TCCR/WSX-1 is a novel angiogenic factor in age-related macular degeneration.
OBJECTIVE
Age-related macular degeneration (AMD) is the major cause of blindness among persons aged 60 years and older. The current approved therapies for AMD are exclusively limited to inhibiting vascular endothelial growth factor. However, substantial improvement in vision occurs in only one-third of patients treated with vascular endothelial growth factor antagonists, and one-sixth of treated patients still progress to legal blindness. Therefore, more specific targets are needed to treat AMD. Our goal was to find secretory proteins that change in number in the aqueous humor and that cause exudative AMD disease.


METHODS
The number of molecules changed in the aqueous humor of patients with AMD compared to the control group was determined using antibody array analysis. The levels of angiopoietin-2 and insulin-like growth factor binding protein-related protein 7 were measured using enzyme-linked immunosorbent assay. The levels of T-cell cytokine receptor (TCCR/WSX-1) were determined using western blot. Potential TCCR/WSX-1-mediated effects on tube formation as well as phosphorylation of extracellular signal-regulated kinase in human umbilical vein endothelial cells were determined.


RESULTS
We found that the numbers of several molecules were changed in the aqueous humor of patients with AMD compared to the control group. Among them, angiopoietin-2 was reduced by 20% and TCCR/WSX-1 was increased twofold. Moreover, exogenous TCCR protein induced tube formation and phosphorylation of extracellular signal-regulated kinase in human umbilical vein endothelial cells.


CONCLUSIONS
Our study suggests that TCCR/WSX-1 is closely associated with angiogenesis and could serve as a novel therapeutic target in patients with AMD.
Functional Genomics Branch, Division of Convergence Technology, National Cancer Center, Gyeonggi-do, Republic of Korea.
Ho Jin
HJ
Sung
Jung Il
JI
Han
Ji Won
JW
Lee
Ki Bang
KB
Uhm
Kyun
K
Heo
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D001082:Aqueous Humor / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005123:Eye / Q000098:blood supply*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D040081:Protein Array Analysis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; D015415:Biomarkers; D005136:Eye Proteins; C112441:IL27RA protein, human; D018123:Receptors, Interleukin; D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases