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Am J Physiol Cell Physiol (October 7, 2009). doi:10.1152/ajpcell.00255.2009
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Research Article

IFN{gamma} Regulates Retinal Pigment Epithelial Fluid Transport

Rong Li,1 Arvydas Maminishkis,1 Tina Banzon,1 Qin Wan,1 Stephen Jalickee,1 Shan Chen,1 and Sheldon S Miller1,*

1National Institutes of Health

Submitted 15 June 2009 ; revised 14 September 2009 ; accepted in final form 25 September 2009

The present experiments show that IFN{gamma} receptors are mainly localized to the basolateral membrane of human retinal pigment epithelium (RPE). Activation of these receptors in primary cultures of human fetal RPE inhibited cell proliferation and migration, decreased RPE mitochondrial membrane potential, altered transepithelial potential and resistance, and significantly increased transepithelial fluid absorption (JV). These effects are mediated through JAK/STAT and P38 MAPK signaling pathways. Second messenger signaling through cAMP/PKA and IRF-1 dependent production of nitric oxide/cGMP stimulated the cystic fibrosis transmembrane conductance regulator (CFTR) at the basolateral membrane and increased transepithelial fluid absorption. In vivo experiments using a rat model of retinal reattachment showed that IFN{gamma} applied to the anterior surface of the eye can remove extra fluid deposited in the extracellular or subretinal space (SRS) between the retinal photoreceptors and RPE. This removal was blocked by a combination of PKA and JAK/STAT pathway inhibitors injected into the SRS. These results demonstrate a protective role for IFN{gamma} in regulating retinal hydration across the outer-blood-retinal barrier in inflammatory disease processes and provide the basis for possible therapeutic interventions.

CFTR; cGMP; NO; cytokine


* National Institutes of Health millers{at}nei.nih.gov






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