The gut-retina axis: a new perspective in the prevention and treatment of diabetic retinopathy

Zhang, Haiyan; Mo, Ya

doi:10.3389/fendo.2023.1205846

Cited by 5 publications

(3 citation statements)

References 139 publications

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“…The pathobiological processes contributing to the development of diabetic retinopathy (DR) are multifaceted and involve intricate cellular and molecular mechanisms. These mechanisms encompass hyperglycemia-triggered oxidative stress, inflammation, PKC pathways, microbiota alterations, and imbalances in HSPCs [31][32][33]. Among these, NOD-like receptors (NLRs), including NOD1, NLRP1, and NLRP3, serve as vital interfaces between microbiota and systemic chronic inflammation.…”

Section: Discussionmentioning

confidence: 99%

NOD1 deficiency ameliorates the progression of diabetic retinopathy by modulating bone marrow–retina crosstalk

Qiu,

Wu,

Chen

et al. 2024

Stem Cell Res Ther

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Background Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) plays a pivotal role in inducing metabolic inflammation in diabetes. Additionally, the NOD1 ligand disrupts the equilibrium of bone marrow-derived hematopoietic stem/progenitor cells, a process that has immense significance in the development of diabetic retinopathy (DR). We hypothesized that NOD1 depletion impedes the advancement of DR by resolving bone marrow dysfunction. Methods We generated NOD1−/−-Akita double-mutant mice and chimeric mice with hematopoietic-specific NOD1 depletion to study the role of NOD1 in the bone marrow–retina axis. Results Elevated circulating NOD1 activators were observed in Akita mice after 6 months of diabetes. NOD1 depletion partially restored diabetes-induced structural changes and retinal electrical responses in NOD1−/−-Akita mice. Loss of NOD1 significantly ameliorated the progression of diabetic retinal vascular degeneration, as determined by acellular capillary quantification. The preventive effect of NOD1 depletion on DR is linked to bone marrow phenotype alterations, including a restored HSC pool and a shift in hematopoiesis toward myelopoiesis. We also generated chimeric mice with hematopoietic-specific NOD1 ablation, and the results further indicated that NOD1 had a protective effect against DR. Mechanistically, loss of hematopoietic NOD1 resulted in reduced bone marrow-derived macrophage infiltration and decreased CXCL1 and CXCL2 secretion within the retina, subsequently leading to diminished neutrophil chemoattraction and NETosis. Conclusions The results of our study unveil, for the first time, the critical role of NOD1 as a trigger for a hematopoietic imbalance toward myelopoiesis and local retinal inflammation, culminating in DR progression. Targeting NOD1 in bone marrow may be a potential strategy for the prevention and treatment of DR.

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Section: Discussionmentioning

confidence: 99%

NOD1 deficiency ameliorates the progression of diabetic retinopathy by modulating bone marrow–retina crosstalk

Qiu,

Wu,

Chen

et al. 2024

Stem Cell Res Ther

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“…Studies on the interaction between the ocular and intestinal microbiota have increased in recent years. Some researchers hypothesize the existence of a gut-eye "axis": the alteration of the intestinal microbiota seems to be linked to some eye diseases, including uveitis, macular degeneration, and glaucoma [179][180][181][182]. Most microorganisms are located in the intestine, especially in the ascending colon: therefore, we can find bacteria, fungi, viruses, and helminths in constant symbiotic relationship with our immune system and with numerous functions, such as metabolic, protective, of immune education, and of vitamin production [183].…”

Section: Gut-eye Axismentioning

confidence: 99%

Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions

Caruso,

Fields,

Rimondi

et al. 2024

IJMS

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The human retina is a complex anatomical structure that has no regenerative capacity. The pathogenesis of most retinopathies can be attributed to inflammation, with the activation of the inflammasome protein platform, and to the impact of oxidative stress on the regulation of apoptosis and autophagy/mitophagy in retinal cells. In recent years, new therapeutic approaches to treat retinopathies have been investigated. Experimental data suggest that the secretome of mesenchymal cells could reduce oxidative stress, autophagy, and the apoptosis of retinal cells, and in turn, the secretome of the latter could induce changes in mesenchymal cells. Other studies have evidenced that noncoding (nc)RNAs might be new targets for retinopathy treatment and novel disease biomarkers since a correlation has been found between ncRNA levels and retinopathies. A new field to explore is the interaction observed between the ocular and intestinal microbiota; indeed, recent findings have shown that the alteration of gut microbiota seems to be linked to ocular diseases, suggesting a gut–eye axis. To explore new therapeutical strategies for retinopathies, it is important to use proper models that can mimic the complexity of the retina. In this context, retinal organoids represent a good model for the study of the pathophysiology of the retina.

