Melatonin protects retinal tissue damage in streptozotocin-induced aged rats

Atacak, Adem; Baltaci, Saltuk Bugra; Akgun-Unal, Nilufer; Moğulkoç, Rasim; Baltacı, Abdülkerim Kasım

doi:10.1016/j.archger.2023.105035

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…MLT (N-acetyl-5-methoxytryptamine) is an indoleamine hormone mainly produced and secreted by the pineal gland and is widely known as a regulator of circadian rhythms [ 32 ]. Recently, increasing evidence has shown that MLT has diverse biological functions, including antioxidant [ 33 , 34 , 35 , 36 ], anti-inflammatory [ 37 , 38 , 39 ], anti-apoptosis [ 40 , 41 ] and immunomodulation [ 42 , 43 , 44 ]. Our previous study has discovered that MLT could promote proliferation, induce autophagy, and suppress apoptosis on annulus fibrosus cells, implying a role of melatonin in alleviating IDD.…”

Section: Discussionmentioning

confidence: 99%

Medical Prospect of Melatonin in the Intervertebral Disc Degeneration through Inhibiting M1-Type Macrophage Polarization via SIRT1/Notch Signaling Pathway

et al. 2023

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The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate Mφ polarization and the inflammatory reaction of Mφs with or without MLT were detected. Conditioned medium (CM) collected from these activated Mφs with or without MLT treatment were further used to incubate NP cells. The oxidative stress, inflammation and extracellular matrix (ECM) metabolism in NP cells were determined. Then, the changes in SIRT1/Notch signaling were detected. The agonist (SRT1720) and inhibitor (EX527) of SIRT1 were used to further explore the association among MLT. The interaction between SIRT1 and NICD was detected by immunoprecipitation (IP). Finally, puncture-induced rat IDD models were established and IDD degrees were clarified by X-ray, MRI, H&E staining and immunofluorescence (IF). The results of flow cytometry and inflammation detection indicated that LPS could induce M1-type Mφ polarization with pro-inflammatory properties. MLT significantly inhibited the aforementioned process and inhibited M1-type Mφ polarization, accompanied by the alleviation of inflammation. Compared with those without MLT, the levels of oxidative stress, pro-inflammatory cytokines and ECM catabolism in NP cells exposed to CM with MLT were markedly downregulated in a dose-dependent manner. The inhibition of SIRT1 and the enhancement of Notch were observed in activated Mφs and they can be reversed after MLT treatment. This prediction was further confirmed by using the SRT1720 and EX527 to activate or inhibit the signaling. The interaction between SIRT1 and NICD was verified by IP. In vivo study, the results of MRI, Pfirrmann grade scores and H&E staining demonstrated the degree of disc degeneration was significantly lower in the MLT-treated groups when compared with the IDD control group. The IF data showed M1-type Mφ polarization decreased after MLT treatment. MLT could inhibit M1-type Mφ polarization and ameliorate the NP cell injury caused by inflammation in vitro and vivo, which is of great significance for the remission of IDD. The SIRT1/Notch signaling pathway is a promising target for MLT to mediate Mφ polarization.

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Section: Discussionmentioning

confidence: 99%

Medical Prospect of Melatonin in the Intervertebral Disc Degeneration through Inhibiting M1-Type Macrophage Polarization via SIRT1/Notch Signaling Pathway

et al. 2023

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“…MEL supplementation demonstrated a protective effect on the retina in an elderly diabetic rat model. The protective effect of MEL supplementation occurs by increasing both retinal antioxidant activity and retinal SIRT-1 gene expression [ 16 ]. Most treatments for ocular disorders involve the oral administration of MEL.…”

Section: Introductionmentioning

confidence: 99%

“…This formulation was subsequently selected for further characterization. The systems were always prepared by reconstituting the anhydrous pre-concentrated SNEDDS (pre-SNEDDS) mixtures with simulated tear fluid Pharmaceutics 2024, 16, 125 3 of 27 (STF,pH 7.4) to mimic the conditions post-ocular instillation. A small dilution volume, a suitable temperature, and gentle agitation were chosen to produce the nanoemulsions, which were then fully characterized from a technological point of view, focusing on the requirements for ophthalmic topical formulations.…”

