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HGF regulation of RPE proliferation in an IL-1beta/retinal hole-induced rabbit model of PVR.
Mol Vis. 2002 Dec 20; 8:494-501.MV

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-1beta(IL-1beta) 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-1beta, 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-1beta 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.

Authors+Show Affiliations

Department of Ophthalmology, Medical College of Georgia, Augusta, GA 30912, USA. giliou@mail.mcg.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12500176

Citation

Liou, Gregory I., et al. "HGF Regulation of RPE Proliferation in an IL-1beta/retinal Hole-induced Rabbit Model of PVR." Molecular Vision, vol. 8, 2002, pp. 494-501.
Liou GI, Pakalnis VA, Matragoon S, et al. HGF regulation of RPE proliferation in an IL-1beta/retinal hole-induced rabbit model of PVR. Mol Vis. 2002;8:494-501.
Liou, G. I., Pakalnis, V. A., Matragoon, S., Samuel, S., Behzadian, M. A., Baker, J., Khalil, I. E., Roon, P., Caldwell, R. B., Hunt, R. C., & Marcus, D. M. (2002). HGF regulation of RPE proliferation in an IL-1beta/retinal hole-induced rabbit model of PVR. Molecular Vision, 8, 494-501.
Liou GI, et al. HGF Regulation of RPE Proliferation in an IL-1beta/retinal Hole-induced Rabbit Model of PVR. Mol Vis. 2002 Dec 20;8:494-501. PubMed PMID: 12500176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HGF regulation of RPE proliferation in an IL-1beta/retinal hole-induced rabbit model of PVR. 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, Y1 - 2002/12/20/ PY - 2002/12/25/pubmed PY - 2002/12/31/medline PY - 2002/12/25/entrez SP - 494 EP - 501 JF - Molecular vision JO - Mol. Vis. VL - 8 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-1beta(IL-1beta) 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-1beta, 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-1beta 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. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/12500176/HGF_regulation_of_RPE_proliferation_in_an_IL_1beta/retinal_hole_induced_rabbit_model_of_PVR_ L2 - http://www.molvis.org/molvis/v8/a60/ DB - PRIME DP - Unbound Medicine ER -