Photobiology of lipofuscin granules in the retinal pigment epithelium cells of the eye: norm, pathology, age

Feldman, T. B.; Донцов, А. Е.; Yakovleva, M. A.; Оstrovsky, М. А.

doi:10.1007/s12551-022-00989-9

Cited by 16 publications

(5 citation statements)

References 132 publications

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“…That is, the results of the experiments allow us to conclude that the process of photodamage is also characterized by a prolonged effect that occurs as a result of the launch of the intracellular mechanism, leading to an increase in the content of intracellular ROS level. It should be noted that the mechanisms of retina and RPE photodamage have been studied quite well [43,44]. However, our work presents the results of the effects of visible light exposure after 4.5 months (long-term effect).…”

Section: Discussionmentioning

confidence: 93%

Short-Term and Long-Term Effects after Exposure to Ionizing Radiation and Visible Light on Retina and Retinal Pigment Epithelium of Mouse Eye

Feldman,

Yakovleva,

Utina

et al. 2023

IJMS

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A comparative in vivo study of the effects of ionizing radiation (accelerated protons) and visible light (400–700 nm) on the retina and retinal pigment epithelium (RPE) of the mouse eye was carried out. Using the methods of fluorescence spectroscopy and high-performance liquid chromatography (HPLC), we analyzed the relative composition of retinoids in chloroform extracts obtained from the retinas and RPEs immediately after exposure of animals to various types of radiation and 4.5 months after they were exposed and maintained under standard conditions throughout the period. The fluorescent properties of chloroform extracts were shown to change upon exposure to various types of radiation. This fact indicates the accumulation of retinoid oxidation and degradation products in the retina and RPE. The data from fluorescence and HPLC analyses of retinoids indicate that when exposed to ionizing radiation, retinoid oxidation processes similar to photooxidation occur. Both ionizing radiation and high-intensity visible light have been shown to be characterized by long-term effects. The action of any type of radiation is assumed to activate the mechanism of enhanced reactive oxygen species production, resulting in a long-term damaging effect.

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Section: Discussionmentioning

confidence: 93%

Short-Term and Long-Term Effects after Exposure to Ionizing Radiation and Visible Light on Retina and Retinal Pigment Epithelium of Mouse Eye

Feldman,

Yakovleva,

Utina

et al. 2023

IJMS

Self Cite

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“…Studies suggest that the distribution of these substances may be related to the type of PR present in these regions [39]. Early stages of AMD are marked by degenerative changes in the RPE-photoreceptor complex, presenting as macular areas with variable pigmentation (hypo-or hyperpigmentations) [42,43]. Lipofuscin is considered to represent accumulations of undigested cellular materials arising from phagocytosis and autophagy processes [44,45].…”

Section: Lipofuscin Accumulation In Amd Pathogenesismentioning

confidence: 99%

“…Lipofuscin found in RPE cells is mainly derived from the chemically modified residues of incompletely digested PR outer segments. It is a heterogeneous material composed of a mixture of peroxidized lipids, phospholipids, and different fluorescent compounds, forming endocytoplasmic granules under both physiological conditions and pathological situations [42,46,47]. Autofluorescence of the retina primary results from the lipofuscin present within RPE granules.…”

Section: Lipofuscin Accumulation In Amd Pathogenesismentioning

confidence: 99%

Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers

Iliescu,

Ghita,

Ilie

et al. 2024

Diagnostics

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The imagistic evaluation of non-neovascular age-related macular degeneration (AMD) is crucial for diagnosis, monitoring progression, and guiding management of the disease. Dry AMD, characterized primarily by the presence of drusen and retinal pigment epithelium atrophy, requires detailed visualization of the retinal structure to assess its severity and progression. Several imaging modalities are pivotal in the evaluation of non-neovascular AMD, including optical coherence tomography, fundus autofluorescence, or color fundus photography. In the context of emerging therapies for geographic atrophy, like pegcetacoplan, it is critical to establish the baseline status of the disease, monitor the development and expansion of geographic atrophy, and to evaluate the retina’s response to potential treatments in clinical trials. The present review, while initially providing a comprehensive description of the pathophysiology involved in AMD, aims to offer an overview of the imaging modalities employed in the evaluation of non-neovascular AMD. Special emphasis is placed on the assessment of progression biomarkers as discerned through optical coherence tomography. As the landscape of AMD treatment continues to evolve, advanced imaging techniques will remain at the forefront, enabling clinicians to offer the most effective and tailored treatments to their patients.

