Insulin-like growth factor II may play a local role in the regulation of ocular size

The ultimate size and shape of the eye has a profound influence on its refraction and function. However, the role of growth factors in normal ocular development is poorly understood. Insulin-like growth factors IGF-I and -II have major effects on cell growth and differentiation in tissue culture. Recently their importance for in vivo development has been studied; IGF-II is predominant prenatally, with a probable local role in the differentiation of some mesodermally derived tissues. Ocular development and size is partially dictated by the condensation of the outer collagenous scleral coat (the 'white') of the eye from orbital mesoderm. We investigated IGF-II expression and IGF-II receptor distribution during normal ocular development in the mouse fetus using in situ hybridization and immunohistochemistry. IGF-II mRNA was expressed by the loose mesenchymal orbital tissue as it differentiated to form the sclera, but not in the compact mature sclera or cornea, or in the ectodermally derived retina or skin. IGF-II gene expression was seen in the orbit at E14, reached a peak just before parturition and then declined to background levels after birth. Similarly, type 2 IGF receptors were shown with immunohistochemistry to be present on developing scleral cells and to be modulated in parallel with IGF-II mRNA expression. We suggest the IGF-II expression by differentiating cells that compact to form the collagenous ocular coat plays a local role in determining the ultimate shape and size of the developing eye.