STRUCTURE, DEVELOPMENT AND FUNCTION OF CYTOSKELETAL ELEMENTS IN NONNEURONAL CELLS OF THE HUMAN EYE

The cytoskeleton, of which the main components in the human eye are ac tin microfilaments, intermediate filaments and microtubules with their associated proteins, is essential for the normal growth, maturation, differentiation, integrity and function of its cells. These components interact with intra- and extracellular environment and each other, an d their profile frequently changes during development, according to ph ysiologic demands, and in various diseases. The ocular cytoskeleton is unique in many ways. A special pair of cytokeratins, CK 3 and 12, has apparently evolved only for the purposes of the corneal epithelium. H owever, other cytokeratins such as CK 4, 5, 14, and 19 are also import ant for the normal ocular surface epithelia, and other types may be ac quired in keratinizing diseases. The intraocular tissues, which have a relatively simple cytoskeleton consisting mainly of vimentin and simp le epithelial CK 8 and 18, differ in many details from extraocular one s. The iris and lens epithelium characteristically lack cytokeratins i n adults, and the intraocular muscles all have a cytoskeletal profile of their own. The dilator of the iris contains vimentin, desmin and cy tokeratins, bring an example of triple intermediate filament expressio n, but the ciliary muscle lacks cytokeratin rind the sphincter of the iris is devoid even of vimentin. Conversion from extraocular-type cyto skeletal profile occurs during fetal life. It seems that posttranslati onal modification of cytokeratins in the eye may also differ from that of extraocular tissues. So far, it has not been possible to reconcile the cytoskeletal profile of intraocular tissues with their specific f unctional demands, but many theories have been put forward. Systematic search for cytoskeletal elements has also revealed novel cell populat ions in the human eye. These include transitional cells of the cornea that may represent stem cells on migration, myofibroblasts of the scle ral spur and juxtacanalicular tissue that may modulate aqueous outflow , and subepithelial matrix cells of the ciliary body and myofibroblast s of the choroid that may both participate in accommodation. In contra st to the structure and development of the ocular cytoskeleton, change s that take place in ocular disease have not been analysed systematica lly. Nevertheless, potentially meaningful changes have already been ob served in corneal dystrophies (Meesmann's dystrophy, posterior polymor phous dystrophy and iridocorneal endothelial syndrome), degenerations (pterygium) and inflammatory diseases (Pseudomonas keratitis), in opac ification of the lens (anterior subcapsular and secondary cataract), i n diseases characterized by proliferation of the retinal pigment epith elium (macular degeneration and proliferative vitreoretinopathy), and in intraocular tumours (uveal melanoma). In particular, upregulation o f alpha-smooth muscle actin seems to be a relatively general response typical of spreading and migrating corneal stromal and lens epithelial cells, trabecular cells and retinal pigment epithelial cells. (C) 199 8 Elsevier Science Ltd. All rights reserved.