# Metabolomics of Ocular Tissues with High and Low Metabolic Activity

## TL;DR

This study finds that both the eye's lens and retina have high ATP levels, which may help prevent protein clumping linked to eye diseases.

## Contribution

The study reveals similar high NTP concentrations and metabolic health in metabolically distinct eye tissues.

## Key findings

- The lens and retina both have high NTP concentrations (≥2.3 mM and 2.4 mM, respectively).
- The PSM values for the lens and retina are similar (1.28 and 1.42), indicating comparable metabolic health.
- High NTP levels may act as hydrotropes to prevent protein aggregation in age-related eye diseases.

## Abstract

This report uses 31P nuclear magnetic resonance spectroscopy to study metabolomics focusing on adenosine triphosphate (ATP), nucleoside triphosphates (NTP), and the 31P spectral modulus in the crystalline lens and sensory retina.

An unexplainably high millimolar concentration of adenosine triphosphate (ATP) exists in the crystalline lens which is similar to that found in the retina. This observation is perplexing because the lens is one of the most metabolically quiescent tissues in the body, whereas the retina is one of the most metabolically active tissues in the body.

This study compares phosphorus metabolomics and related metabolic indices in the crystalline lens and retina measuring their metabolic health status.

The 31P spectral modulus, a measure of overall metabolic health status, is similar in both the lens and the retina.

These are novel findings addressing the metabolomics of phosphate metabolism associated with metabolically diverse eye tissues.

The high mM nucleoside triphosphate concentration in the lens and retina is hypothesized to function as a hydrotrope, preventing the protein aggregation that results in age-related cataractogenesis and macular degeneration.

Background/Objectives: An unexplainably high millimolar (~3 mM) concentration of adenosine triphosphate (ATP), herein designated as nucleoside triphosphate (NTP), exists in the crystalline lens even though all of the known functions of NTP combined require only micromolar (μM) concentrations. Since the lens is one of the most metabolically quiescent tissues in the body and the retina is one of the most metabolically active tissues in the body, we compared their phosphorus metabolomics and related metabolic indices that measure their metabolic health status. As such, the purpose of this report was to compare the NTP concentrations in lenticular and retinal tissues and the metabolic indices that include NTP as well as their phosphorus-31 spectral modulus (PSM). Methods: Known phosphatic metabolic profiles of rat lenses and retinas were compared and quantified in mole % phosphorus using phosphorus-31 nuclear magnetic resonance spectroscopy. Metabolic indices measuring health status, where ATP is a principal component, were calculated, including the PSM. Results: In this secondary analysis, the NTP concentration calculated in the lens was 41.0% of the total phosphate detected, whereas it was similarly 37.6% in the sensory retina. The PSM values were 1.28 for the lens and similarly 1.42 for the retina. Conclusions: Due to the lens tissue’s low quiescent metabolic activity, one might expect the NTP concentration to be lower in the lens than in the highly metabolically active retina: a similar difference is expected in the PSM. However, this was not the case with the mM concentrations of NTP in both the lens (≥2.3 mM) and the retina (2.4 mM). The similarly high mM NTP concentration coupled with the PSM-calculated measure of metabolic health in these tissues is a novel finding. The novel findings of such similarly high concentrations of NTP in these metabolically diverse eye tissues further support and are consistent with the hypothesized role of NTP as a hydrotrope, preventing protein aggregation resulting in age-related cataractogenesis and age-related macular degeneration.