Exudative versus Nonexudative Age-Related Macular Degeneration: Physiopathology and Treatment Options

Fernandes, Ana Rita; Zielińska, Aleksandra; Santos, Tiago dos; García, María L.; Silva, Amélia M.; Karczewski, Jacek; Souto, Eliana B.

doi:10.3390/ijms23052592

Cited by 42 publications

(52 citation statements)

References 176 publications

(196 reference statements)

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“…Early AMD culminates in aberrant RPE pigment distribution in the macula, and between the inner collagenous layer of Bruch's membrane and the RPE's basal lamina, in the retina, a variety of proteins and drusen-containing lipids are garnered. Although early AMD is typically asymptomatic, it can produce a little loss in visual acuity and function that delays the onset of night blindness [10].…”

Section: Pathophysiologymentioning

confidence: 99%

Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

Vyawahare¹,

Shinde²

2022

Cureus

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The greatest global root of irremediable amaurosis in the venerable is age-related macular degeneration (AMD), a complex eye condition. Clinically, AMD is characterized as being in an early stage to late stage and initially affects the macula, which is the center of the retina (advanced AMD). Age-related cellular and metabolic imbalance are made worse by the creation of excessive amounts of free radical species, which causes mitochondrial malfunction. As a result, in AMD-affected eyes, the deprivation of melanocytes, confection, and eventually atrophy within the retinal tissue are caused by the continued proliferation of oxidative stress caused by systemic antioxidant capacity depletion.In the urbanized, industrialized world, age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group. Although several causes and mechanisms for the dysfunction and degeneration of the retinal pigment epithelium (RPE) have previously been identified, the condition's symptoms are still not fully understood. Etiopathogenesis is still not entirely understood. As a result, the RPE fails, allowing an accumulation of aberrant misfolded proteins, due to the loss of anatomical control over oppression, altered homeostasis, dysfunctional lipid homeostasis, and failure of mitochondria.Due to the multitude of interconnected processes, numerous complicated therapy combinations will probably be the best option to deliver the best visual outcomes; these combinations will vary depending on the kind and degree of the condition being treated. Undoubtedly, this will lead to the development of customized preventative medications and, hopefully, the revelation of a potential cure. All the mechanisms involved in the etiology of AMD should be continuously probed to create covariates for other contemporaneous or future problems.

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Section: Pathophysiologymentioning

confidence: 99%

Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

Vyawahare¹,

Shinde²

2022

Cureus

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“…Age-related macular degeneration (AMD) is the most common blinding disease in elderly people in developed countries and represents the third leading cause for blinding worldwide [1,2]. AMD patients develop distorted central vision which can progress to loss of central, high acuity vision caused by a gradual degeneration of photoreceptors in the macula.…”

Section: Introductionmentioning

confidence: 99%

“…Most AMD patients (~90%) develop dry AMD or geographic atrophy which is associated with dysfunction and gradual degeneration of RPE cells, choriocapillaris, and photoreceptors. The other late form is wet or neovascular AMD, which is associated with choroidal neovascularization, vessel leakage and scarring of the retina [1,5,8]. Unfortunately, there is still no convincing treatment for dry AMD [9].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia aggravates ferroptosis in RPE cells by promoting the Fenton reaction

Henning

Blind²,

Larafa³

et al. 2022

Cell Death Dis

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Oxidative stress and hypoxia in the retinal pigment epithelium (RPE) have long been considered major risk factors in the pathophysiology of age-related macular degeneration (AMD), but systematic investigation of the interplay between these two risk factors was lacking. For this purpose, we treated a human RPE cell line (ARPE-19) with sodium iodate (SI), an oxidative stress agent, together with dimethyloxalylglycine (DMOG) which leads to stabilization of hypoxia-inducible factors (HIFs), key regulators of cellular adaptation to hypoxic conditions. We found that HIF stabilization aggravated oxidative stress-induced cell death by SI and iron-dependent ferroptosis was identified as the main cell death mechanism. Ferroptotic cell death depends on the Fenton reaction where H2O2 and iron react to generate hydroxyl radicals which trigger lipid peroxidation. Our findings clearly provide evidence for superoxide dismutase (SOD) driven H2O2 production fostering the Fenton reaction as indicated by triggered SOD activity upon DMOG + SI treatment as well as by reduced cell death levels upon SOD2 knockdown. In addition, iron transporters involved in non-transferrin-bound Fe2+ import as well as intracellular iron levels were also upregulated. Consequently, chelation of Fe2+ by 2’2-Bipyridyl completely rescued cells. Taken together, we show for the first time that HIF stabilization under oxidative stress conditions aggravates ferroptotic cell death in RPE cells. Thus, our study provides a novel link between hypoxia, oxidative stress and iron metabolism in AMD pathophysiology. Since iron accumulation and altered iron metabolism are characteristic features of AMD retinas and RPE cells, our cell culture model is suitable for high-throughput screening of new treatment approaches against AMD.

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“…Age-related macular degeneration (AMD) is a common multifactorial eye disease of the central area in the ocular posterior segment, also known as macula lutea [ 1 , 2 ]. This is an essential retinal area for the vision of fine details and image resolution by capturing the greatest focus of external light stimuli [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Approaches for Age-Related Macular Degeneration

Galindo

Blanco-Llamero

Ana

et al. 2022

IJMS

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Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the nonexudative (dry form) and the exudative (wet form). Currently, there is no ideal treatment available for AMD. Recommended standard treatments are based on the use of vascular endothelial growth factor (VEGF), with the disadvantage of requiring repeated intravitreal injections which hinder patient’s compliance to the therapy. In recent years, several synthetic and natural active compounds have been proposed as innovative therapeutic strategies against this disease. There is a growing interest in the development of formulations based on nanotechnology because of its important role in the management of posterior eye segment disorders, without the use of intravitreal injections, and furthermore, with the potential to prolong drug release and thus reduce adverse effects. In the same way, 3D bioprinting constitutes an alternative to regeneration therapies for the human retina to restore its functions. The application of 3D bioprinting may change the current and future perspectives of the treatment of patients with AMD, especially those who do not respond to conventional treatment. To monitor the progress of AMD treatment and disease, retinal images are used. In this work, we revised the recent challenges encountered in the treatment of different forms of AMD, innovative nanoformulations, 3D bioprinting, and techniques to monitor the progress.

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Exudative versus Nonexudative Age-Related Macular Degeneration: Physiopathology and Treatment Options

Cited by 42 publications

References 176 publications

Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

Hypoxia aggravates ferroptosis in RPE cells by promoting the Fenton reaction

Therapeutic Approaches for Age-Related Macular Degeneration

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