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Cell Reports Jul 2023Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear...
Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD.
Topics: Animals; Mice; Choroidal Neovascularization; Endothelial Cells; Macular Degeneration; Proto-Oncogene Proteins c-akt; Retinal Pigment Epithelium; TOR Serine-Threonine Kinases; AlkB Homolog 5, RNA Demethylase
PubMed: 37436898
DOI: 10.1016/j.celrep.2023.112779 -
Retina (Philadelphia, Pa.) Mar 2024The aim of this literature review was to summarize novel optical coherence tomography (OCT) imaging biomarkers that have recently been described in the literature and... (Review)
Review
PURPOSE
The aim of this literature review was to summarize novel optical coherence tomography (OCT) imaging biomarkers that have recently been described in the literature and are frequently encountered clinically.
METHODS
The literature was reviewed to identify novel OCT biomarkers reported to date. A descriptive summary of all terms and representative illustrations were provided to highlight the most relevant features.
RESULTS
Thirty-seven OCT terminologies were identified. The vitreomacular interface disorder group included the four stages of epiretinal membrane, macular pseudohole, tractional lamellar hole (LH), degenerative LH, cotton ball sign, and foveal crack sign. The age-related macular degeneration group included outer retinal tubulation, multilayered pigment epithelial detachment, prechoroidal cleft, onion sign, double-layer sign, complete outer retinal atrophy, complete retinal pigment epithelium and outer retinal atrophy, and reticular pseudodrusen. The uveitic disorder group consisted of bacillary layer detachment, syphilis placoid, rain-cloud sign, and pitchfork sign. The disorders relating to the toxicity group included flying saucer sign and mitogen-activated protein kinase (MEK) inhibitor-associated retinopathy. The disorders associated with the systemic condition group included choroidal nodules and needle sign. The pachychoroid spectrum group included pachychoroid and brush border pattern. The vascular disorder group included pearl necklace sign, diffuse retinal thickening, disorganization of retinal inner layers, inner nuclear layer microcysts, hyperreflective retinal spots, paracentral acute middle maculopathy, and acute macular neuroretinopathy. The miscellaneous group included omega sign (ω), macular telangiectasia (type 2), and omega sign (Ω).
CONCLUSIONS
Thirty-seven OCT terminologies were summarized, and detailed illustrations consolidating the features of each biomarker were included. A nuanced understanding of OCT biomarkers and their clinical significance is essential because of their predictive and prognostic value.
Topics: Humans; Tomography, Optical Coherence; Epiretinal Membrane; Uveitis; Retinal Drusen; Biomarkers; Atrophy; Retrospective Studies
PubMed: 37903455
DOI: 10.1097/IAE.0000000000003974