These retinal images are from an 84 year old white male who presented to the Moran Eye Center in 2008. He was diagnosed and followed for dry age-related macular degeneration (AMD) with serial autofluorescent photographs showing progression of geographic atrophy of the RPE from 2008 to 2014.
These images were prepared by James Gilman of the Moran Eye Center.
This abstract was presented today at the 2014 Association for Research in Vision and Opthalmology (ARVO) meetings in Orlando, Florida by Haibo Wang, Yanchao Jiang and M. Elizabeth Hartnett.
Thy-1 regulates VEGF-induced choroidal endothelial cell migration
Dept of Ophthalmology, John A. Moran Eye Center, The University of Utah-Salt Lake City.
Purpose: Choroidal endothelial cell (CEC) activation and migration precede the development of choroidal neovascularization in neovascular AMD. Thy-1 is a cell surface protein expressed on different cells, including neurons and endothelial cells. As a glycosylphosphatidylinositol (GPI)-anchored glycoprotein, Thy-1 is located in lipid raft microdomains within the cell membrane, which brings Thy-1 into proximity of signaling molecules including cytoplasmic tyrosine kinases that can modulate adhesive and migratory events. In the retina, Thy-1 is well known as a retinal ganglion cell marker. Given the possibility that Thy-1 might be expressed in CECs, we addressed the hypothesis that upregulated Thy-1 in CECs by age-related stresses contributes to CEC migration.
Methods: Western blots of Thy-1 were determined in retinal pigment epithelial cells (RPE) and CECs. By real time quantitative PCR, Thy-1 mRNA was measured in CECs treated with vascular endothelial growth factor (VEGF) (20 ng/ml), CCL11 (100 ng/ml) or PBS for 24 hours, or in RPE/choroids from young (<40 yrs) and old (>60 yrs) donor eyes. Immunohistochemistry of Thy-1 was performed in posterior globe sections of human retina/RPE/choroids in the maculas of young and old donor eyes with or without AMD. Colabeling with VE-cadherin was used to identify CECs. CECs transfected with Thy-1 siRNA or control siRNA were stimulated with VEGF, and CEC migration and phosphorylation of VEGF receptor 2 (VEGFR2) were measured. Statistics were performed using ANOVA.
Results: Thy-1was highly expressed in CECs but not in RPE. Thy-1 staining was not only detected in the retinal ganglion cell layer, but also in the choroid, and colocalized to a greater extent with VE-cadherin labeled CECs in sections from donors with AMD compared to age-matched controls without AMD. Thy-1 mRNA was significantly increased in CECs treated with VEGF or CCL11 (p<0.05 vs. PBS) and greater in RPE/choroids from aged donor eyes (p<0.001 vs. young). Knockdown of Thy-1 in CECs by siRNA transfection significantly inhibited VEGF-induced CEC migration (p<0.001) and VEGFR2 activation.
Conclusions: Thy-1is expressed in CECs and its expression is upregulated by stresses associated with neovascular AMD, including elderly age and increased VEGF. Upregulated Thy-1 in CECs contributes to VEGF-induced VEGFR2 activation and CEC migration. Future studies into the potential role of Thy-1 in neovascular AMD are being considered.
The Moran Eye Center‘s Dr. Gregory Hageman delivered a Congressional Briefing on September 20th along with the Alliance for Eye and Vision Research (AEVR) and partners AMD Alliance International, Alliance for Aging Research, Association for Research in Vision and Ophthalmology (ARVO), European Vision Institute and Lighthouse International. Dr. Hageman spoke as part of a Congressional briefing as part of International Age-related Macular Degeneration (AMD) Awareness Week 2012.
Dr. Gregory Hageman, Executive Director of the Center for Translational Medicine (CTM) at the John A. Moran Eye Center at the University of Utah related in his address that AMD consists of multiple biological diseases. Dr. Hageman continued by expressing that a convergence of clinical, biological and genetic data has led to a stronger understanding of the disease and new hope for the development of diagnostics and therapeutic interventions currently underway.
More details of the briefing are available on the NAEVR website here.
This poster was presented today at the Association for Research in Vision and Opthalmology (ARVO) meetings in Ft. Lauderdale, Florida by W. Drew Ferrell, Lloyd Williams, Carl B. Watt, James R. Anderson, Robert E. Marc and Bryan William Jones. Full size (almost) poster can be seen here.
On Tuesday, March 20, 2012 from 4:00 – 5:00pm, Bärbel Rohrer, Ph.D. will be delivering a talk on “Sublytic Compliment Activation in Age-Related Macular Degeneration” at the Eccles Institute of Human Genetics auditorium on the University of Utah campus.
Refreshments will be provided after the seminar for socialization.
Faculty Host: Bryan William Jones, Ph.D.
Questions? Leave a comment/question here or contact Tracy Marble at 801 581-4820.
Continue reading “Seminar: Bärbel Rohrer, Ph.D. “Sublytic Complement Activation in Age-Related Macular Degeneration””
Efforts to explore chromosome 10q26, a major candidate region associated with age-related macular degeneration (AMD) have proven difficult and controversial. This particular region of interest is two neighboring genes, ARMS2 and HTRA1. However, efforts in trying to explore the functional involvement of either HTRA1 or ARMS2 in AMD have proven to be difficult and have often yielded conflicting results.
Continue reading “Notable Paper: Increased Expression of Multifunctional Serine Protease, HTRA1, in Retinal Pigment Epithelium Induces Polypoidal Choroidal Vasculopathy”