The RPE cell plays a basic role in maintaining the structural and physiological integrity of the neural retina. Alterations in its structural and functional actions can result in loss of photoreceptors and vision. We have studied the RPE cell extensively as an important immunoregulatory cell within the posterior pole of the eye. Our research activities on RPE cells can be subdivided into three categories: normal cell function studies, cytokine interactions and infectious processes.Cytokines, such as interferon (IFN)-gamma and IL-2, are a group of specialized hormone-like proteins which exert profound influences on cellular development and on a variety of cellular functions. This project has concentrated on studying the ways in which cytokines interact with cells of the immune system and with cells in the ocular microenvironment. These studies indicate that cytokine- mediated activation of RPE cells may be a basic component of ocular immunity and an important aspect of RPE cell transplantation. During the past year, we have studied the interactions of infectious agents with HRPE cells and the subsequent activation of cytokine gene expression. We found that cytomegalovirus (CMV) infection of HRPE cells results in the enhanced secretion of the cytokine, IL-6 and the growth factor, GM-CSF. Northern blot analysis showed enhanced mRNA levels suggesting activation at the transcriptional level. CMV induced cytokine gene expression and protein production were down-regulated by CMV anti-sense oligonucleotide treatment. IL-6 is a proinflammatory cytokine which can be detected within the vitreous during human diseases and can induce uveitis following IL-6 injection. The ability of CMV to trigger cytokine and growth factor gene expression and production in RPE cells may identify one of the ways that viruses promote ocular inflammation. Moreover, this mechanism of cytokine production by HRPE cells may be a site of future therapeutic strategies for ocular inflammation - retinal pigment epithelium, RPE, cytokines, cytomegalovirus

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000233-14
Application #
6290113
Study Section
Special Emphasis Panel (LI)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1999
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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