Dataset Information

Spatial distribution of metabolites in the retina and its relevance to studies of metabolic retinal disorders.

ABSTRACT:

Introduction

The primate retina has evolved regional specialisations for specific visual functions. The macula is specialised towards high acuity vision and is an area that contains an increased density of cone photoreceptors and signal processing neurons. Different regions in the retina display unique susceptibility to pathology, with many retinal diseases primarily affecting the macula.

Objectives

To better understand the properties of different retinal areas we studied the differential distribution of metabolites across the retina.

Methods

We conducted an untargeted metabolomics analysis on full-thickness punches from three different regions (macula, temporal peri-macula and periphery) of healthy primate retina.

Results

Nearly half of all metabolites identified showed differential abundance in at least one comparison between the three regions. Furthermore, mapping metabolomics results from macula-specific eye diseases onto our region-specific metabolite distributions revealed differential abundance defining systemic metabolic dysregulations that were region specific.

Conclusions

The unique metabolic phenotype of different retinal regions is likely due to the differential distribution of different cell types in these regions reflecting the specific metabolic requirements of each cell type. Our results may help to better understand the pathobiology of retinal diseases with region specificity.

SUBMITTER: Bonelli R

PROVIDER: S-EPMC9902429 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Spatial distribution of metabolites in the retina and its relevance to studies of metabolic retinal disorders.

Bonelli Roberto R Woods Sasha M SM Lockwood Sarah S Bishop Paul N PN Khan Kamron N KN Bahlo Melanie M Ansell Brendan R E BRE Fruttiger Marcus M

Metabolomics : Official journal of the Metabolomic Society 20230206 2

<h4>Introduction</h4>The primate retina has evolved regional specialisations for specific visual functions. The macula is specialised towards high acuity vision and is an area that contains an increased density of cone photoreceptors and signal processing neurons. Different regions in the retina display unique susceptibility to pathology, with many retinal diseases primarily affecting the macula.<h4>Objectives</h4>To better understand the properties of different retinal areas we studied the diff ...[more]

PMID: 36745234

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Project description:The mammalian retina contains approximately 30 neuropeptides that are synthetized by different neuronal cell populations, glia, and the pigmented epithelium. The presence of these neuropeptides leaves a mark on normal retinal molecular processes and physiology, and they are also crucial in fighting various pathologies (e.g., diabetic retinopathy, ischemia, age-related pathologies, glaucoma) because of their protective abilities. Retinal pathologies of different origin (metabolic, genetic) are extensively investigated by genetically manipulated in vivo mouse models that help us gain a better understanding of the molecular background of these pathomechanisms. These models offer opportunities to manipulate gene expression in different cell types to help reveal their roles in the preservation of retinal health or identify malfunction during diseases. In order to assess the current status of transgenic technologies available, we have conducted a literature survey focused on retinal disorders of metabolic origin, zooming in on the role of retinal neuropeptides in diabetic retinopathy and ischemia. First, we identified those neuropeptides that are most relevant to retinal pathologies in humans and the two clinically most relevant models, mice and rats. Then we continued our analysis with metabolic disorders, examining neuropeptide-related pathways leading to systemic or cellular damage and rescue. Last but not least, we reviewed the available literature on genetically modified mouse strains to understand how the manipulation of a single element of any given pathway (e.g., signal molecules, receptors, intracellular signaling pathways) could lead either to the worsening of disease conditions or, more frequently, to substantial improvements in retinal health. Most attention was given to studies which reported successful intervention against specific disorders. For these experiments, a detailed evaluation will be given and the possible role of converging intracellular pathways will be discussed. Using these converging intracellular pathways, curative effects of peptides could potentially be utilized in fighting metabolic retinal disorders.

Dataset Information

Spatial distribution of metabolites in the retina and its relevance to studies of metabolic retinal disorders.

Introduction

Objectives

Methods

Results

Conclusions

Publications

Spatial distribution of metabolites in the retina and its relevance to studies of metabolic retinal disorders.

Similar Datasets

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