A Linkage between Angiogenesis and Inflammation in Neovascular Age-Related Macular Degeneration

Heloterä, Hanna

doi:10.3390/cells11213453

Cited by 37 publications

(29 citation statements)

References 120 publications

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“…With the increasing elderly population, visual impairment is to be anticipated 18 . Currently, cataract surgery remains as the leading eye surgeries specifically in the aging population 6,[19][20][21] .…”

Section: Discussionmentioning

confidence: 99%

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Association Between Cataract Surgery and Age-Related Macular Degeneration: A Systematic Review

Anggarini¹

2023

JARMHS

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Background: As a leading cause of visual impairment in elderly, age-related macular degeneration has an increasing global incidence annually. It’s association towards cataract surgery remains a debate. Aim: The objective of this study is to summarize and evaluate the association between cataract surgery and age-related macular degeneration. Methods: A systematic search strategy was conducted across several electronic reference databases (PubMed, Cochrane Library, ProQuest) and included articles published between 2018–2023. Duplicate publications, review articles, and incomplete articles were excluded. Results: Databases searching identified a total of 254 articles. Of these, 29 articles passed the screening process and resulted in 12 articles for full-text assessment. The 6 articles did not evaluate the outcome of interest. Hence, we found six appropriate studies included in this review. Conclusion: The results suggest that there may be an association of cataract surgery and increased risk of AMD progression and development. This association may increase according to the time of follow-up since cataract surgery. To improve medical treatment and for patients with cataract and AMD, additional research is essential to increase understanding of the disease state and its impact on AMD progression mainly prospective multicenter and RCT studies.

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Section: Discussionmentioning

confidence: 99%

“…Our review can also be a basis for the informed consent with patients and medical team before and after cataract surgery. It is also important to identify the risk factors of cataract surgery and AMD, as both share similar risk factors such as age, sex, ethnicity, and the signs of AMD before and after surgery 10,18 .…”

Section: Discussionmentioning

confidence: 99%

Association Between Cataract Surgery and Age-Related Macular Degeneration: A Systematic Review

Anggarini¹

2023

JARMHS

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“…Despite significant progress in understanding the molecular mechanisms of AMD and ongoing therapeutic clinical trials, a definitive cure for AMD is still not publicly available. Currently, the only treatment option involves the use of anti-vascular endothelial growth factor (anti-VEGF) drugs, administered through intravitreal injections, to slow the progression of wet AMD (Heloterä & Kaarniranta, 2022). Encouragingly, recent observations regarding complement inhibitors offer hope for patients suffering from GA (Goldberg et al, 2022;Khan et al, 2023;Khanani et al, 2023).…”

Section: Conc Lusionsmentioning

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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“…14 Angiogenic factors can induce retinal neovascularization, leading to inflammation, endothelial cell differentiation, and recruitment of T-cells and macrophages to the damaged site. 15,16 Angiotensin II initiates responses via G protein-coupled receptors known as AGTR2 (Angiotensin II receptor type-II), which include AT1R and AT2R. Research has shown that AT1R-induced angiogenesis can produce a significant increase in pro-inflammatory cytokines, 17 whereas AT2R was found to be antagonistically reduced angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Progression of retinal choroidal neovascularization by latent human cytomegalovirus infection and immunological signaling among neonatal patients admitted to tertiary care hospital

Roy,

Chatterjee,

Mishra

et al. 2024

Journal of Medical Virology

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Choroidal neovascularization (CNV) is a serious condition that affects the retina, causing partial or complete blindness in people of different ages. While CNV is a common occurrence in various chorioretinopathies, research on its occurrence in neonates is limited. Human cytomegalovirus (HCMV) is a significant health threat to neonates, with a strong association with retinal angiogenesis. However, there has been limited investigation into HCMV‐associated CNV progression. In this article, we extensively studied the expression of different inflammatory cytokines and chemokines during latent HCMV‐associated retinal neovascularization. Our research found that HCMV‐induced CNV progression was significantly prominent in the presence of AT2R‐dependent angiogenesis (p < 0.001), whereas in the absence of HCMV, AT1R‐dependent CCL‐5‐mediated angiogenesis was documented. We also observed significant increases in CCL‐19, CCL‐21 chemokine responses, followed by CCR‐7 chemokine receptor activation (p < 0.001) in HCMV‐induced CNV patients compared to HCMV non‐induced CNV groups. Furthermore, significant changes in predictive chemokine markers of HCMV‐induced CNV were positively correlated with HCMV viremia. These immunological alterations ultimately lead to the switching of NFκB canonical and noncanonical pathways, respectively, in HCMV‐induced neonatal CNV and HCMV non‐induced CNV. This clinical observation presents a novel hypothesis that ocular HCMV latency poses a noteworthy risk factor for the progression of retinal neovascularization through a distinctive immunological signaling pathway. The current study represents the first of its kind to report on this association, which may have significant implications for the clinical management of patients with ocular HCMV.

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A Linkage between Angiogenesis and Inflammation in Neovascular Age-Related Macular Degeneration

Cited by 37 publications

References 120 publications

Association Between Cataract Surgery and Age-Related Macular Degeneration: A Systematic Review

Association Between Cataract Surgery and Age-Related Macular Degeneration: A Systematic Review

Mitochondrial damage and clearance in retinal pigment epithelial cells

Progression of retinal choroidal neovascularization by latent human cytomegalovirus infection and immunological signaling among neonatal patients admitted to tertiary care hospital

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