Effects of Daily Melatonin Supplementation on Visual Loss, Circadian Rhythms, and Hepatic Oxidative Damage in a Rodent Model of Retinitis Pigmentosa

Fuentes-Broto, Lorena; Perdices, Lorena; Segura, Francisco; Orduna‐Hospital, Elvira; Insa-Sánchez, Gema; Sánchez‐Cano, Ana; Cuenca, Nicolás; Pinilla, Isabel

doi:10.3390/antiox10111853

Cited by 6 publications

(3 citation statements)

References 71 publications

(78 reference statements)

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“…In this case, their circadian rhythms would be expected to exhibit a non-24-hr pattern. A recent study has shown that melatonin supplementation decreased the rate of desynchronization of the circadian rhythm and improved visual function in P23H rats [90]. This provides a new possibility for treating RP through circadian synchronization and hence it is important to understand the changes in the circadian pattern in different models of RP to get a better understanding of the role of circadian rhythm on RP.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic remodeling of the retina in a Zebrafish model of Retinitis Pigmentosa

Santhanam

Shihabeddin

Wei

et al. 2022

Preprint

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Inherited retinal degenerative diseases such as Retinitis Pigmentosa (RP) result in progressive loss of photoreceptors until an individual is completely blind. A hallmark of these diseases is progressive structural and functional remodeling of the remaining retinal neurons as rod photoreceptors are lost. While many studies focus on regenerative or bionic therapies to restore vision, extensive remodeling of retinal cell types throughout the course of retinal degenerative diseases stands as a barrier for successful implementation of these strategies. As a window onto the molecular basis of remodeling, we have performed a comparative analysis of single-cell transcriptome data from adult Zebrafish retina of wild-type and a P23H mutant rhodopsin model of RP. In addition to providing a benchmark atlas of retinal cell type transcriptomes in the wild-type adult Zebrafish retina, we find transcriptional changes in essentially all retinal cell types in the P23H model. Increased oxidative stress is evident not only in the rods but also in cones, retinal pigmented epithelium (RPE) and to a lesser extent in amacrine and bipolar cells. Metabolic changes increasing oxidative metabolism and glycolysis are found in rods and cones, while evidence of increased activity of the mitochondrial electron transport chain is found in retinal ganglion cells (RGCs). Evidence of synaptic remodeling is found throughout the retina, with changes to increase synaptic transmission in photoreceptors and bipolar cells, increased ionotropic glutamate receptors in amacrine and ganglion cells, and dendritic and axon remodeling throughout. Surprisingly, RPE, cones and bipolar cells in the P23H retinas also have increased expression of genes involved in circadian rhythm regulation. While this model system undergoes continuous regeneration, ongoing remodeling impacts the entire retina. This comprehensive transcriptomic analysis provides a molecular road map to understand how the retina remodels in the context of chronic retinal degeneration with ongoing regeneration.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic remodeling of the retina in a Zebrafish model of Retinitis Pigmentosa

Santhanam

Shihabeddin

Wei

et al. 2022

Preprint

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“…Melatonin supplementation (in drinking water) in P23HxLE rats, a model that resembles the clinical features of heterozygous patients with RP, improved visual acuity, contrast sensitivity and retinal electrical activity [ 168 ]. It also improved circadian synchronization and increased the levels of CAT and SOD, which further reduced oxidative stress.…”

Section: Therapeutic Strategies To Reduce Oxidative Stress and Inflam...mentioning

confidence: 99%

Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications

et al. 2022

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Inherited retinal dystrophies (IRDs) are a large group of genetically and clinically heterogeneous diseases characterized by the progressive degeneration of the retina, ultimately leading to loss of visual function. Oxidative stress and inflammation play fundamental roles in the physiopathology of these diseases. Photoreceptor cell death induces an inflammatory state in the retina. The activation of several molecular pathways triggers different cellular responses to injury, including the activation of microglia to eliminate debris and recruit inflammatory cells from circulation. Therapeutical options for IRDs are currently limited, although a small number of patients have been successfully treated by gene therapy. Many other therapeutic strategies are being pursued to mitigate the deleterious effects of IRDs associated with oxidative metabolism and/or inflammation, including inhibiting reactive oxygen species’ accumulation and inflammatory responses, and blocking autophagy. Several compounds are being tested in clinical trials, generating great expectations for their implementation. The present review discusses the main death mechanisms that occur in IRDs and the latest therapies that are under investigation.

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“…One of these antioxidants is melatonin [5]. Melatonin, which is N-acetyl-5-methoxytryptamine, can be synthesized from tryptophan (an essential amino acid) and produced from (the brain) pineal gland, (eye) retina and lacrimal gland, digestive system, and other organs [6]. Melatonin has very important functions in regulating the circadian rhythm, cardiovascular function, regulating the immune system, vague retinal functions, and pancreatic function.…”

Section: Introductionmentioning

confidence: 99%

Correlation Between Serum Melatonin Level and Other Indicators With Stages of Diabetic Retinopathy

Mahmoud

Hashim

Ahmed

et al. 2022

Egyptian Journal of Clinical Ophthalmology

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Purpose: Diabetic retinopathy is considered the ghost cause of vision deterioration; it is attributed to elevated oxidative stress. Antioxidants, like melatonin, were found to be affected in diabetic retinopathy. In the present paper, we aim to explore melatonin levels in various stages of diabetic retinopathy. Method: Patients with diabetic retinopathy were recruited and divided into 3 groups (non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and advanced diabetic eye disease). One control group was recruited (diabetics without diabetic retinopathy). Each participant was subjected to full ophthalmological examination, internal medicine evaluation, fluorescein angiography F/A, as well as optical coherence tomography (OCT) to classify the stage of diabetic retinopathy. The laboratory evaluation of melatonin, bilirubin, aspartate transferase AST, alanine transferase ALT, fasting plasma glucose FBG, hemoglobin A1c HA1c, and lipid profile were done. Data were collected and analyzed. Results: Each group includes 60 participants. We found no different sex distribution in the four groups as (P value =0.77), age in the four groups was as follows 58.35±8.56, 55.77±14.43, 59.3±10.73, 60.98± 7.60 years with (P =0.06). For diabetes-associated variables like duration, fasting glucose levels, HA1c, and medications (insulin or oral hypoglycemic), we found this result; increased duration of diabetes with raised levels of FBG, HA1C, and insulin treatment were linked with severe diabetic retinopathy affection (P value <0.0001). When assessing the plasma melatonin levels, the mean melatonin levels were decreased significantly with increased severity of diabetic retinopathy (86.04 ± 2.71, 73.05 ± 6.91, 25.82 ± 2.89, 24.28 ± 2.37 pg/ml) in the studied groups NDR, NPDR, PDR and advanced diabetic retinopathy with (P-value < 0.0001). Decreased melatonin could be a risk factor for diabetic retinopathy. As regards total bilirubin, its mean values decreased significantly with increasing severity of DR (P-value < 0.0001). Conclusion: There is a relation between the levels of serum melatonin and the severity of diabetic retinopathy.

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Effects of Daily Melatonin Supplementation on Visual Loss, Circadian Rhythms, and Hepatic Oxidative Damage in a Rodent Model of Retinitis Pigmentosa

Cited by 6 publications

References 71 publications

Transcriptomic remodeling of the retina in a Zebrafish model of Retinitis Pigmentosa

Transcriptomic remodeling of the retina in a Zebrafish model of Retinitis Pigmentosa

Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications

Correlation Between Serum Melatonin Level and Other Indicators With Stages of Diabetic Retinopathy

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