The ciliary body is a small secretory tissue in the anterior portion of the eye. It produces and aqeuos fluid that bathes and nourishes the lens and cornea and is the only circulation system for these two tissues. The intraocular pressure resulting from continual fluid production is essential for eye growth. Micro-ophthalmia, a severe reduction in eye growth during development, is thought to be caused by decreased fluid production. When elevated, intraocular pressure is the most common risk factor for glaucoma, a leading cause of blindness worldwide and the major cause nation-wide. The ciliary body epithelium is also a source of stem cells for the retina. In spite of its essential role in eye organogenesis and homeostasis, the mechanism of cilairy body formation during development is not well understood. The ciliary body is derived from the neuroepithelium of the optic cup. During development, interactions with the lens or with the neural crest-derived mesenchyme have been suggested to specify a portion of the optic cup as the ciliary body. However, preliminary findings presented here show that a) the ciliary body epithelium can be specified independently of the lens, and b) the ciliary body epithelium can be ectopically specified at the interface between neural retina and pigmented epithelium tissue in the posterior of the eye, away from the lens. The following hypotheses will be tested: 1) The ciliary body is not specified by the physical lens; 2) Combinatorial signals, as found in the interface between neural retina and pigmented epithelium, specify the ciliary body; and 3) after specification, the lens is important in maintaining ciliary body fate. The first hypothesis will be tested by examining ciliary body development in optic cups with the lenses removed and on the borders between ectopically induced neural retina tissue and pigmented epithelial tissue (Aims 1). Next, as the borders between ectopic neural retina and pigmented epithelium are areas of overlapping FGF and BMP-like signals, the effect of combined FGF/Activin and FGF/BMP signaling on ciliary body specification and differentiation will be analyzed in vitro and in vivo (Aims 2). Finally, the role of the lens in maintaining and/or inducing ciliary epithelium cell fate will be assessed in vivo and in - in vitro explant cultures (Aims 3). This information may help to develop treatments for micro-ophthalmia and glaucoma.
