CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium

Rong Li, Rong Wen, Tina Banzon, Arvydas Maminishkis, Sheldon S. Miller

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Ciliary neurotrophic factor (CNTF) protects photoreceptors and regulates their phototransduction machinery, but little is known about CNTF's effects on retinal pigment epithelial (RPE) physiology. Therefore, we determined the expression and localization of CNTF receptors and the physiological consequence of their activation in primary cultures of human fetal RPE (hfRPE). Cultured hfRPE express CNTF, CT1, and OsM and their receptors, including CNTFRα, LIFRβ, gp130, and OsMRβ, all localized mainly at the apical membrane. Exogenous CNTF, CT1, or OsM induces STAT3 phosphorylation, and OsM also induces the phosphorylation of ERK1/2 (p44/42 MAP kinase). CNTF increases RPE survivability, but not rates of phagocytosis. CNTF increases secretion of NT3 to the apical bath and decreases that of VEGF, IL8, and TGFβ2. It also significantly increases fluid absorption (J V) across intact monolayers of hfRPE by activating CFTR chloride channels at the basolateral membrane. CNTF induces profound changes in RPE cell biology, biochemistry, and physiology, including the increase in cell survival, polarized secretion of cytokines/neurotrophic factors, and the increase in steady-state fluid absorption mediated by JAK/STAT3 signaling. In vivo, these changes, taken together, could serve to regulate the microenvironment around the distal retinal/RPE/Bruch's membrane complex and provide protection against neurodegenerative disease.

Original languageEnglish
Article numbere23148
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 2 2011

Fingerprint

Ciliary Neurotrophic Factor
Fluids and Secretions
neurotrophins
Retinal Pigments
Retinal Pigment Epithelium
Nerve Growth Factors
epithelium
pigments
secretion
Fluids
Phosphorylation
Physiology
Membranes
Ciliary Neurotrophic Factor Receptor
phosphorylation
Cytology
Bruch Membrane
Neurodegenerative diseases
Light Signal Transduction
physiology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium. / Li, Rong; Wen, Rong; Banzon, Tina; Maminishkis, Arvydas; Miller, Sheldon S.

In: PLoS One, Vol. 6, No. 9, e23148, 02.09.2011.

Research output: Contribution to journalArticle

Li, Rong ; Wen, Rong ; Banzon, Tina ; Maminishkis, Arvydas ; Miller, Sheldon S. / CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium. In: PLoS One. 2011 ; Vol. 6, No. 9.
@article{e3f305a9ca024b639ec37e338be4892c,
title = "CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium",
abstract = "Ciliary neurotrophic factor (CNTF) protects photoreceptors and regulates their phototransduction machinery, but little is known about CNTF's effects on retinal pigment epithelial (RPE) physiology. Therefore, we determined the expression and localization of CNTF receptors and the physiological consequence of their activation in primary cultures of human fetal RPE (hfRPE). Cultured hfRPE express CNTF, CT1, and OsM and their receptors, including CNTFRα, LIFRβ, gp130, and OsMRβ, all localized mainly at the apical membrane. Exogenous CNTF, CT1, or OsM induces STAT3 phosphorylation, and OsM also induces the phosphorylation of ERK1/2 (p44/42 MAP kinase). CNTF increases RPE survivability, but not rates of phagocytosis. CNTF increases secretion of NT3 to the apical bath and decreases that of VEGF, IL8, and TGFβ2. It also significantly increases fluid absorption (J V) across intact monolayers of hfRPE by activating CFTR chloride channels at the basolateral membrane. CNTF induces profound changes in RPE cell biology, biochemistry, and physiology, including the increase in cell survival, polarized secretion of cytokines/neurotrophic factors, and the increase in steady-state fluid absorption mediated by JAK/STAT3 signaling. In vivo, these changes, taken together, could serve to regulate the microenvironment around the distal retinal/RPE/Bruch's membrane complex and provide protection against neurodegenerative disease.",
author = "Rong Li and Rong Wen and Tina Banzon and Arvydas Maminishkis and Miller, {Sheldon S.}",
year = "2011",
month = "9",
day = "2",
doi = "10.1371/journal.pone.0023148",
language = "English",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium

AU - Li, Rong

AU - Wen, Rong

AU - Banzon, Tina

AU - Maminishkis, Arvydas

AU - Miller, Sheldon S.

PY - 2011/9/2

Y1 - 2011/9/2

N2 - Ciliary neurotrophic factor (CNTF) protects photoreceptors and regulates their phototransduction machinery, but little is known about CNTF's effects on retinal pigment epithelial (RPE) physiology. Therefore, we determined the expression and localization of CNTF receptors and the physiological consequence of their activation in primary cultures of human fetal RPE (hfRPE). Cultured hfRPE express CNTF, CT1, and OsM and their receptors, including CNTFRα, LIFRβ, gp130, and OsMRβ, all localized mainly at the apical membrane. Exogenous CNTF, CT1, or OsM induces STAT3 phosphorylation, and OsM also induces the phosphorylation of ERK1/2 (p44/42 MAP kinase). CNTF increases RPE survivability, but not rates of phagocytosis. CNTF increases secretion of NT3 to the apical bath and decreases that of VEGF, IL8, and TGFβ2. It also significantly increases fluid absorption (J V) across intact monolayers of hfRPE by activating CFTR chloride channels at the basolateral membrane. CNTF induces profound changes in RPE cell biology, biochemistry, and physiology, including the increase in cell survival, polarized secretion of cytokines/neurotrophic factors, and the increase in steady-state fluid absorption mediated by JAK/STAT3 signaling. In vivo, these changes, taken together, could serve to regulate the microenvironment around the distal retinal/RPE/Bruch's membrane complex and provide protection against neurodegenerative disease.

AB - Ciliary neurotrophic factor (CNTF) protects photoreceptors and regulates their phototransduction machinery, but little is known about CNTF's effects on retinal pigment epithelial (RPE) physiology. Therefore, we determined the expression and localization of CNTF receptors and the physiological consequence of their activation in primary cultures of human fetal RPE (hfRPE). Cultured hfRPE express CNTF, CT1, and OsM and their receptors, including CNTFRα, LIFRβ, gp130, and OsMRβ, all localized mainly at the apical membrane. Exogenous CNTF, CT1, or OsM induces STAT3 phosphorylation, and OsM also induces the phosphorylation of ERK1/2 (p44/42 MAP kinase). CNTF increases RPE survivability, but not rates of phagocytosis. CNTF increases secretion of NT3 to the apical bath and decreases that of VEGF, IL8, and TGFβ2. It also significantly increases fluid absorption (J V) across intact monolayers of hfRPE by activating CFTR chloride channels at the basolateral membrane. CNTF induces profound changes in RPE cell biology, biochemistry, and physiology, including the increase in cell survival, polarized secretion of cytokines/neurotrophic factors, and the increase in steady-state fluid absorption mediated by JAK/STAT3 signaling. In vivo, these changes, taken together, could serve to regulate the microenvironment around the distal retinal/RPE/Bruch's membrane complex and provide protection against neurodegenerative disease.

UR - http://www.scopus.com/inward/record.url?scp=80052394624&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052394624&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0023148

DO - 10.1371/journal.pone.0023148

M3 - Article

C2 - 21912637

AN - SCOPUS:80052394624

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e23148

ER -