The retinal pigment epithelial (RPE) cell plays a basic role in maintaining the structural and physiological integrity of the neural retina. We have isolated and propagated RPE cells in vitro and have developed monoclonal antibodies directed against human RPE cells. We are using these techniques and reagents to evaluate molecular, biochemical, and biological properties of the RPE cells. Because the monoclonal antibodies detect epitopes present solely on RPE cells, they provide us with the unique opportunity to evaluate a variety of aspects of RPE cell development and function. Studies on RPE cell development indicate that the epitopes appear only after the cells have begun terminal differentiation. Moreover, studies on RPE migration also demonstrate the value of these antibodies in evaluating epiretinal membrane formation. The RPE epitope is a 67 kD protein that is closely associated with the microsomal membrane. We have isolated a cDNA clone that codes for a protein which matches no other sequence in the data bases. Studies are also in progress to propagate and transplant RPE cells in various animals. We have propagated human RPE cells in vitro and evaluated their ability to respond to cytokine activation. RPE cells respond to retinal aberrations by dying, proliferating, migrating, losing phagocytic function, expressing major histocompatibility complex (MHC) class II antigens, and presenting antigens to T lymphocytes. The techniques and reagents obtained in these studies allow us to evaluate the mechanisms involved in aberrant RPE cell responses. Moreover, they provide the framework to evaluate RPE cell transplantation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000233-07
Application #
3841224
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1992
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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