HGF regulation of RPE proliferation in an IL-1β/retinal hole-induced rabbit model of PVR

Gregory I. Liou, Vytautas A. Pakalnis, Suraporn Matragoon, Sara Samuel, M. Ali Behzadian, Justin Baker, Ibrahim E. Khalil, Penny Roon, Ruth B Caldwell, Richard C. Hunt, Dennis M. Marcus

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Abstract

Purpose: To understand molecular events that lead to retinal pigment epithelial (RPE) cell proliferation and migration during the early phases of proliferative vitreoretinopathy (PVR) in a rabbit model. Methods: Retinal holes were created and interleukin-1β(IL-1β) was injected intravitreally. Eyes were examined by indirect ophthalmoscopy and eyecup pieces containing retinal holes were analyzed at different times after the surgery up to 4 weeks. RPE proliferation and migration were examined by immunohistochemistry. Tyrosine phosphorylation of extracellular signal regulated kinase (ERK) and hepatocyte growth factor receptor (HGFR or c-met) was determined by immunoprecipitation and western blot analysis. Tyrosine phosphorylation of c-met and morphological studies was performed on vitreous treated ARPE-19 cells. Expression of c-jun was determined by Northern blot analysis. Matrix metalloproteinase (MMP) content in vitreous was assessed by zymography. Results: Indirect ophthalmoscopy identified formation of epiretinal membrane and immunohistochemistry identified proliferative and migratory RPE and other cells in the posterior segment containing retinal holes at 4 weeks post-surgery. Tyrosine phosphorylation of ERK and c-met occurred in this segment within 30 min of surgery. ARPE-19 cells treated with vitreous from the 24 h post-surgical eyes, but not with control vitreous or IL-1β, showed morphological changes and tyrosine phosphorylation of c-met. Northern blot analysis in this segment identified upregulation of c-jun within 30 min of surgery and the expression peaked at 72 h. Zymographic analysis of vitreous identified MMP-9 in 12-72 h post-surgery. Conclusions: These data suggest that the presence of retinal holes and IL-1β may lead to activation of HGF, mitogen activated protein kinases (MAPK), c-jun and extracellular matrix remodeling, resulting in proliferative and migratory cells in the wounded retina.

Original languageEnglish (US)
Pages (from-to)494-501
Number of pages8
JournalMolecular Vision
Volume8
StatePublished - Dec 1 2002

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Proliferative Vitreoretinopathy
Retinal Perforations
Retinal Pigments
Interleukin-1
Tyrosine
Rabbits
Phosphorylation
Ophthalmoscopy
Extracellular Signal-Regulated MAP Kinases
Northern Blotting
Epithelial Cells
Immunohistochemistry
Proto-Oncogene Proteins c-met
Epiretinal Membrane
Matrix Metalloproteinase 9
Mitogen-Activated Protein Kinases
Matrix Metalloproteinases
Immunoprecipitation
Cell Movement
Extracellular Matrix

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Liou, G. I., Pakalnis, V. A., Matragoon, S., Samuel, S., Behzadian, M. A., Baker, J., ... Marcus, D. M. (2002). HGF regulation of RPE proliferation in an IL-1β/retinal hole-induced rabbit model of PVR. Molecular Vision, 8, 494-501.

HGF regulation of RPE proliferation in an IL-1β/retinal hole-induced rabbit model of PVR. / Liou, Gregory I.; Pakalnis, Vytautas A.; Matragoon, Suraporn; Samuel, Sara; Behzadian, M. Ali; Baker, Justin; Khalil, Ibrahim E.; Roon, Penny; Caldwell, Ruth B; Hunt, Richard C.; Marcus, Dennis M.

In: Molecular Vision, Vol. 8, 01.12.2002, p. 494-501.

Research output: Contribution to journalArticle

Liou, GI, Pakalnis, VA, Matragoon, S, Samuel, S, Behzadian, MA, Baker, J, Khalil, IE, Roon, P, Caldwell, RB, Hunt, RC & Marcus, DM 2002, 'HGF regulation of RPE proliferation in an IL-1β/retinal hole-induced rabbit model of PVR', Molecular Vision, vol. 8, pp. 494-501.
Liou GI, Pakalnis VA, Matragoon S, Samuel S, Behzadian MA, Baker J et al. HGF regulation of RPE proliferation in an IL-1β/retinal hole-induced rabbit model of PVR. Molecular Vision. 2002 Dec 1;8:494-501.
Liou, Gregory I. ; Pakalnis, Vytautas A. ; Matragoon, Suraporn ; Samuel, Sara ; Behzadian, M. Ali ; Baker, Justin ; Khalil, Ibrahim E. ; Roon, Penny ; Caldwell, Ruth B ; Hunt, Richard C. ; Marcus, Dennis M. / HGF regulation of RPE proliferation in an IL-1β/retinal hole-induced rabbit model of PVR. In: Molecular Vision. 2002 ; Vol. 8. pp. 494-501.
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abstract = "Purpose: To understand molecular events that lead to retinal pigment epithelial (RPE) cell proliferation and migration during the early phases of proliferative vitreoretinopathy (PVR) in a rabbit model. Methods: Retinal holes were created and interleukin-1β(IL-1β) was injected intravitreally. Eyes were examined by indirect ophthalmoscopy and eyecup pieces containing retinal holes were analyzed at different times after the surgery up to 4 weeks. RPE proliferation and migration were examined by immunohistochemistry. Tyrosine phosphorylation of extracellular signal regulated kinase (ERK) and hepatocyte growth factor receptor (HGFR or c-met) was determined by immunoprecipitation and western blot analysis. Tyrosine phosphorylation of c-met and morphological studies was performed on vitreous treated ARPE-19 cells. Expression of c-jun was determined by Northern blot analysis. Matrix metalloproteinase (MMP) content in vitreous was assessed by zymography. Results: Indirect ophthalmoscopy identified formation of epiretinal membrane and immunohistochemistry identified proliferative and migratory RPE and other cells in the posterior segment containing retinal holes at 4 weeks post-surgery. Tyrosine phosphorylation of ERK and c-met occurred in this segment within 30 min of surgery. ARPE-19 cells treated with vitreous from the 24 h post-surgical eyes, but not with control vitreous or IL-1β, showed morphological changes and tyrosine phosphorylation of c-met. Northern blot analysis in this segment identified upregulation of c-jun within 30 min of surgery and the expression peaked at 72 h. Zymographic analysis of vitreous identified MMP-9 in 12-72 h post-surgery. Conclusions: These data suggest that the presence of retinal holes and IL-1β may lead to activation of HGF, mitogen activated protein kinases (MAPK), c-jun and extracellular matrix remodeling, resulting in proliferative and migratory cells in the wounded retina.",
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AU - Liou, Gregory I.

