Non‐invasive measurement of steady‐state vitreous lactate concentration

Abstract

The cellular events leading to the proliferation of new preretinal blood vessels into the vitreous are unknown. It has been hypothesized that a metabolic trigger, such as increased lactate concentration, induces ambient growth factors to initiate this neovascularization. However, this hypothesis has not been tested in vivo because non-invasive methods for measuring vitreous lactate concentration have not been available. In this study, we identified lactate as the dominant resonance in normal rabbit vitreous using a water-suppressed, localized proton NMR method; negligible spectral contamination from lipid, alanine and threonine was demonstrated. The steady-state vitreous lactate concentration in vivo was 11.3 +/- 4 mM (mean +/- SD, n = 7 eyes) which was not statistically different (p = 0.498) to the enzymatically determined lactate content in vitreous from a parallel group of animals [12.1 +/- 0.6 mM (n = 6 eyes)]. Non-invasive measurement of steady-state vitreous lactate concentration using localized proton NMR represents the necessary first step in understanding the role of lactate in neovascularization.

Evaluation of corpus geniculatum laterale and vitreous fluid by magnetic resonance spectroscopy in patients with glaucoma; a preliminary study

“…In 1994, MRS was introduced to use in the area of ophthalmology by Berkowitz et al 22 by investigating the lactate concentrations in rabbit vitreous. Subsequently, Rucker et al 23 analysed lactate concentration using MRS in the vitreous of four healthy individuals, and one patient with optic neuropathy.…”

Prognostic MRI biomarkers of treatment efficacy for retinopathy

“…The accuracy and sensitivity of these MRI measurements, relative to standard physiological approaches, have also been validated (8,14,(16)(17)(18)(19)(20). Many of the metrics summarized in Table 1 do not perturb retinal physiology and have been successfully applied to the study of normal and altered retinal health (Table 2).…”

Involvement of the metabolic sensor GPR81 in cardiovascular control

“…The endogenous ligand for GPR81 is lactate (2), a metabolite produced when glycolysis exceeds the capacity to oxidize pyruvate. Lactate acts as an agonist at millimolar concentrations (3), which are achieved systemically under physiologically challenging (4) and pathophysiological circumstances (5) but also locally under unstressed conditions in specific tissues (6)(7)(8)(9)(10). Agonism of GPR81 in adipocytes results in inhibition of lipolysis via the Gi mechanism involving lowering cAMP and downstream dephosphorylation of hormone-sensitive lipase leading to reduced hydrolysis of triglycerides to glycerol and fatty acids (11).…”