Involvement of cytoskelatal proteins and growth factor receptors during development of the human eye

Abstract

The spatial and temporal distribution of nestin, cytokeratins (CKs), vimentin, glial fibrillary acidic protein (GFAP), neurofilaments (NFs), beta-tubulin as well as fibroblast growth factor receptors (FGFRs) and platelet-derived growth factor receptor beta (PDGF-Rbeta) were investigated in the developing human eye in eight conceptuses of 5-9 postovulatory weeks using immunostaining. Nestin was found in the neuroglial precursors and the radial glial fibres of the optic nerve. In the pigmented retina, nestin was present only in the 5th week, while at later stages (6-9th week), co-expression of CKs and vimentin was seen. Nestin, CKs, vimentin, and GFAP were observed in the precursors to various cell types in the neural retina. Additionally, their expression was also apparent in the lens epithelium, showing its gradual fading following the lens fibre elongation. They appeared in the mesenchymal cells of the cornea, the choroid, the sclera, and the corpus vitreum, too. In the corneal epithelium, co-expression of nestin and CKs was detected. NFs and beta-tubulin were confined to the differentiating retinal neuroblasts. Growth factor receptors were seen in the retina, the lens epithelium while less intensely in the lens fibres, the corneal epithelium, and the mesenchymal cells. During the early eye development (5-9th week), IFs expressing normal pattern of distribution as well as acting in concert might contribute to the normal developmental processes occurring in certain parts of the human eye. Additionally, NFs and beta-tubulin seem to have an important role in the retinal ganglion cell differentiation, while FGFRs and PDGF-Rbeta may regulate the cell proliferation, differentiation, and survival in various parts of the developing eye.

Orbital Dysmorphology in Untreated Children with Crouzon and Apert Syndromes

“…1,18 FGFR-2 and associated receptors are known to be explicitly involved in eye development. [19][20][21][22] Sporadic cases of aniridia, anisocoria, blue sclera, cataract, corectopia, ectopia lentis, glaucoma, iris coloboma, megalocornea, microcornea have been described in Crouzon syndrome, whereas albinoid alterations of the fundus, among other conditions, have been associated with Apert syndrome. 4,15,23 Therefore, given the extensive connective tissue involvement seen with FGFR-2 mutations, and the receptor's role in extracellular matrix composition, including the role of FGFR-2 in the formation of corneal epithelium and periocular mesenchyme derived from cephalic neural crest cells, it is not surprising that globe development could be affected.…”

Functions of the intermediate filament cytoskeleton in the eye lens

“…These include BFSP1 and BFSP2 (11), vimentin (12,13), glial fibrillary acidic protein (GFAP) (14), simple epithelial keratins (14,15), nestin (16,17), and synemin (18). Of these, vimentin, BFSP1, and BFSP2 are the most highly expressed and also those that when mutated in humans can cause cataracts (6,19).…”

Intermediate filament protein nestin is expressed in developing meninges

“…The studies on human tissues and experimental animals revealed that nestin was highly expressed in neuroepithelial stem cells in CNS development and in gliomas (31,32). Recently, nestin was shown to be expressed in progenitor cells of developing human spinal ganglia (33) and optic nerve (34). Nestin was detected in neuronal precursor cells, developing skeletal and cardiac musle cells, mesonephric mesenchyme, pancreatic progenitor cells and vascular endothelium, among others (30).…”

“…Nestin was detected in neuronal precursor cells, developing skeletal and cardiac musle cells, mesonephric mesenchyme, pancreatic progenitor cells and vascular endothelium, among others (30). Nestin expression in those cells subsequently decreased at later developmental stages and fi nally disappeared in terminally differentiated and mature cells (33,34). Nestin expression was thought to be transient in these progenitor cells and differentiation in specialized cells types resulted in down-regulation of nestin and expression of other cells type-specifi c intermediate fi laments, like neurofi laments in neurons (35).…”