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“…Currently, numerous studies have demonstrated a connection between the metabolism of intestinal microorganisms and retinal diseases, so the concept of the gut-retinal axis has been proposed by scholars ( 7 ). The gut microbiota has been found to influence the expansion of various retinal disorders, including diabetic retinopathy, optic neuritis, age-related macular degeneration, and retinopathy of prematurity.…”

Section: Introductionmentioning

confidence: 99%

Mendelian randomization study and mediation analysis about the relation of inflammatory bowel disease and diabetic retinopathy: the further exploration of gut-retina axis

Lin,

Cheng,

et al. 2024

Front. Endocrinol.

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BackgroundThe concept of the gut-retinal axis proposed by previous scholars primarily focused on the relationship between intestinal microbiota and retinal diseases, and few further expanded the relationship between intestinal diseases and retinal diseases. To further substantiate the concept of the gut-retinal axis, we analyzed inflammatory bowel disease (IBD) and diabetic retinopathy (DR) using Mendelian randomization (MR), and use mediation analysis to further explore the potential substances that influence this causal relationship.MethodsThe genome-wide association study’s (GWAS) summary statistics for genetic variations were utilized in a Mendelian randomization (MR) investigation. GWAS data on IBD (including ulcerative colitis (UC), Crohn’s disease (CD), and IBD) for non-Finnish Europeans (NFE) were sourced from published articles. In contrast, data on DR (including DR and diabetic maculopathy (DMP)) were obtained from FinnGen R9. The causal relationship has been investigated using inverse variance weighted (IVW), MR-Egger, and weighted median and sensitivity analysis was applied to verify the stability of the results. In addition, we applied mediation analysis to investigate whether circulating inflammatory proteins and plasma lipids played a mediating role, and calculated its effect ratio.ResultsThe causal relationship between IBD and DR was discovered by employing the inverse variance weighted (IVW) method and weighted median method. In forward MR, UC was significantly associated with lower risk of DR (IVW: OR=0.874; 95%CI= 0.835–0.916; P value= 1.28E-08) (Weighted median: OR=0.893; 95%CI= 0.837–0.954; P value= 7.40E-04). In reverse MR, it was shown that DR (IVW: OR=0.870; 95%CI= 0.828–0.914; P value= 2.79E-08)(Weighted median: OR=0.857; 95%CI= 0.801–0.916; P value= 6.40E-06) and DMP (IVW: OR=0.900; 95%CI= 0.865–0.937; P value= 3.34E-07)(Weighted median: OR=0.882; 95%CI= 0.841–0.924; P value= 1.82E-07) could reduce the risk of CD. What’s more, DR is associated with a lower risk of IBD according to genetic prediction (IVW: OR=0.922; 95%CI= 0.873–0.972; P value= 0.002) (Weighted median: OR=0.924; 95%CI= 0.861–0.992; P value= 0.029). Fibroblast growth factor 21 (FGF21), phosphatidylcholine (PC), and triacylglycerol (TG) serve as mediators in these relationships.ConclusionsOur research offers novel insights and sources for investigating the gut-retina axis in the genetic relationship between IBD and DR. We discover four mediators and more about the association between the intestine and retinal disorders and provide more evidence for the gut-retinal axis theory.

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The gut-retina axis: a new perspective in the prevention and treatment of diabetic retinopathy

Cited by 5 publications

References 139 publications

NOD1 deficiency ameliorates the progression of diabetic retinopathy by modulating bone marrow–retina crosstalk

NOD1 deficiency ameliorates the progression of diabetic retinopathy by modulating bone marrow–retina crosstalk

Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions

Mendelian randomization study and mediation analysis about the relation of inflammatory bowel disease and diabetic retinopathy: the further exploration of gut-retina axis

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