NEUROTROPHIC FACTOR MODULATION OF CORNEAL ENDOTHELIUM

点击翻译按钮获取中文摘要

The corneal endothelium functions as a barrier to fluid movement into the cornea and maintains the transparency of the cornea. Human corneal endothelial cells (CEC), like neuronal cells, essentially do not regenerative in vivo. Just as the survival of neurons is promoted by neurotrophic factors, the survival of CEC may also be promoted by trophic factors. Ciliary neurotrophic factor (CNTF) was discovered and originally isolated from an extract of eye tissues consisting of ciliary body, iris, and choroid. CNTF induces in neurons the expression of the gene for VIP, a neuropeptide that also shows neurotrophic activities. In donor human, preliminary studies showed that VIP-immunoreactivities and VIP mRNA are present in the CEC, that both CNTF and VIP receptors are expressed in CEC, that CNTF is expressed in the cornea, and that the VIP-immunoreactivities are up- regulated in CNTF- treated human corneas in organ cultures. Further, preliminary studies of the bovine cornea showed 1) the presence of CNTF receptor and VIP mRNA in the CEC, 2) VIP treatment helped the CEC in trephined cornea buttons to survive subsequent hydrogen peroxide treatment, and 3) VIP helped to preserve the hexagonal cell borders of the CEC in cornea organ cultures. Our long-term goal is to demonstrate that CNTF and VIP are trophic factors of human CEC capable of 1) prolonging the duration of preservation of corneas for transplantation and 2) maintaining the integrity. Of transplanted corneas in recipient eyes. Our specific aims are: To test the hypothesis that 1. The CNTF-induced VIP protein expression in human CEC is mediated through CNTF induction of VIP gene expression. 2. VIP is released from human CEC and is an autocrine factor for human CEC, and that there is an effect of aging on VIP/VIP receptor expression. 3, CNTF and VIP help to maintain the viability, the barrier function, & the integrity of CEC cell-cell junction and cell-matrix attachment in stored human corneas and in human cornea organ cultures.