B the percentage reduction of the central segments was 22.7% and of the central segments was 38.04%. In both groups we noticed a statistically significant reduction in the extent of NV. Conclusion. The use of bevacizumab seems to be an effective and safe method in the treatment of corneal neovascularization, either in the subconjunctival or topical application form.
    Journal of Ophthalmology 01/2014; 2014:178132. · 1.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The VEGF-A family plays a crucial role in the induction of pathological corneal neovascularization. The role of the different VEGF-A isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic therapies in the eye and other organs inhibit all VEGF-A isoforms, and have effects on both blood and lymphatic vessels. Here we investigate whether selective targeting of the isoform VEGF 165 is able to inhibit corneal lymphangiogenesis under inflammatory conditions. The mouse model of suture-induced corneal neovascularization was used to assess the antihem- and antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic endothelial cells (BEC/LEC) via a cell-proliferation assay. Pegaptanib significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than LECs. Targeting VEGF-A 165 significantly inhibits hem- but not lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable for lymphangiogenesis, at least in the inflamed cornea.
    Albrecht von Graæes Archiv für Ophthalmologie 04/2014; · 1.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose To test whether subconjunctival cyclosporine A (CsA) implants affect the incidence and the degree of corneal neovascularization occurring after penetrating keratoplasty. Design Prospective, randomized, multicenter, controlled phase 2/3 clinical trial. The study comprised 43 trial sites in Germany, India, and the United States. Participants Enrolled patients (n = 97) were randomized to 1 of 3 groups: treatment group A (n = 36), treatment group B (n = 40), and the control group (n = 21). Methods Patients from each group received either of 2 doses of subconjunctival CsA (group A, low-dose CsA; group B, high-dose CsA) or placebo (carrier only) implants at the time of high-risk penetrating keratoplasty. Main Outcome Measures The incidence and degree of corneal neovascularization occurring after penetrating keratoplasty were evaluated in a substudy (LX201-01 study: NCT00447187). A web-based image upload system was developed. Standardized digital slit-lamp pictures were quantitatively and objectively evaluated using CellˆF morphometry software. Results No statistically significant difference in incidence and degree of corneal neovascularization developing after penetrating keratoplasty was found between treatment groups and placebo group. Mean corneal neovascularization area at week 52 (visit 12) was 2.32±1.79% in treatment group A versus placebo (2.79±2.11%; P = 0.45) and 2.74±2.22% in treatment group B versus placebo (2.79±2.11%; P = 0.94). Conclusions High-dose subconjunctival CsA implants do not significantly affect corneal neovascularization after high-risk penetrating keratoplasty. This suggests that local CsA has negligible antiangiogenic effects in the human cornea, at least in the transplant setting.
    Ophthalmology 09/2014; · 5.56 Impact Factor

Full-text (2 Sources)

Download
52 Downloads
Available from
May 27, 2014