Differentiation and migration of astrocyte precursor cells (APCs) and astrocytes in human fetal retina: relevance to optic nerve coloboma

The presence of astrocyte precursor cells (APCs) and time course and topogr aphy of astrocyte differentiation during development were investigated by t riple-label immunohistochemistry with intact fetal and adult human retinas. Throughout retinal development and adulthood, expression of Pax2 was restr icted to cells of the astrocytic lineage. Three distinct stages of astrocyt ic differentiation were identified during development: i) Pax2(+)/vimentin( +)/GFAP(-) APCs; ii) Pax2(+)/vimentin(+)/GFAP(+) immature perinatal astrocy tes; and iii) Pax2(+)/vimentin(-)/GFAP(+) mature perinatal astrocytes. In a dult, cells with the antigenic phenotype of mature perinatal astrocytes wer e restricted to a region surrounding the optic nerve head (ONH), whereas ce lls at a fourth stage of differentiation, adult astrocytes (Pax2(-)/vimenti n(-)/GFAP(+)), were apparent throughout the vascularized retina. APC appear ance was centered around the ONH and preceded the appearance of perinatal a strocytes. A cluster of Pax2(+) somas was also present in a small region su rrounding the ONH at the ventricular surface of the developing retina, whic h suggests the existence of two distinct sites of astrocytic differentiatio n. The coincidence in the location of APCs and perinatal astrocytes at the ventricular zone with that of optic nerve colobomas, together with the asso ciation of Pax2 gene mutations with this condition, suggests that coloboma formation may result from impaired astrocyte differentiation during develop ment.