Neuroprotective Peptides in Retinal Disease

Cervia, Davide; Catalani, Elisabetta; Casini, G.

doi:10.3390/jcm8081146

Cited by 25 publications

(22 citation statements)

References 260 publications

(336 reference statements)

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“…Neuropeptides and their receptors are widely expressed in mammalian retinas, where they exert multifaceted functions both during development and in the mature animal (Bagnoli et al, 2003). In particular, some of them may exert important roles in retinal diseases (Gabriel, 2013; Cervia et al, 2019).…”

Section: Neuropeptidesmentioning

confidence: 99%

“…Neuroprotective effects of GLP-1R activation have been demonstrated in a rat model of optic nerve crush, where intravitreal implants of beads with genetically modified cells producing GLP-1 decreased apoptosis and promoted survival of retinal ganglion cells (Zhang R. et al, 2011), and in diabetic rats, where exendin-4, an analog of GLP-1, protected from oxidative stress from apoptotic cell death and ameliorated retinal function as assessed with ERG (Zhang et al, 2009; Zhang Y. et al, 2011; Fan et al, 2014b; Zeng et al, 2016; Cai et al, 2017; Cervia et al, 2019). Most importantly, both neuroprotective and vasoprotective effects of GLP-1 agonists have been described in models of retinal diseases.…”

Section: Neuropeptidesmentioning

confidence: 99%

“…A local RAS is present in the retina, where RAS components have been localized to different retinal cell types, including retinal neurons and Müller cells (Wilkinson-Berka et al, 2012). A variety of studies have shown that reduction of AngII expression or blockade of AT1R on the one hand, or stimulation of ACE2 on the other, may reduce the retinal damage occurring in retinal pathologies, such as glaucoma, retinal ischemia, autoimmune uveitis, or DR (Cervia et al, 2019).…”

Section: Neuropeptidesmentioning

confidence: 99%

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Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

2019

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Diabetic retinopathy (DR) is a common complication of diabetes and constitutes a major cause of vision impairment and blindness in the world. DR has long been described exclusively as a microvascular disease of the eye. However, in recent years, a growing interest has been focused on the contribution of neuroretinal degeneration to the pathogenesis of the disease, and there are observations suggesting that neuronal death in the early phases of DR may favor the development of microvascular abnormalities, followed by the full manifestation of the disease. However, the mediators that are involved in the crosslink between neurodegeneration and vascular changes have not yet been identified. According to our hypothesis, vascular endothelial growth factor (VEGF) could probably be the most important connecting link between the death of retinal neurons and the occurrence of microvascular lesions. Indeed, VEGF is known to play important neuroprotective actions; therefore, in the early phases of DR, it may be released in response to neuronal suffering, and it would act as a double-edged weapon inducing both neuroprotective and vasoactive effects. If this hypothesis is correct, then any retinal stress causing neuronal damage should be accompanied by VEGF upregulation and by vascular changes. Similarly, any compound with neuroprotective properties should also induce VEGF downregulation and amelioration of the vascular lesions. In this review, we searched for a correlation between neurodegeneration and vasculopathy in animal models of retinal diseases, examining the effects of different neuroprotective substances, ranging from nutraceuticals to antioxidants to neuropeptides and others and showing that reducing neuronal suffering also prevents overexpression of VEGF and vascular complications. Taken together, the reviewed evidence highlights the crucial role played by mediators such as VEGF in the relationship between retinal neuronal damage and vascular alterations and suggests that the use of neuroprotective substances could be an efficient strategy to prevent the onset or to retard the development of DR.

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Section: Neuropeptidesmentioning

confidence: 99%

Section: Neuropeptidesmentioning

confidence: 99%

Section: Neuropeptidesmentioning

confidence: 99%

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Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

2019

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“… 44 Furthermore, the glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted by the gastrointestinal tract in response to food, has shown neuroprotective effects for retinal ganglion cells. 45 Extending the duration of feeding in early weaned animals could lead to increases in GLP-1.…”

Section: Discussionmentioning

confidence: 99%

A Ketogenic & Low-Protein Diet Slows Retinal Degeneration in rd10 Mice

Ryals

Huang

Wafai

et al. 2020

Trans. Vis. Sci. Tech.

