Oxidative DNA damage and reduced expression of DNA repair genes: Role in primary open angle glaucoma (POAG)
Abstract
Background: 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.Materials and Methods: 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−ΔCt method. 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.Results: 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.Conclusion: 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.
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Reduced expression of DNA repair genes due to increased levels of oxidative stress has been implicated in several other human diseases, including diabetes, obesity, and glaucoma.
“In fact, reduced expression of DNA repair genes due to increased levels of oxidative stress has been implicated with several other human diseases, including diabetes [84], obesity [137], and glaucoma [109].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [109]
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- Authors
- Mohanty, K., Dada, R., & Dada, T.
- Affiliations
- All India Institute of Medical Sciences (IN)
- Corresponding author
- Dada, Tanuj
- Venue
- Ophthalmic Genetics
- Publisher
- Informa UK Limited
- Published
- 2017-01-27
- Volume
- 38
- Issue
- 5
- Pages
- 446-450
- ISSN
- 1381-6810 (ISSN-L)
- 1744-5094
- OpenAlex
- W2581806993
- Cited by
- 30
- References
- 35
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 2
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ophthalmic Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Indian Council of Medical Research (IR-440)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
- Keywords
- primary open-angle glaucoma, oxidative DNA damage, base excision repair, PARP1, OGG1, 8-hydroxy-2'-deoxyguanosine, aqueous humor, oxidative stress, DNA repair gene expression, glaucoma pathogenesis
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, 8-Hydroxy-2'-Deoxyguanosine, Actins, Aqueous Humor, Deoxyguanosine, DNA Damage, DNA Repair, Enzyme-Linked Immunosorbent Assay, Female, Glaucoma, Open-Angle, Humans, Male, Middle Aged, Case-Control Studies, Oxidative Stress, DNA Glycosylases, Real-Time Polymerase Chain Reaction
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