Neuroprotective Effects of Voluntary Exercise in an Inherited Retinal Degeneration Mouse Model

Hanif, Adam M.; Lawson, Eric C.; Prunty, Megan; Gogniat, Marissa A.; Aung, Moe H.; Chakraborty, Ranjay; Boatright, Jeffrey H; Pardue, Machelle T.

doi:10.1167/iovs.15-16792

Cited by 43 publications

(55 citation statements)

References 46 publications

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“…Voluntary exercise using running wheel for 6 weeks was also suggested to protect photoreceptor in the retinitis pigmentosa model in mice (Hanif et al. ). The underlying mechanisms of how exercise induces neuroprotection include upregulating neurotrophin expression, such as brain‐derived neurotrophic factor (BDNF), enhancing mitochondrial function and reducing inflammation.…”

Section: Neuroprotection Of Physical Exercise In Glaucomamentioning

confidence: 99%

“…After 4 weeks of exercise (preconditioning of exercise for 2 weeks and additional 2 weeks of exercise after light exposure) at intensity of 10 metres/min, at a frequency of 5 days/ week, 60 min/day, was found to be effective in preserving function and count of photoreceptors in lightinduced retinal degenerative models in mice (Lawson et al 2014;Chrenek et al 2016). Voluntary exercise using running wheel for 6 weeks was also suggested to protect photoreceptor in the retinitis pigmentosa model in mice (Hanif et al 2015). The underlying mechanisms of how exercise induces neuroprotection include upregulating neurotrophin expression, such as brain-derived neurotrophic factor (BDNF), enhancing mitochondrial function and reducing inflammation.…”

Section: Neuroprotection Of Physical Exercise In Glaucomamentioning

confidence: 99%

See 1 more Smart Citation

Physical exercise and glaucoma: a review on the roles of physical exercise on intraocular pressure control, ocular blood flow regulation, neuroprotection and glaucoma‐related mental health

Zhu

Lai

Choy

et al. 2018

Acta Ophthalmologica

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The benefits of physical exercise on health and well-being have been studied in a wide range of systemic and ocular diseases, including glaucoma, a progressive optic neuropathy characterized by accelerated apoptosis of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) and insufficient ocular perfusion have been postulated to be the two main theories in glaucoma development and progression. The effects of exercise in these two aspects have been demonstrated by numerous researches. A review in 2009 focusing on these two theories concluded that exercise results in transient IOP reduction but an inconsistent elevation in ocular perfusion. However, the majority of the studies had been conducted in healthy subjects. Over the past decade, technological advancement has brought forth new and more detailed evidence regarding the effects of exercise. Moreover, the neuroprotective effect of exercise by upregulation of neurotrophin and enhancement of mitochondrial function has been a focus of interest. Apart from visual impairment, the mental health issues in patients with glaucoma, which include anxiety and depression, should also be addressed. In this review, we mainly focus on publications from the recent years, so as to provide a comprehensive review on the impact of physical exercise on IOP, ocular perfusion, neuroprotection and mental health in patients with glaucoma.

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Section: Neuroprotection Of Physical Exercise In Glaucomamentioning

confidence: 99%

Section: Neuroprotection Of Physical Exercise In Glaucomamentioning

confidence: 99%

Physical exercise and glaucoma: a review on the roles of physical exercise on intraocular pressure control, ocular blood flow regulation, neuroprotection and glaucoma‐related mental health

Zhu

Lai

Choy

et al. 2018

Acta Ophthalmologica

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“…42, 46, 47, 50, 70–76 We found that retinal NR protection extends to these two arRP models (Fig 4-6), with significant increases of ERG amplitudes well after photoreceptor degeneration onset and retinal function loss in untreated cohorts. 42, 46, 47, 50, 70–74, 76 The NR-induced increase in ERG mean amplitudes in IRBP KO mice, though significant (Fig. 4), was modest most likely because retinal function has not yet declined dramatically at this early stage in the degeneration.…”

Section: Discussionmentioning

confidence: 67%

“…rd10 mice on a C57BL/6J background 46, 47 were obtained from Jackson Laboratories (Bar Harbor, Maine). In the rd10 retina, rod cell death begins at about P15, and by P25 almost all of the rod photoreceptors have been lost.…”

Section: Methodsmentioning

confidence: 99%

Systemic Treatment with Nicotinamide Riboside is Protective in Three Mouse Models of Retinal Degeneration