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“…Clinical and histopathological studies have also shown that the degeneration of the PRCs in AMD patients is triggered by abnormalities in the RPE cells (Holz et al., 2007; Schmitz‐Valckenberg et al., 2009; Young, 1987). It has been shown that an excessive accumulation of lipofuscin may contribute to the death of RPE cells in dry AMD (Dorey et al., 1989; Feldman et al., 2022; Holz et al., 1999). Bis‐retinoid N‐retinyl‐N‐retinylidene ethanolamine (A2E), a byproduct of the visual cycle and well‐known component of RPE lipofuscin (Sparrow et al., 2003), was demonstrated to induce apoptosis (Sparrow & Cai, 2001; Suter et al., 2000), inhibit the lysosomal transporter (Bergmann et al., 2004), disrupt mitochondrial function (Vives‐Bauza et al., 2008), activate complement components (Zhou et al., 2006) and evoke oxidative damage in cultured RPE cells (Dontsov et al., 2009; Rózanowska et al., 1995; Sparrow et al., 2002).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial damage and clearance in retinal pigment epithelial cells

Gurubaran

2024

Acta Ophthalmologica

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Age‐related macular degeneration (AMD) is a devastating eye disease that causes permanent vision loss in the central part of the retina, known as the macula. Patients with such severe visual loss face a reduced quality of life and are at a 1.5 times greater risk of death compared to the general population. Currently, there is no cure for or effective treatment for dry AMD. There are several mechanisms thought to underlie the disease, for example, ageing‐associated chronic oxidative stress, mitochondrial damage, harmful protein aggregation and inflammation. As a way of gaining a better understanding of the molecular mechanisms behind AMD and thus developing new therapies, we have created a peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha and nuclear factor erythroid 2‐related factor 2 (PGC1α/NFE2L2) double‐knockout (dKO) mouse model that mimics many of the clinical features of dry AMD, including elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen‐like structures in retinal pigment epithelial cells (RPE). In addition, a human RPE cell‐based model was established to examine the impact of non‐functional intracellular clearance systems on inflammasome activation. In this study, we found that there was a disturbance in the autolysosomal machinery responsible for clearing mitochondria in the RPE cells of one‐year‐old PGC1α/NFE2L2‐deficient mice. The confocal immunohistochemical analysis revealed an increase in autophagosome marker microtubule‐associated proteins 1A/1B light chain 3B (LC3B) as well as multiple mitophagy markers such as PTE‐induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN), along with signs of damaged mitochondria. However, no increase in autolysosome formation was detected, nor was there a colocalization of the lysosomal marker LAMP2 or the mitochondrial marker, ATP synthase β. There was an upregulation of late autolysosomal fusion Ras‐related protein (Rab7) in the perinuclear space of RPE cells, together with autofluorescent aggregates. Additionally, we observed an increase in the numbers of Toll‐like receptors 3 and 9, while those of NOD‐like receptor 3 were decreased in PGC1α/NFE2L2 dKO retinal specimens compared to wild‐type animals. There was a trend towards increased complement component C5a and increased involvement of the serine protease enzyme, thrombin, in enhancing the terminal pathway producing C5a, independent of C3. The levels of primary acute phase C‐reactive protein and receptor for advanced glycation end products were also increased in the PGC1α/NFE2L2 dKO retina. Furthermore, selective proteasome inhibition with epoxomicin promoted both nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondrial‐mediated oxidative stress, leading to the release of mitochondrial DNA to the cytosol, resulting in potassium efflux‐dependent activation of the absent in melanoma 2 (AIM2) inflammasome and the subsequent secretion of interleukin‐1β in ARPE‐19 cells. In conclusion, the data suggest that there is at least a relative decrease in mitophagy, increases in the amounts of C5 and thrombin and decreased C3 levels in this dry AMD‐like model. Moreover, selective proteasome inhibition evoked mitochondrial damage and AIM2 inflammasome activation in ARPE‐19 cells.

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Photobiology of lipofuscin granules in the retinal pigment epithelium cells of the eye: norm, pathology, age

Cited by 16 publications

References 132 publications

Short-Term and Long-Term Effects after Exposure to Ionizing Radiation and Visible Light on Retina and Retinal Pigment Epithelium of Mouse Eye

Short-Term and Long-Term Effects after Exposure to Ionizing Radiation and Visible Light on Retina and Retinal Pigment Epithelium of Mouse Eye

Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers

Mitochondrial damage and clearance in retinal pigment epithelial cells

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