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Treatments that delay retinal cell death regardless of genetic causation are needed for inherited retinal degeneration (IRD) patients. The ketogenic diet is a high-fat, low-carbohydrate diet, used to treat epilepsy, and has beneficial effects for neurodegenerative diseases. This study aimed to determine whether the ketogenic diet could slow retinal degeneration. Methods: Early weaned, rd10 and wild-type (WT) mice were placed on either standard chow, a ketogenic diet, or a ketogenic & low-protein diet. From postnatal day (PD) 23 to PD50, weight and blood β-hydroxybutyrate levels were recorded. Retinal thickness, retinal function, and visual performance were measured via optical coherence tomography, electroretinography (ERG), and optokinetic tracking (OKT). At PD40, serum albumin, rhodopsin protein, and phototransduction gene expression were measured. Results: Both ketogenic diets elicited a systemic induction of ketosis. However, rd10 mice on the ketogenic & low-protein diet had significant increases in photoreceptor thickness, ERG amplitudes, and OKT thresholds, whereas rd10 mice on the ketogenic diet showed no photoreceptor preservation. In both rd10 and WT mice, the ketogenic & low-protein diet was associated with abnormal weight gain and decreases in serum albumin levels, 27% and 56%, respectively. In WT mice, the ketogenic & low-protein diet was also associated with an ∼20% to 30% reduction in ERG amplitudes. Conclusions: The ketogenic & low-protein diet slowed retinal degeneration in a clinically relevant IRD model. In WT mice, the ketogenic & low-protein diet was associated with a decrease in phototransduction and serum albumin, which could serve as a protective mechanism in the rd10 model. Although ketosis was associated with protection, its role remains unclear. Translational Relevance: Neuroprotective mechanisms associated with the ketogenic & low-protein diet have potential to slow retinal degeneration.

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“…Diabetic retinopathy (DR) is a complication of diabetes that represents one of the major causes of vision loss in humans. The endogenous neuropeptide somatostatin has been widely studied for its powerful neuroprotective properties that may be exploited for DR treatment, and these studies have been extensively reviewed (Gabriel, 2013;Hernandez et al, 2014;Szabadfi et al, 2014;Simo-Servat et al, 2018;Cervia et al, 2019). In particular, the treatment with the somatostatin analog octreotide (OCT) has been found to inhibit apoptotic cell death and avoid vascular endothelial growth factor (VEGF) overexpression in retinal explants exposed to typical diabetic stressors such as hyperglycemia, oxidative stress (OS) or advanced glycation end-products (Amato et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy

Amato

Giannaccini

Monte

et al. 2020

Front. Bioeng. Biotechnol.

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The somatostatin analog octreotide (OCT) displays important neuroprotective and antiangiogenic properties that could make it an interesting candidate to treat diabetic retinopathy (DR). Unfortunately, systemic drug administration is hindered by severe side effects, therefore topical administration routes are preferable. However, drug delivery through eye drops may be difficult due to ocular barriers and, in the long term, could induce ocular damage. On the other hand, intraocular injections must be repeated to maintain drug concentration, and this may cause severe damage to the eye. To decrease injection frequency, long-term release and reduced biodegradation could be obtained by binding the drug to biodegradable polymeric nanoparticles. In the present study, we made a preparation of OCT bound to magnetic nanoparticles (MNP-OCT) and tested its possible use as an OCT delivery system to treat retinal pathologies such as DR. In particular, in vitro, ex vivo, and in vivo experimental models of the mammalian retina were used to investigate the possible toxicity of MNPs, possible effects of the binding to MNPs on OCT bioactivity, and the localization of MNP-OCT in the retina after intraocular injection. The results showed that, both in human retinal endothelial cells (HRECs) and in mouse retinal explants, MNPs were not toxic and the binding with MNPs did not influence OCT antiangiogenic or antiapoptotic activity. Rather, effects of MNP-OCT were observed at concentrations up to 100-fold (in HRECs) or 10-fold (in mouse retinal explants) lower compared to OCT, indicating that OCT bioactivity was enhanced in MNP-OCT. MNP-OCT in mouse retinas in vivo after intraocular delivery were initially localized mainly to the outer retina, at the level of the retinal pigment epithelium, while after 5 days they were observed throughout the retinal thickness. These observations demonstrate that MNP-OCT may be used as an OCT intraocular delivery system that may ensure OCT localization to the retina and enhanced OCT bioactivity. Further studies will be necessary to determine the OCT release rate in the retina and the persistence of drug effects in the long period.

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Neuroprotective Peptides in Retinal Disease

Cited by 25 publications

References 260 publications

Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

A Ketogenic & Low-Protein Diet Slows Retinal Degeneration in rd10 Mice

Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy

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