The retinal pigment epithelial (RPE) cell has a major regulatory function in the eye, in a variety of ways influencing the maintenance of retinal integrity and function. In order to study this cell more effectively in vivo and in vitro, we have produced monoclonal antibodies directed against human RPE cells. Using immunoperoxidase assays (ABC), we have identified two mouse IgG monoclonal antibodies that react with the human RPE cell. The monoclonal antibodies are both specific for the RPE cell within the eye because they do not react with any other ocular structures. Moreover, these antibodies do not cross-react with human skin, kidney, or peripheral mononuclear cells. These antibodies recognize cell surface molecules that must be highly conserved, being found in man, monkey, rat, mouse, cow, chicken, and frog. These antibodies, which detect epitopes present solely on RPE cells, provide us with the unique opportunity to evaluate a variety of aspects of RPE cell development and function. Studies of RPE cell development indicate that the epitopes appear only after the cells have begun terminal differentiation. Moreover, these studies indicate that a very specific product of the RPE cell is synthesized as the photoreceptor outer segment starts to develop, suggesting that this product could be involved in an essential step of the outer segment development. Studies on RPE migration also demonstrate the value of these antibodies in evaluating epiretinal membrane formation. These are the first monoclonal antibodies directed solely at the human RPE cell. Further characterization and studies of these antibodies should prove useful in the identification of RPE cells in situ and in vitro. This immunoglobulin will allow us to probe the bioregulatory functions of the cells.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000233-05
Application #
3877056
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Honjo, Yasuyuki; Nagineni, Chandrasekharam N; Larsson, Jonas et al. (2007) Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice. Biochem Biophys Res Commun 352:418-22
Nagineni, Chandrasekharam N; Cherukuri, Karthik S; Kutty, Veena et al. (2007) Interferon-gamma differentially regulates TGF-beta1 and TGF-beta2 expression in human retinal pigment epithelial cells through JAK-STAT pathway. J Cell Physiol 210:192-200
Lee, M T; Hooper, L C; Kump, L et al. (2007) Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling. Clin Exp Immunol 147:71-80
Nagineni, Chandrasekharam N; Kutty, Veena; Detrick, Barbara et al. (2005) Expression of PDGF and their receptors in human retinal pigment epithelial cells and fibroblasts: regulation by TGF-beta. J Cell Physiol 203:35-43
Chen, Kevin G; Szakacs, Gergely; Annereau, Jean-Philippe et al. (2005) Principal expression of two mRNA isoforms (ABCB 5alpha and ABCB 5beta ) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes. Pigment Cell Res 18:102-12
Kumar, Matam Vijay; Nagineni, Chandrasekharam N; Chin, Marian S et al. (2004) Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells. J Neuroimmunol 153:7-15
Nagineni, Chandrasekharam N; Samuel, William; Nagineni, Sahrudaya et al. (2003) Transforming growth factor-beta induces expression of vascular endothelial growth factor in human retinal pigment epithelial cells: involvement of mitogen-activated protein kinases. J Cell Physiol 197:453-62
Momma, Yuko; Nagineni, Chandrasekharam N; Chin, Marian S et al. (2003) Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus. Invest Ophthalmol Vis Sci 44:2026-33
Samuel, William; Nagineni, Chandrasekharam N; Kutty, R Krishnan et al. (2002) Transforming growth factor-beta regulates stearoyl coenzyme A desaturase expression through a Smad signaling pathway. J Biol Chem 277:59-66
Nagineni, C N; Detrick, B; Hooks, J J (2002) Transforming growth factor-beta expression in human retinal pigment epithelial cells is enhanced by Toxoplasma gondii: a possible role in the immunopathogenesis of retinochoroiditis. Clin Exp Immunol 128:372-8

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