Zhang

Henneman

Girardot

et al. 2019

Preprint

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24Purpose: The retina is highly metabolically active, suggesting that metabolic 25 dysfunction could underlie many retinal degenerative diseases. Nicotinamide 26 adenine dinucleotide (NAD + ) is a cofactor and a co-substrate in several cellular 27 energetic metabolic pathways. Maintaining NAD + levels may be therapeutic in 28 retinal disease since retinal NAD + levels decline with age and during retinal 29 damage or degeneration. The purpose of this study was to investigate whether 30 systemic treatment with nicotinamide riboside (NR), a NAD + precursor, is 31 protective in disparate models of retinal damage or degeneration. 32 33 Methods: Three mouse models of retinal degeneration were tested: an albino 34 mouse model of light-induced retinal degeneration (LIRD) and two models of 35 retinitis pigmentosa (RP), including a mouse line deficient in interphotoreceptor 36 binding protein (IRBP) gene expression (IRBP KO), and a naturally-occuring 37 cGMP phosphodiesterase 6b mutant mouse model of RP (the Pde6b rd10 mouse). 38 Mice were intraperitoneally (IP) injected with PBS or NR at various times relative 39 to damage or degeneration onset. One to two weeks later, retinal function was 40 assessed by electroretinograms (ERGs) and retinal morphology was assessed 41 by optical coherence tomography (OCT). Afterwards, retina sections were H&E 42 stained for morphological analysis or by terminal deoxynucleiotidyl transferase 43 dUTP nick and labeling (TUNEL). Retinal NAD + /NADH levels were enzymatically 44 assayed. 45 46 3 Results: The retinal degeneration models exhibited significantly suppressed 47 retinal function, and where examined, severely disrupted photoreceptor cell layer 48 and significantly decreased numbers of nuclei and increased accumulation of 49 DNA breaks as measured by TUNEL-labeled cells in the outer nuclear layer 50 (ONL). These effects were prevented by various NR treatment regimens. IP 51 treatment with NR also resulted in increased levels of NAD + in retina. 52 53 Conclusions: This is the first study to report protective effects of NR treatment in 54 mouse models of retinal degeneration. The positive outcomes in several models, 55 coupled with human tolerance to NR dosing, suggest that maintaining retinal 56 NAD + via systemic NR treatment should be further explored for clinical relevance. 57 58 59 60 61 62 63 64 65 66 67 68 0.00039 0.00374 0.058 0.961 25.3 Flash intensity (cd s/m 2 ) Flash intensity (cd s/m 2 ) Flash intensity (cd*s/m 2 ) * * * * 0.00039 0.00374 0.058 0.961 25.3 Flash intensity (cd s/m 2 ) Flash intensity (cd s/m 2 )

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“…Regular general physical exercise is not only a part of healthy life style, but also a rehabilitation strategy showing neuroprotective effects in numerous diseases. Recently, exercise has been proven to be neuroprotective in animal models of retinal degeneration [85][86][87]. Wild-type BALB/c mice were forced to exercise for 5 days/ week for 2 weeks before being exposed to bright light.…”

Section: Studies In Animal Modelsmentioning

confidence: 99%

Protecting the Aging Retina

Shen¹,

Lo²

2019

Neuroprotection

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Aging retina, notably the aging macula, is prone to develop degenerative diseases, such as age-related macular degeneration (AMD), the leading cause of visual loss in individuals aged 65 or above in developed countries. However, current treatments are very limited. Since degeneration, dysfunction, and death of retinal neurons are demonstrated in the pathogenesis of AMD, neuroprotective strategies could serve as a possible way to treat AMD. In this chapter, we will briefly introduce risk factors, pathophysiology, affected neurons, classification, clinical manifestation, and current treatments of AMD. Finally, neuroprotection in both AMD animal models and patients will be discussed. Neuroprotection 2 Anatomy and function of the retinaThe eye is composed of three layers, which are the inner retina layer, middle vascular choroid layer, and outer fibrous sclera layer, respectively. Retina, the innermost layer of the eye, consists of two parts: the inner transparent neurosensory retina and outer pigmented epithelial layer-the retinal pigment epithelium (RPE). There is a potential space between neural retina and RPE, called subretinal space. In the neural retina, the neural cell bodies are situated in three layers (Figure 1), including the outer nuclear layer (ONL) occupied with nuclei of photoreceptors; the inner nuclear layer (INL) filled with nuclei of horizontal, bipolar, and most of the amacrine cells; as well as ganglion cell layer (GCL) containing nuclei of retinal ganglion cells and the rest of displaced amacrine cells. Additionally, axons and dendrites of these retinal neurons constitute two synaptic layers: the inner plexiform layer (IPL) and outer plexiform layer (OPL) [8]. The RPE cells form a continuous polarized cell monolayer with its apical surface adjacent to the outer segment apices of the photoreceptors and its basal aspect lying on supportive substrate Bruch's membrane.Retinal neurons are mainly distributed in three layers: ONL with nuclei of photoreceptors; INL with nuclei of horizontal, bipolar, and most of the amacrine cells; and GCL with nuclei of retinal ganglion cells and the rest of displaced amacrine cells. Additionally, axons and dendrites of these retinal neurons constitute two synaptic layers, including IPL and OPL [8].Photoreceptors are divided into two types: rods, which are dominated in the peripheral retina and responsible for dim light vision and detecting movement and contrast, and cones, which are dominated in the macula, especially the fovea (only cones), and are responsible for bright light vision and sensing color vision Figure 1. Retinal layers of the human eye.Protecting the Aging Retina DOI: http://dx.doi.org/10.5772/intechopen.82330 and resolution. Outer segments of the photoreceptor are generated by the cell body, and the distal parts of outer segments are phagocytosed by RPE every day. There are abundant mitochondria in inner segments to supply energy for these cells with high metabolic rate. Bruch's membrane, where the RPE cells are tightly attached, consists of five la...

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Neuroprotective Effects of Voluntary Exercise in an Inherited Retinal Degeneration Mouse Model

Cited by 43 publications

References 46 publications

Physical exercise and glaucoma: a review on the roles of physical exercise on intraocular pressure control, ocular blood flow regulation, neuroprotection and glaucoma‐related mental health

Physical exercise and glaucoma: a review on the roles of physical exercise on intraocular pressure control, ocular blood flow regulation, neuroprotection and glaucoma‐related mental health

Systemic Treatment with Nicotinamide Riboside is Protective in Three Mouse Models of Retinal Degeneration

Protecting the Aging Retina

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