This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To determine whether compounds that generate nitric oxide (NO) can relax carbachol contracted or resting ciliary muscle (CM) in vitro. This is an indicator of whether this class of compounds may be useful in enhancing uveoscleral outflow as an approach for lowering intraocular pressure in glaucoma. To determine whether the monkey anterior segment in organ culture responds to compounds known to increase trabecular outflow; this system can then be used to investigate the effects of gene therapy and other molecules on trabecular outflow which may also be utilized for glaucoma therapy. Nitric oxide (NO) donors such as SNP and ISDN were most effective in relaxing precontracted CM in vitro. The non-selective NO synthase inhibitor L-NAME induced further contraction, possibly suggesting some endogenous production of NO in the longitudinal CM. Signaling pathways utilized to induce the relaxation are being determined. NO compounds have potential value in therapeutic areas where relaxation (NO donors) or contraction (possibly NO synthase inhibitors) of the CM is desirable, such as the treatment of glaucoma. The monkey organ-cultured anterior segment system was established. H-7, a compound shown to increase outflow facility in monkey eyes in vivo, was also effective in increasing outflow facility in vitro, thus validating the technique. Viral vectors containing two different genes that alter the actin cytoskeleton were also found to be effective in increasing outflow facility in this system by targeting the trabecular meshwork outflow pathway. This gene therapy approach for the anterior segment has the potential to be utilized for glaucoma therapy to decrease intraocular pressure. This research used WNPRC Research Services.
Showing the most recent 10 out of 528 publications