As in Real Estate, Location Matters: Cellular Expression of Complement Varies Between Macular and Peripheral Regions of the Retina and Supporting Tissues

Zauhar, Randy J.; Biber, Josef; Jabri, Yassin; Kim, Mijin; Hu, Jian; Kaplan, Lew; Pfaller, Anna M.; Schäfer, Nicole; Enzmann, Volker; Schlötzer‐Schrehardt, Ursula; Straub, Tobias; Hauck, Stefanie M.; Gamlin, Paul D.; McFerrin, Michael B.; Messinger, Jeffrey D.; Strang, Christianne E.; Curcio, Christine A.; Dana, Nicholas; Pauly, Diana; Grosche, Antje; Li, Mingyao; Stambolian, Dwight

doi:10.3389/fimmu.2022.895519

Cited by 21 publications

(26 citation statements)

References 98 publications

(112 reference statements)

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“…A combination of transcriptomics and proteomics was employed by Zauhar et al [ 58 ], to dissect the role of multiple retinal and choroidal cell types (Müller glia, neurons and RPE/choroid) in determining complement homeostasis. The results indicated that this process has a key role in the involvement of RPE cells in progression to late AMD.…”

Section: Resultsmentioning

confidence: 99%

Recent Advances in Proteomics-Based Approaches to Studying Age-Related Macular Degeneration: A Systematic Review

García-Quintanilla

Rodríguez-Martínez²,

Bandín-Vilar

et al. 2022

IJMS

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Age-related macular degeneration (AMD) is a common ocular disease characterized by degeneration of the central area of the retina in the elderly population. Progression and response to treatment are influenced by genetic and non-genetic factors. Proteomics is a powerful tool to study, at the molecular level, the mechanisms underlying the progression of the disease, to identify new therapeutic targets and to establish biomarkers to monitor progression and treatment effectiveness. In this work, we systematically review the use of proteomics-based approaches for the study of the molecular mechanisms underlying the development of AMD, as well as the progression of the disease and on-treatment patient monitoring. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guidelines were followed. Proteomic approaches have identified key players in the onset of the disease, such as complement components and proteins involved in lipid metabolism and oxidative stress, but also in the progression to advanced stages, including factors related to extracellular matrix integrity and angiogenesis. Although anti-vascular endothelial growth factor (anti-VEGF)-based therapy has been crucial in the treatment of neovascular AMD, it is necessary to deepen our understanding of the underlying disease mechanisms to move forward to next-generation therapies for later-stage forms of this multifactorial disease.

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Section: Resultsmentioning

confidence: 99%

Recent Advances in Proteomics-Based Approaches to Studying Age-Related Macular Degeneration: A Systematic Review

García-Quintanilla

Rodríguez-Martínez²,

Bandín-Vilar

et al. 2022

IJMS

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“…When treating the RPE cell line Acute Retinal Pigment Epithelium‐19 (ARPE‐19) with WT C9 and the p.Pro167Ser variant, however, no differences were detected 65 . In this context, it should be noted that RPE do not secrete C9, but show high concentrations of the C9 inhibitor CD59 50,51 . However, as discussed in the following, multiple studies showed susceptibility of the choroid to C5b‐9 deposition.…”

Section: The Alternative Pathway In Amdmentioning

confidence: 97%

Age‐related macular degeneration: A disease of extracellular complement amplification

Jong

Tang

Clark

2022

Immunological Reviews

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Western world, with more than 10% of individuals above 70 years affected in Europe. 1 Due to the increasing age of the general population, the number of AMD patients is expected to increase in the coming years, posing a major burden for healthcare systems. 2 The affected tissue in AMD is the macula, which is the part of the retina involved in central vision (Figure 1). The retina is a layered structure consisting of the following layers listed from anterior to posterior: ganglion cell layer (ganglion cells), inner plexiform layer (neuronal synapses connecting bipolar cells, amacrine cells, and retinal ganglion cells), inner nuclear layer (nuclei of bipolar, amacrine, horizontal, and Müller cells), outer plexiform layer (neuronal synapses connecting from photoreceptor cells, horizontal cells, and bipolar cells), and the outer nuclear layer (photoreceptor cell nuclei). 3 Adjacent to the photoreceptor outer segments, is the retinal pigment epithelium (RPE), which supports photoreceptor function by phagocytosing outer segments, providing growth factors and nutrients. Additionally, the RPE forms together with its underlying extracellular matrix (ECM) called Bruch's membrane (BrM), the outer blood/retinal barrier. 4 AMD patients often experience blurred or shadowed central vision as first symptoms. Characteristics for the clinical diagnosis

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“…This study involved 11 samples of human macula from three dataset series (GSE137537, GSE188280, and GSE203499) (Menon et al, 2019;Zauhar et al, 2022), including retinas from four AMD patients and seven healthy controls without degeneration. The details of each donor were listed in Table 1.…”

Section: Human Samples Of Retinal Macula For Analysismentioning

confidence: 99%

Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula

Liu

Zhong

et al. 2022

Front. Neurosci.

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Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells.

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As in Real Estate, Location Matters: Cellular Expression of Complement Varies Between Macular and Peripheral Regions of the Retina and Supporting Tissues

Cited by 21 publications

References 98 publications

Recent Advances in Proteomics-Based Approaches to Studying Age-Related Macular Degeneration: A Systematic Review

Recent Advances in Proteomics-Based Approaches to Studying Age-Related Macular Degeneration: A Systematic Review

Age‐related macular degeneration: A disease of extracellular complement amplification

Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula

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