Growth Effect of VIP on Human Trabecular Meshwork

Glaucoma is a blinding disease affecting mainly the population over the age of 40. In spite of intensive studies, the causes of the disease is not known. The trabecular meshwork (TM), a tissue believed to be involved “in the regulation of the intraocular pressure has been the target of many studies. A decrease in cell numbers in the TM is found to correlate with the aging process and the glaucomatous condition of the eyes. Laser trabeculoplasty consisting of the application of small focal laser bums to the TM is commonly used to treat the glaucoma after failure of the anti-glaucoma drug therapy. It is effective in lowering the intraocular pressure, however its long-term effect is in question. The treated-eyes often require subsequent surgery. The mechanism of trabeculoplasty in lowering the intraocular pressure in treated eyes is unknown. Using explant organ cultures of the human eyes from the eye bank, investigators have demonstrated that, after the laser treatment, there is an immediate decrease in the cell numbers followed by division of the TM cells and repopulation of the TM. It has been postulated that these newly grown TM cells are responsible for the restored TM function. Since studies of the explant organ cultures have demonstrated that the number of cells that divide after laser treatment is very small, we may be able to increase the rate of cell division of these dividing cells to better repair the TM. Specifically, we ask whether applying a bioactive compound capable of increasing the rate of cell division to the TM immediately after the trabeculoplasty treatment will have a beneficial effect on the cellular repopulation of the TM. Vasoactive intestinal peptide (VIP), a 28-amino-acid neuropeptide, is a regulator of cell growth and differentiation in a variety of cells, including some cells of the eye. Recent studies by Dr. Brenneman (consultant of the proposed studies) and colleagues have shown that VIP exerts a dramatic growth effect on whole embryos in culture. VIP has also been shown to promote the survival of neuronal cells. Very recently, VIP has been found in the liquid which continuously bathes the TM in the eye. Furthermore, VIP has been demonstrated within the TM of the human eyes. Previously, we have demonstrated that the TM cells are responsive to VIP stimulation and divide at a faster rate in the presence of VIP in tissue culture. It is therefore likely that VIP in the liquid bathing the TM can modulate the growth the TM. In order to demonstrate that VIP-stimulated division of TM cells is of possible physiological significance, we will study the effects of VIP on the division of TM cells in organ cultures of human TM from eye bank eyes. Our preliminary studies using bisections of a corneoscleral rim from a 73-year old donor eye demonstrated that treatment with VIP for 48 hours resulted in a highly significant increase in the number of dividing cells. Although the mechanism of laser trabeculoplasty action is unknown, it appears to trigger cell mitosis of a specific population of the TM cells. We will examine the possibility that VIP treatment of the TM in explants organ cultures immediately after laser trabeculoplasty will stimulate the rate of cell division of these dividing cells. Recent pharmacological studies of VIP have generated a VIP analog that is suitable for topical (transdermal) application and found effective in the treatment of impotence of the rat. This VIP analog may prove to be useful for topical application to the eye. Thus, the proposed studies designed to establish a role for VIP as a promoter of cell division of TM cells may lead to the refinement of the trabeluloplasty, a noninvasive procedure for treating glaucoma.