Purchase this article with an account.
H. Jönsson, L. Fjord-Larsen, J. R. Jørgensen, T. van Veen, M. T. Perez; Retinal Expression of Receptors Specific for Neublastin/Artemin. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4486.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Neublastin/Artemin (NBN/ART), a member of the glial cell line derived neurotrophic factor (GDNF) family and a survival factor for sensory and sympathetic neurons, signals through the high-affinity GDNF family receptor alpha 3 (GFR-alpha3). The purpose of the present study was to examine the in vivo and in vitro expression of GFR-alpha3 in normal rodent retinas and in models of Retinitis Pigmentosa.
The distribution of GFR-alpha3 was analyzed by immunohistochemistry in retinas obtained from RCS (Royal College of Surgeon) rats, postnatal days 8 to 42 (P8-P42), and rd1 mice (P2-P28), as well as in retinas isolated from normal and rd1 mice (P5-7) cultured for 6-20 days. Specific markers of retinal cell types and structures (cellular retinal-binding protein (CRALBP), neurofilament (NF), neuron-specific nuclear protein (NeuN), and human neuronal antigen (Hu) were used to identify cells expressing GFR-alpha3.
In RCS rat retinas, expression of GFR-alpha3 was observed in retinal Müller glial cells, ganglion cells, and in retinal pigment epithelium (RPE) from P8 and onwards. Normal rat retinas showed the same pattern of developmental expression as dystrophic RCS rat retinas. In rd1 mouse retinas and congenic controls, GFR-alpha3 was expressed mainly in ganglion cells at all ages examined. In cultured mouse retinas (rd1 and control), GFR-alpha3 expression was decreased over the ganglion cell layer but was markedly increased in the inner plexiform layer.
Receptors specific for NBN/ART are expressed in several cell types in developing and adult retinas and are preserved in cultured retinas. The fact that GFR-alpha3 is expressed in retinal pigment epithelial and Müller glial cells and in ganglion cells indicates that NBN/ART has potential as a therapeutic molecule in the retina. It may be used alone or in combination with other neuroprotective factors to delay photoreceptor degeneration and/or ganglion cell loss in, for instance, glaucoma.
This PDF is available to Subscribers Only