Abstract
Purpose: :
Our previous results showed that neurotrophin-3 (NT-3) regulates the maturation of retinal ganglion cells, but less is known whether and how NT-3 regulates the development of other types of retinal neurons. In this study, we investigated the roles of NT-3 in the development of dopaminergic amacrine cells in the mouse retina.
Methods: :
We used a transgenic mouse model in which NT-3 continuously overexpress from lens fibers under the control of the alphaA-crystallin promoter. Dopaminergic amacrine cells were stained with tyrosine hydroxylase (TH) antibody to examine their distribution and morphology during postnatal development. The density and the tiling pattern of TH cells were analyzed in whole-mounted retinas of NT-3 overexpression mice (NT-3-OE) and their littermate wildtype controls. To examine overexpression of NT-3 affects cell apoptosis during the first postnatal week, TUNEL staining was performed. Furthermore, cell mitosis was examined using antibody against phospho-histone H3, a maker of M phase cells in mitosis, and BrdU staining, which detects S phase of mitosis.
Results: :
Compared to age-matched wildtype controls, higher density of TH-positive amacrine cells were found in NT-3-OE mice. Visual experience did not affect the developmental increase of TH cells in WT mice. More TH cells were observed in NT-3 OE mice by the time of eye opening, and they exhibit more mature morphology. We further examined the mechanism underlying this precocious maturation and found that NT-3 did not affect cell apoptosis but mitosis.
Conclusions: :
Overexpression of NT-3 promotes retinal neurons to differentiate into dopaminergic neurons and accelerates its maturational process during postnatal development.
Keywords: retinal development • growth factors/growth factor receptors • amacrine cells