AU - Pakalnis, Vytautas A.

AU - Matragoon, Suraporn

AU - Samuel, Sara

AU - Behzadian, M. Ali

AU - Baker, Justin

AU - Khalil, Ibrahim E.

AU - Roon, Penny

AU - Caldwell, Ruth B

AU - Hunt, Richard C.

AU - Marcus, Dennis M.

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N2 - Purpose: To understand molecular events that lead to retinal pigment epithelial (RPE) cell proliferation and migration during the early phases of proliferative vitreoretinopathy (PVR) in a rabbit model. Methods: Retinal holes were created and interleukin-1β(IL-1β) was injected intravitreally. Eyes were examined by indirect ophthalmoscopy and eyecup pieces containing retinal holes were analyzed at different times after the surgery up to 4 weeks. RPE proliferation and migration were examined by immunohistochemistry. Tyrosine phosphorylation of extracellular signal regulated kinase (ERK) and hepatocyte growth factor receptor (HGFR or c-met) was determined by immunoprecipitation and western blot analysis. Tyrosine phosphorylation of c-met and morphological studies was performed on vitreous treated ARPE-19 cells. Expression of c-jun was determined by Northern blot analysis. Matrix metalloproteinase (MMP) content in vitreous was assessed by zymography. Results: Indirect ophthalmoscopy identified formation of epiretinal membrane and immunohistochemistry identified proliferative and migratory RPE and other cells in the posterior segment containing retinal holes at 4 weeks post-surgery. Tyrosine phosphorylation of ERK and c-met occurred in this segment within 30 min of surgery. ARPE-19 cells treated with vitreous from the 24 h post-surgical eyes, but not with control vitreous or IL-1β, showed morphological changes and tyrosine phosphorylation of c-met. Northern blot analysis in this segment identified upregulation of c-jun within 30 min of surgery and the expression peaked at 72 h. Zymographic analysis of vitreous identified MMP-9 in 12-72 h post-surgery. Conclusions: These data suggest that the presence of retinal holes and IL-1β may lead to activation of HGF, mitogen activated protein kinases (MAPK), c-jun and extracellular matrix remodeling, resulting in proliferative and migratory cells in the wounded retina.

AB - Purpose: To understand molecular events that lead to retinal pigment epithelial (RPE) cell proliferation and migration during the early phases of proliferative vitreoretinopathy (PVR) in a rabbit model. Methods: Retinal holes were created and interleukin-1β(IL-1β) was injected intravitreally. Eyes were examined by indirect ophthalmoscopy and eyecup pieces containing retinal holes were analyzed at different times after the surgery up to 4 weeks. RPE proliferation and migration were examined by immunohistochemistry. Tyrosine phosphorylation of extracellular signal regulated kinase (ERK) and hepatocyte growth factor receptor (HGFR or c-met) was determined by immunoprecipitation and western blot analysis. Tyrosine phosphorylation of c-met and morphological studies was performed on vitreous treated ARPE-19 cells. Expression of c-jun was determined by Northern blot analysis. Matrix metalloproteinase (MMP) content in vitreous was assessed by zymography. Results: Indirect ophthalmoscopy identified formation of epiretinal membrane and immunohistochemistry identified proliferative and migratory RPE and other cells in the posterior segment containing retinal holes at 4 weeks post-surgery. Tyrosine phosphorylation of ERK and c-met occurred in this segment within 30 min of surgery. ARPE-19 cells treated with vitreous from the 24 h post-surgical eyes, but not with control vitreous or IL-1β, showed morphological changes and tyrosine phosphorylation of c-met. Northern blot analysis in this segment identified upregulation of c-jun within 30 min of surgery and the expression peaked at 72 h. Zymographic analysis of vitreous identified MMP-9 in 12-72 h post-surgery. Conclusions: These data suggest that the presence of retinal holes and IL-1β may lead to activation of HGF, mitogen activated protein kinases (MAPK), c-jun and extracellular matrix remodeling, resulting in proliferative and migratory cells in the wounded retina.

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