title: Oxidative DNA damage and reduced expression of DNA repair genes: Role in primary open angle glaucoma (POAG).
abstract: Controversy exists regarding the role of oxidative DNA damage and DNA repair in primary open angle glaucoma (POAG). We performed a case control study to test the hypothesis that oxidative DNA damage and base excision repair (BER) genes PARP1 and OGG1 are involved in POAG pathogenesis.
  
  
  
  The study included 116 POAG patients and 116 cataract patients as controls. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured by ELISA. RNA was extracted from blood by Trizol and converted to cDNA. The relative quantification of PARP1 and OGG1 genes normalized to β-actin was calculated by the 2-ΔCtmethod. Comparisons between groups were done by student's t-test and correlation between parameters was seen by Pearson correlation coefficient. All p values less than 0.05 were considered significant.
  
  
  
  Mean levels of 8-OHdG were (patients v/s controls) 19.53 ± 1.40 vs. 15.0 ± 2.6 ng/ml in plasma and 8.55 ± 1.94 vs. 5.15 ± 1.09 ng/ml in aqueous humor (p < 0.0001). Expression levels of PARP1 (0.44 ± 0.05 vs. 0.88 ± 0.04) and OGG1 (0.46 ± 0.05 vs. 0.8 ± 0.01) were significantly (p < 0.0001) less in the patients than controls. There was a significant negative correlation between the expression levels of PARP1 and OGG1 with plasma and aqueous 8-OHdG. There was a strong positive correlation between plasma and aqueous 8-OHdG levels.
  
  
  
  These results support our hypothesis that oxidative stress-induced DNA damage is associated with POAG. Increased oxidative DNA damage in POAG may be attributed to decreased expression of DNA repair enzymes of the BER pathway.
authors.affiliation: a Department of Ophthalmology , Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Mohanty
authors.affiliation: b Department of Anatomy , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Rima
authors.initials: R
authors.lastname: Dada
authors.affiliation: a Department of Ophthalmology , Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Tanuj
authors.initials: T
authors.lastname: Dada
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000199:Actins / Q000235:genetics; D001082:Aqueous Humor / Q000378:metabolism; D016022:Case-Control Studies; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005902:Glaucoma, Open-Angle / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000199:Actins; D000080242:8-Hydroxy-2'-Deoxyguanosine; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D003849:Deoxyguanosine
keywords: 8-hydroxy-2′-deoxyguanosine (8-OHdG); 8-oxoguanine DNA glycosylase (OGG1); glaucoma; oxidative stress; poly (ADP-ribose) polymerase 1 (PARP1)