Human secretory phospholipase A₂, group IB in normal eyes and in eye diseases

Abstract

ABSTRACT.Purpose: Secretory phospholipases A 2 (sPLA 2 ) are enzymes involved in lipid turnover. We recently identified sPLA 2 group IB (GIB) in the rat retina as well as in cerebral neurons and found upregulation to occur in response to light damage and seizures, respectively. The purpose of the present study was to identify human GIB (hGIB) in the normal human eye and investigate the pattern of expression in patients with eye diseases involving hGIB-rich cells. Methods: Human GIB mRNA was identified in the human retina by means of in situ hybridization and polymerase chain reaction. Antibodies against hGIB were obtained and immunohistochemical staining was performed on paraffinembedded sections of normal and pathological eyes. Donor eyes from patients with descemetization of the cornea, Fuchs' corneal endothelial dystrophy, agerelated macular degeneration, malignant choroidal melanoma, retinitis pigmentosa and glaucoma were evaluated. Results: Expression of hGIB was found in various cells of the eye. The most abundant expression was found in retinal pigment epithelium (RPE) cells, the inner photoreceptor segments, ganglion cells and the corneal endothelium. We explored diseases involving hGIB-rich cells and found downregulation of hGIB in proliferating RPE cells as well as in diseased corneal endothelial cells. Conclusions: Human GIB is highly expressed in cells with neurodermal origin. The pattern of expression of hGIB in diseases involving hGIB-rich cells demonstrated a downregulation of hGIB in migrating RPE cells and in diseased corneal endothelium.

The pathophysiology of Fuchs' endothelial dystrophy – A review of molecular and cellular insights

“…A reduction in phospholipid turnover observed by loss of labelling for GIB (secretory phospholipase A2 group 1B) indicating loss of endothelial function was noted in FECD endothelium (Kolko et al, 2007). Clusterin induced cell aggregation protects cells against injury by decreasing the amount of accessible cell membrane and maintaining cellecell contact; Clusterin labelling follows a distinct pattern in FECD with enhanced intracellular staining and dense staining around guttae and in the nuclei of endothelial cells; therefore it is suggested that clusterin induces endothelial cell aggregation in response to stress conditions (Jurkunas et al, 2008).…”

Purification and biochemical characterization of pancreatic phospholipase A2 from the common stingray Dasyatis pastinaca

“…sPLA2-IB is also highly expressed in the stomach and is present at lower levels in lung, spleen, liver, colon and eyes [7-9]. Receptors for this enzyme have been identified in various tissues, and group IB PLA2 is now reported to play a role in cell proliferation and hormone release via these receptors in non-digestive tissues [7,10,11].…”

Structural Insight into the Activation Mechanism of Human Pancreatic Prophospholipase A2

“…A recent report also pointed to the linkage between hG1B and ophthalmic diseases (6). Therefore, hG1B is considered to be a potential target for treatment of obesity, diabetes (4,5), or ophthalmic diseases (6).…”