Dataset Information

Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma.

ABSTRACT: Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of "marker" circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, opposite to the daytime phase position in S-POAG patients (p < 0.0001). The 24-h IOP phase correlated with RGC loss (p < 0.0001). The internal phase shift between IOP and body temperature gradually increased with POAG progression (p < 0.001). Angiotensin converting enzyme Alu-repeat deletion/insertion (ACE I/D) emerged as a candidate gene polymorphism, which may play a role in the alteration of the circadian IOP variability in advanced glaucoma. To conclude, a reliable estimation of the 24-h rhythm in IOP requires the degree of RGC damage to be assessed. In advanced POAG, the 24-h phase of IOP tended to occur during the night and correlated with RGC loss, being progressively delayed relative to the phase of temperature.

SUBMITTER: Neroev V

PROVIDER: S-EPMC7795318 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma.

Neroev Vladimir V Malishevskaya Tatyana T Weinert Dietmar D Astakhov Sergei S Kolomeichuk Sergey S Cornelissen Germaine G Kabitskaya Yana Y Boiko Elena E Nemtsova Irina I Gubin Denis D

International journal of molecular sciences 20201231 1

Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of "marker" circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, ...[more]

PMID: 33396443

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Project description:Glaucoma can result in retinal ganglion cell (RGC) death and permanently damaged vision. Pathologically high intraocular pressure (ph-IOP) is the leading cause of damaged vision during glaucoma; however, controlling ph-IOP alone does not entirely prevent the loss of glaucomatous RGCs, and the underlying mechanism remains elusive. In this study, we reported an increase in ferric iron in patients with acute primary angle-closure glaucoma (the most typical glaucoma with ph-IOP damage) compared with the average population by analyzing free iron levels in peripheral serum. Thus, iron metabolism might be involved in regulating the injury of RGCs under ph-IOP. In vitro and in vivo studies confirmed that ph-IOP led to abnormal accumulation of ferrous iron in cells and retinas at 1-8 h post-injury and elevation of ferric iron in serum at 8 h post-injury. Nuclear receptor coactivator 4 (NCOA4)-mediated degradation of ferritin heavy polypeptide 1(FTH1) is essential to disrupt iron metabolism in the retina after ph-IOP injury. Furthermore, knockdown of Ncoa4 in vivo inhibited FTH1 degradation and reduced the retinal ferrous iron level. Elevated ferrous iron induced by ph-IOP led to a marked accumulation of pro-ferroptotic factors (lipid peroxidation and acyl CoA synthetase long-chain family member 4) and a depletion of anti-ferroptotic factors (glutathione, glutathione peroxidase 4, and nicotinamide adenine dinucleotide phosphate). These biochemical changes resulted in RGC ferroptosis. Deferiprone can pass through the blood-retinal barrier after oral administration and chelated abnormally elevated ferrous iron in the retina after ph-IOP injury, thus inhibiting RGC ferroptosis and protecting visual function. In conclusion, this study revealed the role of NCOA4-FTH1-mediated disturbance of iron metabolism and ferroptosis in RGCs during glaucoma. We demonstrate the protective effect of Deferiprone on RGCs via inhibition of ferroptosis, providing a research direction to understand and treat glaucoma via the iron homeostasis and ferroptosis pathways.

Project description:Importance:Twenty-four-hour intraocular pressure (IOP) patterns may provide more information regarding rates of visual field progression than office-hour measurements. However, little is known about the added value of 24-hour monitoring when stratifying glaucoma risk based on rates of progression. Objective:To test the hypothesis that 24-hour IOP-related patterns recorded with a contact lens sensor (CLS) correlate with prior rates of visual field progression. Design, Setting, and Participants:A multicenter, retrospective cohort study was conducted at 50 ophthalmology care centers in 13 countries. Participants included 445 patients (445 eyes) with treated, manifest open-angle glaucoma. The study was conducted from November 8, 1999, to September 17, 2016. Interventions:Twenty-four-hour recordings of IOP-related patterns were prospectively collected with a CLS system. Retrospective visual field data of patients who underwent at least 3 prior reliable visual field tests were examined. Main Outcomes and Measures:Association between CLS variables and rates of visual field mean deviation (MD) change. Results:Of the 445 patients included, 238 (53.5%) were women and 394 (88.5%) were white. The mean (SD) age and MD values at the time of CLS recording were 68.9 (11.2) years and -9.0 (7.0) dB. The mean rate of MD change was -0.46 (0.5) dB/y in 5.2 (3) years of follow-up. After adjusting for baseline MD severity, age, and treatment, the following CLS variables were associated with fast visual field progression: mean peak ratio while awake (??=?-0.021; 95% CI, -0.04 to -0.003), number of long peaks during sleep (??=?0.036; 95% CI, 0.005 to 0.067), night bursts ocular pulse frequency SD (??=?0.027; 95% CI, 0.004 to 0.051), and night bursts ocular pulse amplitude SD (??=?19.739; 95% CI, 1.333 to 38.145). Regression models including CLS variables had better fit than Goldmann IOP when testing the association with rates of progression. Conclusions and Relevance:Results of this study indicate that 24-hour CLS recordings may be associated with prior rates of visual field progression of glaucoma. This association appears to be better than Goldmann mean IOP measured multiple times during office hours. Therefore, the CLS may be useful to assess the risk of future functional loss, even in situations when insufficient historical visual field information is available.

Dataset Information

Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma.

Publications

Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma.

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