Growth factors induce neurogenesis in the ciliary body

The ciliary body of the eye is a nonneural tissue that is derived from the anterior rim of the optic cup, an extension of the neural tube. This tissue normally does not contain neurons and functions to produce components of the aqueous humor. We found that intraocular injections of insulin, EGF, or FGF2 stimulate NPE cells to proliferate and differentiate into neurons. These growth factors had region-specific effects along the radial axis of the ciliary body, with insulin and EGF stimulating proliferation of NPE cells close to the retina, while FGF2 stimulated the proliferation of NPE cells further toward the lens. Similar region-specific effects were observed for accumulations of neurons in the NPE in response to injections of different growth factors. The neurons derived from NPE cells express neurofilament, beta3 tubulin, RA4, calretinin, Islet1, or Hu, and a few produced long axonal projections, several millimeters in length that extend across the ciliary body. Our results suggest that the ciliary body has the capacity to generate retinal neurons, but normally neurogenesis is actively inhibited.