The long-term goal of application EY04859 is the investigation of the genetic and microenvironmental factors that regulate the survival and differentiation of retinal neurons and photoreceptors. The studies are based on a multidisciplinary approach that involves: i) analysis of genetic influences by gene transfer into retinal cells in vivo and in vitro, ii) experimental manipulation of the cellular microenvironment in ovo and in culture, and iii) characterization of the phenotypic properties expressed by differentiating retinal cells using in situ hybridization, immunocytochemistry, autoradiography, single cell cDNA synthesis, RTPCR, real time PCR, Northern blots and image analysis. Aspects of the dynamics and regulation of photoreceptor cell differentiation that will be studied include: i) the developmental relationships between retinal progenitors that develop as rods or cones, ii) the coordinated expression of visual pigments and other photoreceptor specific-molecules during differentiation, iii) the development of outer segments, and iv) the effects on these phenomena of CNTF and the activin and BMP families of growth factors. The role of the homeobox genes Pax-6 and Chx-1O in the differentiation of retinal neurons and photoreceptors will also be investigated. The information derived from these studies is expected to further our understanding of the mechanisms of retinal development, and may also be relevant for some therapeutic approaches to retinal degenerations.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004859-21
Application #
6608119
Study Section
Special Emphasis Panel (ZRG1-SSS-Q (01))
Program Officer
Hunter, Chyren
Project Start
1983-01-01
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
21
Fiscal Year
2003
Total Cost
$510,149
Indirect Cost
Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Vergara, M Natalia; Gutierrez, Christian; Canto-Soler, M Valeria (2015) Efficient Gene Transfer in Chick Retinas for Primary Cell Culture Studies: An Ex-ovo Electroporation Approach. J Vis Exp :e52002
Springelkamp, Henriƫt; Mishra, Aniket; Hysi, Pirro G et al. (2015) Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology. Genet Epidemiol 39:207-16
Vergara, M Natalia; Gutierrez, Christian; O'Brien, David R et al. (2013) Ex vivo electroporation of retinal cells: a novel, high efficiency method for functional studies in primary retinal cultures. Exp Eye Res 109:40-50
Vergara, M Natalia; Canto-Soler, M Valeria (2012) Rediscovering the chick embryo as a model to study retinal development. Neural Dev 7:22
Vergara, M Natalia; de la Rosa, Enrique J; Canto-Soler, M Valeria (2012) Focus on molecules: proinsulin in the eye: precursor or pioneer? Exp Eye Res 101:109-10
Gutierrez, Christian; McNally, Minda; Canto-Soler, M Valeria (2011) Cytoskeleton proteins previously considered exclusive to ganglion cells are transiently expressed by all retinal neuronal precursors. BMC Dev Biol 11:46
McNally, Minda M; Wahlin, Karl J; Canto-Soler, M Valeria (2010) Endogenous expression of ASLV viral proteins in specific pathogen free chicken embryos: relevance for the developmental biology research field. BMC Dev Biol 10:106
Wahlin, Karl J; Hackler Jr, Laszlo; Adler, Ruben et al. (2010) Alternative splicing of neuroligin and its protein distribution in the outer plexiform layer of the chicken retina. J Comp Neurol 518:4938-62
Huang, Hu; Wahlin, Karl J; McNally, Minda et al. (2008) Developmental regulation of muscleblind-like (MBNL) gene expression in the chicken embryo retina. Dev Dyn 237:286-96
Wahlin, Karl J; Moreira, Ernesto F; Huang, Hu et al. (2008) Molecular dynamics of photoreceptor synapse formation in the developing chick retina. J Comp Neurol 506:822-37

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