Potential metabolic markers in glaucoma and their regulation in response to hypoxia

Abstract

Purpose: To assess novel differences in serum levels of glucose, lactate and amino acids in patients with normal-tension glaucoma (NTG) compared to agematched controls, at baseline and in response to universal hypoxia. Methods: Twelve patients diagnosed with NTG and eleven control subjects underwent normobaric hypoxia for 2 hr. Peripheral venous blood samples were taken at baseline, during hypoxia and in the recovery phase. Serum glucose and lactate levels were measured by a blood gas analyser. Amino acids were analysed by high-performance liquid chromatography. Results: Baseline levels of lactate and total amino acids were significantly lower in patients with NTG compared to healthy controls. No differences were seen in blood glucose levels between the two groups. Lactate levels remained unchanged during hypoxia in the control group, but increased in patients with NTG. In the recovery phase, total amino acid levels were reduced in the control group, whereas no changes were found in patients with NTG. Conclusion: Reduced serum levels of lactate and total amino acids were identified as potential markers for NTG. Moreover, significant differential regulatory patterns of certain amino acids were found in patients with NTG compared to control subjects. Overall, our results suggest a link between systemic energy metabolites and NTG and support a novel understanding of glaucoma as an inner retinal manifestation of a systemic condition.

Increased Antioxidant Capacity and Pro-Homeostatic Lipid Mediators in Ocular Hypertension—A Human Experimental Model

“…A direct power calculation based on former studies was not possible as previous studies only included one test group [ 29 , 30 , 31 ]. Furthermore, we were unable to perform a power calculation based on previously published data [ 32 ] as two study groups were included in this study. Power and sample size calculations were therefore performed based on a previous study [ 33 ] on arterial vessel diameters as a parallel project that measured retinal vessel diameters during hypoxia.…”

“…The number of IOP measurements before inclusion varied in the NTG group, but all patients had information on IOP prior to treatment, and at least six IOP measurements were performed before enrollment in the study. Inclusion criteria for patients with NTG were as follows: untreated IOP below 21 mmHg measured at different times of the day (8 a.m.–5 p.m.); open angles determined by gonioscopy; optic disc cupping, characterized by a violated ISNT rule (normal eyes show a characteristic configuration for disc rim thickness of inferior ≥ superior ≥ nasal ≥ temporal); glaucomatous visual field loss identified by Humphrey or Octopus perimetry, and significant nerve fiber loss detected by ocular coherence tomography (OCT) [ 32 ]. Inclusion criteria for OHT patients were as follows: untreated IOP above 24 mmHg measured at different times of the day (8 a.m.–5 p.m.); open angles determined by gonioscopy; no signs of optic disc cupping; normal visual fields, and normal OCT [ 32 ].…”

“…Inclusion criteria for patients with NTG were as follows: untreated IOP below 21 mmHg measured at different times of the day (8 a.m.–5 p.m.); open angles determined by gonioscopy; optic disc cupping, characterized by a violated ISNT rule (normal eyes show a characteristic configuration for disc rim thickness of inferior ≥ superior ≥ nasal ≥ temporal); glaucomatous visual field loss identified by Humphrey or Octopus perimetry, and significant nerve fiber loss detected by ocular coherence tomography (OCT) [ 32 ]. Inclusion criteria for OHT patients were as follows: untreated IOP above 24 mmHg measured at different times of the day (8 a.m.–5 p.m.); open angles determined by gonioscopy; no signs of optic disc cupping; normal visual fields, and normal OCT [ 32 ]. Exclusion criteria for all participants were as follows: a medical history of ocular trauma; competing eye conditions other than glaucoma affecting the optic nerve; significant systemic diseases, i.e., dysregulated hypertension, heart failure, hypercholesterolemia, diabetes mellitus, autoimmune diseases, and previous cerebral infarct or hemorrhage; subjects who could not contribute with the experimental setup; subjects under 50 years of age, and subjects who smoked at the time of inclusion.…”

“…Before hypoxic intervention, participants received pupil dilating drops. The intervention with hypoxia has previously been described by Vohra et al [ 32 ]. Briefly, each participant was exposed to normobaric hypoxia for two hours through a tightly fitting facemask attached to a non-breathable valve followed by normobaric normoxia by normal breathing in a supine position.…”

Lactate-Mediated Protection of Retinal Ganglion Cells

“…Our study may suggest that compromised lactate-facilitated neuroprotection may potentially be involved in the development of inner retinal diseases, in which the RGCs are dying. One of the most predominant inner retinal diseases is glaucoma, and a recent study revealed that patients with normal tension glaucoma had lower systemic blood lactate levels compared with age-matched healthy controls [54]. This supports the idea of a potential involvement of lactate in retinal neurodegeneration, which may consequently alter visual perception.…”