Aqueous Humor sCD44 Concentration and Visual Field Loss in Primary Open-angle Glaucoma

Nolan, Michael; Giovingo, Michael; Miller, Adam; Wertz, Robert D.; Ritch, Robert; Liebmann, Jeffrey M.; Allingham, R. Rand; Herndon, Leon W.; Wax, Martin B.; Smolyak, Regina; Fareed, Hasan; Barnett, Edward M.; Samples, John R.; Knepper, Paul A.

doi:10.1097/ijg.0b013e318050ab4b

Cited by 32 publications

(25 citation statements)

References 63 publications

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“…The table in the genetics chapter (Chap. 9, 10 have both pointed this out. A cellular stress model of glaucoma is important in a biological sense because it can lead to a different perspective on treatment.…”

Section: Other Glaucoma Genesmentioning

confidence: 90%

What Really Causes Glaucoma?

Samples

2010

The Glaucoma Book

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Section: Other Glaucoma Genesmentioning

confidence: 90%

What Really Causes Glaucoma?

Samples

2010

The Glaucoma Book

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“…CD44 plays major roles in multiple physiological processes, including innate 8,9 and adaptive immunity, 10,11 phagocytosis, 12,13 and cell survival pathways. [14][15][16] sCD44 is elevated in the aqueous humor of POAG versus non-POAG patients, 3,5,17,18 and its concentration correlates with the extent of visual field loss in POAG. 5 A hypo-phosphorylated form of sCD44 in POAG aqueous humor further distinguishes POAG and normal pressure glaucoma from normal eyes and other types of glaucoma.…”

Section: Methodsmentioning

confidence: 99%

“…[14][15][16] sCD44 is elevated in the aqueous humor of POAG versus non-POAG patients, 3,5,17,18 and its concentration correlates with the extent of visual field loss in POAG. 5 A hypo-phosphorylated form of sCD44 in POAG aqueous humor further distinguishes POAG and normal pressure glaucoma from normal eyes and other types of glaucoma. 19 Moreover, sCD44, particularly the hypo-phosphorylated form of sCD44, is a potent and specific cytotoxin to trabecular meshwork (TM) and retinal ganglion cells.…”

Section: Methodsmentioning

confidence: 99%

“…1 Previous studies from our laboratory have identified soluble CD44 (sCD44) as a likely protein marker and causative factor of POAG, especially in African American individuals. [2][3][4][5] CD44 is an 80-to 250-kD transmembrane protein; its ectodomain is released as 32-kD sCD44 and remains biologically active. 6,7 The liberated sCD44 binds ligands acting as a decoy receptor and also binds homotypically.…”

Section: Methodsmentioning

confidence: 99%

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sCD44 Internalization in Human Trabecular Meshwork Cells

Nolan

Koga

Walker

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To determine whether soluble CD44 (sCD44), a likely biomarker of primary open-angle glaucoma (POAG), is internalized in cultured human trabecular meshwork (TM) cells and trafficked to mitochondria. METHODS.In vitro, 32-kD sCD44 was isolated from human sera, biotinylated, and dephosphorylated. TM cells were incubated for 1 hour at 48C with biotinylated albumin (b-albumin), biotinlabeled sCD44 (b-sCD44), or hypophosphorylated biotinlabeled sCD44 (-p b-sCD44) in the presence or absence of unlabeled sCD44, hyaluronic acid (HA), and a selected 10-mer HA binding peptide. The slides were warmed for 1 or 2 hours at 378C, and 125 nM MitoTracker Red was added for the last 20 minutes of the incubation. The cells were washed, fixed, incubated with anti-biotin antibody and FITC-labeled goat antimouse antibody, and examined under a confocal microscope.RESULTS. TM cell membranes were positive for b-sCD44 after 48C incubation. When the temperature was raised to 378C, bsCD44 or -p b-sCD44 appeared in the cytoplasm. The internalization of b-sCD44 was blocked by excess unlabeled sCD44, HA, and a 10-mer HA-binding peptide. Double label experiments with b-sCD44 or -p b-sCD44 and MitoTracker Red indicated partial overlap. The percent co-localization of MitoTracker Red at 2 hours and FITC -p b-sCD44 was 17.4% (P < 0.001) and for FITC b-sCD44 was 11.7% (P < 0.001) compared with b-albumin. The influence of putative CD44 phosphorylation sites on mitochondrial trafficking was determined by TargetP 1.1.CONCLUSIONS. sCD44 is internalized by TM cells and trafficked in part to mitochondria, which may be a factor in the toxicity of sCD44 in the POAG disease process. (Invest Ophthalmol Vis Sci. 2013;54:592-601)

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“…This has motivated investigators to collect and analyze AH, e.g. (Nolan et al, 2007). Collection is accomplished by insertion of a needle into the anterior chamber of the eye and aspiration of a small volume of AH from eyes of patients undergoing surgery for glaucoma or for cataract (as a control group).…”

Section: Introductionmentioning

confidence: 99%