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.

Daytime Lipid Metabolism Modulated by CLOCK Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma

“…All patients were examined and diagnosed under the supervision of the State Autonomous Health Institution of the Tyumen Region "Regional Ophthalmological Dispensary" during 2013-2016. The current findings are based on data from a previously published cross-sectional study [17,19,20].…”

“…Patients with S-POAG and A-POAG were matched by gender, age, and treatment. Exclusion criteria were described previously [17,19,20].…”

“…Genotyping was always performed by the same operator, who was not aware of the participant's clinical characteristics. Saliva samples were collected via standard protocols from nineteen patients as described elsewhere [17,19]. Polymorphic gene variants were identified by SNP (single nucleotide polymorphism) Screen Kit (Syntol; Moscow, Russia) for eight genes (clock genes: PER2 rs6431590, PER3 VNTR, CLOCK rs1801260 3111T/C, cryptochrome CRY1 rs12820777; melatonin receptor genes MTNR1A rs34532313, MTNR1B rs10830963, G-protein GNB rs5443; and angiotensin converting enzyme, ACE rs1799752 insertion/deletion).…”

“…One factor that causes deterioration in circadian rhythms is glaucomatous damage to retinal ganglion cells (RGCs), which compromises light perception and signal transduction to the master clock (suprachiasmatic nuclei in the brain). RGC damage was found to be associated with disrupted local [16,17] and systemic [18][19][20][21] circadian rhythms, as well as sleep [22,23]. Circadian rhythms of lipid metabolism are modulated by light and food [5][6][7][8][9][10][11][12][13][14][15].…”

An Update on Pharmacotherapy of Glaucoma

“…The circadian rhythm of IOP is controlled in the suprachiasmatic nucleus [75]. In glaucomatous eyes, the diurnal phasic variation of IOP seems to be dysregulated [76,77]. Short-term IOP fluctuation has been associated with glaucoma progression [78].…”