Section: Introductionmentioning

confidence: 99%

Formulating Resveratrol and Melatonin Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Ocular Administration Using Design of Experiments

Zingale,

Bonaccorso,

D’Amico

et al. 2024

Pharmaceutics

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Recent studies have demonstrated that Sirtuin-1 (SIRT-1)-activating molecules exert a protective role in degenerative ocular diseases. However, these molecules hardly reach the back of the eye due to poor solubility in aqueous environments and low bioavailability after topical application on the eye’s surface. Such hindrances, combined with stability issues, call for the need for innovative delivery strategies. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for SIRT-1 delivery can represent a promising approach. The aim of the work was to design and optimize SNEDDS for the ocular delivery of two natural SIRT-1 agonists, resveratrol (RSV) and melatonin (MEL), with potential implications for treating diabetic retinopathy. Pre-formulation studies were performed by a Design of Experiment (DoE) approach to construct the ternary phase diagram. The optimization phase was carried out using Response Surface Methodology (RSM). Four types of SNEDDS consisting of different surfactants (Tween® 80, Tween® 20, Solutol® HS15, and Cremophor® EL) were optimized to achieve the best physico-chemical parameters for ocular application. Stability tests indicated that SNEDDS produced with Tween® 80 was the formulation that best preserved the stability of molecules, and so it was, therefore, selected for further technological studies. The optimized formulation was prepared with Capryol® PGMC, Tween® 80, and Transcutol® P and loaded with RSV or MEL. The SNEDDS were evaluated for other parameters, such as the mean size (found to be ˂50 nm), size homogeneity (PDI < 0.2), emulsion time (around 40 s), transparency, drug content (>90%), mucoadhesion strength, in vitro drug release, pH and osmolarity, stability to dilution, and cloud point. Finally, an in vitro evaluation was performed on a rabbit corneal epithelial cell line (SIRC) to assess their cytocompatibility. The overall results suggest that SNEDDS can be used as promising nanocarriers for the ocular drug delivery of RSV and MEL.

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Current state of knowledge on the centrifugal visual system (including the pinealo-to-retinal connection) in mammals and its hypothesized role in circadian rhythms

Vereczki,

Köves,

Csáki

2024

Explor Neurosci

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The ubiquity of circadian rhythms in living organisms has generally been accepted by researchers over the last century. Indeed, morphology and molecular biology of the circadian clock were described during the last fifty years. This main biological clock is located in the suprachiasmatic nucleus of the hypothalamus. This nucleus is connected with the retina by the retinohypothalamic tract. This way, light regulates the functioning of the biological clock and biological rhythms such as the sleep-wake cycle and other cyclic functions by releasing melatonin from the pineal body (PB) into the general circulation. Melatonin reaches the retina via the bloodstream as humoral feedback. More than a hundred years ago a reverse neuronal connection between the central nervous system and the retina was hypothesized. This so-called centrifugal visual or retinopetal system has been explored in detail in birds, but less information is available in mammals. In this work, the morphology and physiology of mammalian centrifugal visual pathways are reviewed. It is generally accepted that the centrifugal (retinopetal) fibers terminate mainly on the amacrine cells of the retina. Histaminergic fibers terminate on dopaminergic amacrine cells. Serotoninergic synapses were identified on ganglion cells. In addition, serotoninergic fibers were also associated with photoreceptor terminals. Luteinizing hormone releasing hormone fibers have been observed in birds, but not in mammalian retinas. In summary, based on the data available in the literature, it seems that the retinopetal system has a mandatory role in lower vertebrates, but a modulatory role in mammals. There is currently no adequate way to eliminate the centrifugal visual system that would better explain its true function.

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Melatonin protects retinal tissue damage in streptozotocin-induced aged rats

Cited by 4 publications

References 56 publications

Medical Prospect of Melatonin in the Intervertebral Disc Degeneration through Inhibiting M1-Type Macrophage Polarization via SIRT1/Notch Signaling Pathway

Medical Prospect of Melatonin in the Intervertebral Disc Degeneration through Inhibiting M1-Type Macrophage Polarization via SIRT1/Notch Signaling Pathway

Formulating Resveratrol and Melatonin Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Ocular Administration Using Design of Experiments

Current state of knowledge on the centrifugal visual system (including the pinealo-to-retinal connection) in mammals and its hypothesized role in circadian rhythms

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