Abstract
Purpose :
Asymmetrical neovascularization has been reported in the pathogenesis of multiple ocular conditions such as pterygium and pinguecula. Here, we investigated whether distribution of ocular surface mast cells are functionally associated with angiogenic response.
Methods :
Corneal neovascularization was induced by placing a single figure-8 intrastromal suture on the nasal or temporal side of the cornea using 11-0 nylon suture. Growth of blood vessels were observed clinically using a slit-lamp biomicroscope and at the molecular level by immunohistochemistry (IHC) analysis of CD31+ vascular endothelial cells in harvested corneas on day 7 post-suture. Distribution and activation of mast cells in the nasal and temporal corneas were evaluated by IHC analysis of avidin stained corneas and by quantification of tryptase and β-hexosaminidase levels in tear and corneal lysates. Mast cell deficient cKitw-sh mice and cromolyn (2% in PBS) treated mice were used to study the effect of mast cell distribution on asymmetrical corneal angiogenesis.
Results :
A nasally placed suture resulted in more extensive corneal neovascularization compared to one placed temporally, as evidenced by slit lamp (p=0.01) and IHC analysis (p=0.04). IHC analysis showed a 2-fold increase in number of avidin+ mast cells in the nasal cornea compared to the temporal cornea. Moreover, 4.3-fold increase in tryptase levels and 2.1-fold increase in β-hexosaminidase levels were observed following suture placement on the nasal side, compared to the naive cornea. Suture on the temporal side resulted in significantly less increase in tryptase (1.4-fold (p=0.0002)) and β-hexosaminidase levels (1.1-fold (p=0.006)). Mast cell deficiency and cromolyn-mediated inhibition of mast cell activation abrogated the disproportionate growth of blood vessels, resulting in comparable nasal and temporal neovascularization, as evidenced by slit-lamp and IHC.
Conclusions :
Our novel findings demonstrate that the spatial distribution and function of mast cells regulate pathological angiogenesis.
This is a 2021 ARVO Annual Meeting abstract.