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Makambo Tshionyi, Elizabeth Shay, Elisa Lunde, Amy Lin, Kyu-Yeon Han, Sandeep Jain, Jin-Hong Chang, Dimitri Azar; Prevalence and Distribution of Hemangiogenesis and Lymphangiogenesis in Pathologic Corneas. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2017. doi: https://doi.org/.
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We characterized the prevalence and distribution of hemangiogenesis (HA) and lymphangiogenesis (LA) in human corneal specimens exhibiting 13 underlying pathologies.
Human corneal specimens collectively exhibiting Acanthamoeba keratitis, bullous keratopathy, chronic keratitis, corneal scarring, Fuchs’ dystrophy, fungal keratitis, graft failure, graft rejection, herpes simplex virus keratitis, inflammatory pannus, keratoconus, pterygium, and ulcerative keratitis with perforation were obtained from consenting subjects (n=2 or n=3 for each pathology; total sample size, n=35). The pathologic specimens were stained with hematoxylin and Eosin (H&E) to determine the presence or absence of (i) corneal neovascularization, as well as (ii) comparatively superficial or deep stromal distribution of neovascularization (NV). Immunohistochemical staining was then performed to differentiate the prevalence and distribution of HA (positive for CD31) from that of LA (positive for lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1)).
The double negative (CD31+/LYVE-1+) phenotype, indicating the absence of NV, was exhibited by 21 specimens (60%). The mixed phenotype (CD31+/LYVE-1-), indicating the presence of HA and the absence of LA, was exhibited by 12 specimens (34%). The double-positive (CD31+/LYVE-1+) phenotype, indicating the presence of both HA and LA, was exhibited by two specimens (6%). Notably, the CD31+/LYVE-1+ mixed phenotype, indicating the presence of LA and the absence of HA, was not detected amongst the specimens. Comparatively deep stromal NV exhibited in a 4:3 ratio to superficial stromal NV.
The double-negative phenotype was more prevalent in corneal specimens exhibiting non-inflammatory pathologies; the ratio of the double-negative phenotype to the combined neovascular phenotypes (i.e., CD31+ or LYVE-1+) was 3:2. Among the neovascular phenotypes, HA was seven times more prevalent than was LA. Specimens exhibiting LA presented only with the double-positive phenotype. NV was predominantly detected in the deep stromal, rather than the superficial stromal, tissue layer. Our results suggest potential therapeutic utility of targeting anti-neovascular therapies specifically to corneal HA, LA, or mixed pathology.
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