Abstract
Purpose: :
Pterygium is associated with ultraviolet-light exposure, which may have detrimental effects either directly (UV phototoxic effect) or indirectly, through radical oxygen species (ROS) formation. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the human population, affecting over 200 million people worldwide and about 10% of Sardinian population. G6PD is the key cytosolic enzyme in the pentose phosphate pathway,that has a major role in generating pentose and NADPH, indispensable for maintenance of cellular redox homeostasis.In order to understand the possible implication of G6PD deficiency on pterygium development, we evaluated the prevalence of G6PD deficiency in a population with pterygium, the growth rate, the expression of G6PD gene, and the cholesterol metabolism in pterygium fibroblasts (PFs) isolated from G6PD (+) and (-) individuals.
Methods: :
A retrospective, observational study was conducted on 116 patients (92 males/ 24 females; mean age 56.7 ± 14.4 yrs) which underwent pterygium surgery at the University Eye Clinic of Cagliari between january 2005 and september 2007. 92 male subjects without pterygium, age matched, were examined as control (mean age 59 ± 10.7 yrs). Normal conjunctival fibroblasts and fibroblasts from G6PD(-) and (+) pterygia were isolated, cultivated, and stimulated in vitro with 10% fetal calf serum (FCS). The expression levels of G6PD mRNA were evaluated by semiquantitative, reverse transcription polymerase chain reaction (RT-PCR). Lipid metabolism was evaluated by 14C-oleate incorporated into cholesterol esters as well as by oil red O staining.
Results: :
Pterygium was observed more frequently in G6PD(-) people (P = 0.004). G6PD(+) pterygium fibroblasts have the highest rate of cell growth, while G6PD(-) the lowest. G6PD mRNA levels are higher in G6PD(-) than G6PD(+) PFs. G6PD(-) PFs show alterations in cholesterol metabolism similar to those observed in G6PD(+) PFs.
Conclusions: :
G6PD(-) individuals have an higher risk of pterygium occurrence than G6PD(+) individuals. UV radiation is known to induce DNA damage and apoptosis by the generation of reactive oxygen species. DNA damage and apoptosis may be a result of increased oxidative stress in G6PD(-) patients. On the other side, although G6PD(-) PFs in vitro demonstrate a low rate of cell growth, in vivo they exhibit a hyperexpression of G6PD gene, with a potential higher production of NADPH, riboses and cholesterol, which can determine an higher risk of fibroblast proliferation.
Keywords: pterygium • oxidation/oxidative or free radical damage • proliferation