Apoptosis of photoreceptor cells in ornithine-induced retinopathy

Maeda, Hidemi; Ogata, Nahoko; Yi, Xianhua; Takeuchi, Masamitsu; Ohkuma, H; Uyama, M

doi:10.1007/s004170050066

Cited by 15 publications

(12 citation statements)

References 22 publications

(20 reference statements)

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“…The pathological changes mentioned above were consistent with the functional research exhibiting that scotopic sensitivity decreased more than photopic sensitivity in cases with AMD [51]. Maeda and colleagues revealed the apoptosis of photoreceptors after RPE damage caused by intravitreal injection of ornithine in rats, indicating the important role of RPE cells in maintaining photoreceptor integrity [52]. In AMD patients, apoptotic photoreceptors and RPE cells (TUNEL positive) were observed as well.…”

Section: Affected Neuronssupporting

confidence: 79%

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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Section: Affected Neuronssupporting

confidence: 79%

Protecting the Aging Retina

Shen¹,

Lo²

2019

Neuroprotection

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“…Dunaief also suggested the Fas/Fas ligand system may be involved in photoreceptor apoptosis in AMD (Dunaief et al, 2002). Maeda et al observed that the loss of photoreceptors was directly related to loss of RPE after intravitreal ornithine-induced degeneration, suggesting the importance of RPE in photoreceptor viability (Maeda et al, 1998). In geographic atrophy, Kim et al observed that photoreceptors loss was associated with RPE loss (Kim et al, 2002a).…”

Section: 0 Basic Definitions Of Exudative and Dry Age-related Maculmentioning

confidence: 99%

Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex

Bhutto

Lutty

2012

Molecular Aspects of Medicine

823

674

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There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch’s membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85–90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10–15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex.

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“…Although the pathogenesis of AMD remains unclear, there is evidence that degeneration or dysfunction of RPE cells often occurs in the early AMD pathogenesis and can be a predictor of photoreceptor loss although in cases such as outer retinal atrophy associated with pseudodrusen, photoreceptor loss can precede RPE disease. [91][92][93][94][95]…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Retinal pigment epithelium in the pathogenesis of age‐related macular degeneration and photobiomodulation as a potential therapy?

Wood

Chidlow

et al. 2018

Clinical Exper Ophthalmology

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The retinal pigment epithelium (RPE) comprises a monolayer of cells located between the neuroretina and the choriocapillaries. The RPE serves several important functions in the eye: formation of the blood-retinal barrier, protection of the retina from oxidative stress, nutrient delivery and waste disposal, ionic homeostasis, phagocytosis of photoreceptor outer segments, synthesis and release of growth factors, reisomerization of all-trans-retinal during the visual cycle, and establishment of ocular immune privilege. Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Dysfunction of the RPE has been associated with the pathogenesis of AMD in relation to increased oxidative stress, mitochondrial destabilization and complement dysregulation. Photobiomodulation or near infrared light therapy which refers to non-invasive irradiation of tissue with light in the far-red to near-infrared light spectrum (630-1000 nm), is an intervention that specifically targets key mechanisms of RPE dysfunction that are implicated in AMD pathogenesis. The current evidence for the efficacy of photobiomodulation in AMD is poor but its safety profile and proposed mechanisms of action motivate further research as a novel therapy for AMD.

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Apoptosis of photoreceptor cells in ornithine-induced retinopathy

Cited by 15 publications

References 22 publications

Protecting the Aging Retina

Protecting the Aging Retina

Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex

Retinal pigment epithelium in the pathogenesis of age‐related macular degeneration and photobiomodulation as a potential therapy?

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