Beneficial Effects of Glucagon-Like Peptide-1 (GLP-1) in Diabetes-Induced Retinal Abnormalities: Involvement of Oxidative Stress

Ramos, Hugo; Bogdanov, Patricia; Sampedro, Joel; Huerta, Jordi; Simó, Rafael; Hernández, Cristina

doi:10.3390/antiox9090846

Cited by 24 publications

(26 citation statements)

References 17 publications

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“…There is a demonstrated neuroprotective effect of GLP-1R agonists in both the retina and brain in preclinical studies of ocular hypertension, diabetic retinopathy, Alzheimer's disease, Parkinson's disease, stroke, neuropathy, and several other neurodegenerative diseases (Kastin et al, 2002;McClean et al, 2011;Hao et al, 2012;Fan et al, 2014;Secher et al, 2014;Gonçalves et al, 2016;Zhang et al, 2018Zhang et al, , 2019Basalay et al, 2019;Yang et al, 2019;Chang et al, 2020;Ramos et al, 2020;Ren et al, 2020;Sterling et al, 2020;Zhai et al, 2020). In the retina, GLP-1R agonists have specifically protected retinal ganglion and glia cells, such as the Müller glia, from various stresses (Hao et al, 2012;Fan et al, 2014;Gonçalves et al, 2016;Yang et al, 2019;Ramos et al, 2020;Ren et al, 2020;Sterling et al, 2020) (Figure 2). One of the most promising and effective GLP-1R agonists is semaglutide (Tables 1, 2) (Trujillo et al, 2021), which until September 2019 was only available as an injectable formulation.…”

Section: Oral Semaglutide Has Great Potential For the Prevention Of R...mentioning

confidence: 99%

Glucagon-Like Peptide 1 Receptor Agonists – Potential Game Changers in the Treatment of Glaucoma?

et al. 2022

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Glaucoma is a common ocular neurodegenerative disease characterized by the progressive loss of retinal ganglion cells and their axons. It is the most common cause of irreversible blindness. With an increasing number of glaucoma patients and disease progression despite treatment, it is paramount to develop new and effective therapeutics. Emerging new candidates are the receptor agonists of the incretin hormone glucagon-like-peptide-1 (GLP-1), originally used for the treatment of diabetes. GLP-1 receptor (GLP-1R) agonists have shown neuroprotective effects in preclinical and clinical studies on neurodegenerative diseases in both the brain (e.g., Alzheimer’s disease, Parkinson’s disease, stroke and diabetic neuropathy) and the eye (e.g., diabetic retinopathy and AMD). However, there are currently very few studies investigating the protective effects of GLP-1R agonists in the treatment of specifically glaucoma. Based on a literature search on PubMed, the Cochrane Library, and ClinicalTrials.gov, this review aims to summarize current clinical literature on GLP-1 receptor agonists in the treatment of neurodegenerative diseases to elucidate their potential in future anti-glaucomatous treatment strategies.

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Section: Oral Semaglutide Has Great Potential For the Prevention Of R...mentioning

confidence: 99%

Glucagon-Like Peptide 1 Receptor Agonists – Potential Game Changers in the Treatment of Glaucoma?

et al. 2022

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“…In this section we examine the role of neuropeptides on oxidative stress, the immune response and vascular alterations caused in the diabetic retina. Recently conducted research provides evidence that GLP-1 possesses anti-oxidant capabilities against oxidative stress in the diabetic retina and it is capable of affecting DNA repair and neurogenesis to a certain level in mice ( Ramos et al, 2020 ). With regards to GLP-1RA, exanatide-4 (E4) and other analogs were able to reduce apoptotic damage and ameliorate the decrease in cell numbers in diabetic rat retinas ( Zhang et al, 2011 ; Fan et al, 2014a ).…”

Section: Metabolic Retinal Diseases: Pathology and Neuropeptidesmentioning

confidence: 99%

“…Underproduction of SST during diabetes has also been described ( Carrasco et al, 2007 ), and treatment with SST prevented inflammation, glial activation, and neurodegenerative and functional alterations in db/db mice retinas ( Hernández et al, 2020 ). In db/db mice, the topical administration of GLP-1 has reduced oxidative stress and promoted the repair of DNA damage ( Ramos et al, 2020 ). Furthermore, treatment with the GLP-1RA liraglutide has prevented the upregulation of proapoptotic/proinflammatory signals ( Hernández et al, 2016 ).…”

Section: Metabolic Retinal Diseases: Pathology and Neuropeptidesmentioning

confidence: 99%

Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice

et al. 2022

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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.

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“…(4) Antioxidant properties. GLP-1 eye drops attenuate oxidative stress by increasing the protein levels of glutathione reductase, glutathione peroxidase, CuZnSOD, and MnSOD in diabetic retinas, favoring DNA repair and neuron cells proliferation [ 113 ]. In addition, intravitreal injections of exendin-4 reduces retinal cell death and ROS generation by upregulating Sirt1 and Sirt3 expressions in the retina of early-stage STZ-diabetic rats [ 114 ].…”

Section: Treatment Based On Neuroprotectionmentioning

confidence: 99%

Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy

et al. 2021

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The concept of diabetic retinopathy as a microvascular disease has evolved and is now considered a more complex diabetic complication in which neurovascular unit impairment plays an essential role and, therefore, can be considered as a main therapeutic target in the early stages of the disease. However, neurodegeneration is not always the apparent primary event in the natural story of diabetic retinopathy, and a phenotyping characterization is recommendable to identify those patients in whom neuroprotective treatment might be of benefit. In recent years, a myriad of treatments based on neuroprotection have been tested in experimental models, but more interestingly, there are drugs with a dual activity (neuroprotective and vasculotropic). In this review, the recent evidence concerning the therapeutic approaches targeting neurovascular unit impairment will be presented, along with a critical review of the scientific gaps and problems which remain to be overcome before our knowledge can be transferred to clinical practice.

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Beneficial Effects of Glucagon-Like Peptide-1 (GLP-1) in Diabetes-Induced Retinal Abnormalities: Involvement of Oxidative Stress

Cited by 24 publications

References 17 publications

Glucagon-Like Peptide 1 Receptor Agonists – Potential Game Changers in the Treatment of Glaucoma?

Glucagon-Like Peptide 1 Receptor Agonists – Potential Game Changers in the Treatment of Glaucoma?

Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice

Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy

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