Abstract
Purpose :
A healthy human cornea is clear and devoid of vasculature. However, as a result of infection or trauma, the cornea can become opaque with scarring and pronounced neovascularization, requiring a corneal transplant for visual rehabilitation. Patients with vascularized corneal beds are at high risk for graft rejection and failure. There are few published reports describing neovascularization associated with infection in the human cornea. We hypothesize pro-angiogenic factors that drive neovascularization (defined as the genesis of blood and/or lymphatic vessels) is distinct depending on the cause of insult (infection vs trauma). To test this hypothesis, we evaluated >90 cornea buttons removed from patients undergoing corneal transplants for infectious/inflammatory (I/I) conditions and compared to non-infectious/non-infectious(NI/NI) and non-infectious/inflammatory(NI/I) conditions.
Methods :
Cornea buttons obtained within 4 hours of surgical explantation were processed for subsequent analysis for pro-angiogenic gene expression by PrimePCR, cytokine and pro-angiogenic protein expression by suspension array, leukocyte infiltration by flow cytometry, and/or detection of blood (CD31+) and lymphatic (LYVE-1+) vessel by immunohistochemical stain and confocal analysis. Due to limited specimen, each cornea sample was not investigated for all four parameters under study.
Results :
Gene array analysis of NI/NI (n=6), NI/I (n=8), and I/I (n=5) cohorts found that CCL21 expression was elevated (p<.05) in the I/I group compared to the other two cohorts and platelet-derived growth factor A expression was reduced (p<.01) in the NI/I and I/I cohorts compared to the NI/NI control. At the protein level, IL-1β, IL-8, TNF-α, VEGF-A, VEGF-C, and CXCL10 were elevated (p<.05) in the I/I cohort (n=14) compared to the NI/I (n=20) and NI/NI (n=7) cohorts. It was also noted the absolute number of CD8+ T cells residing in the cornea of the I/I (n=4) group was elevated (p<.05) compared to the NI/I (n=10) and NI/NI (n=7) groups.
Conclusions :
These results suggest a pro-angiogenic profile in the scarred corneas of patients diagnosed with an infectious/inflammatory etiology compared to those with a non-infectious/inflammatory mechanism that may contribute to neovascularization.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.