fibrin and Wet-Macular-Degeneration

Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. 'Wet' AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our 'activated' BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research.

Topics: Amino Acids; Angiogenesis Inhibitors; Choroidal Neovascularization; Endothelial Cells; Fibrin; Humans; Interleukins; Transcriptome; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Wet Macular Degeneration

We aimed to study the retinal morphological findings associated with exudative age-related macular degeneration (AMD) and their association with visual prognosis.. We retrospectively reviewed the medical records of 96 consecutive patients (96 eyes) with exudative AMD. Retinal structural changes were examined using optical coherence tomography (OCT).. Initial OCT examination showed cystoid macular edema in 18 eyes (18.8%), fibrin exudate in 56 eyes (58.3%), and hyperreflective foci within the neurosensory retina in 78 eyes (81.3%). Upon initial examination, an external limiting membrane (ELM) line was detected under the fovea in 64 eyes (66.7%). Using Pearson’s correlation analyses, final visual acuity (VA) was correlated with initial VA (r = 0.61, p < 0.001), age (r = 0.34, p < 0.001), initial total foveal thickness (r = 0.41, p < 0.001), presence of hyperreflective foci (r = 0.40, p < 0.001), and detection of a foveal ELM line (r = 0.55, p < 0.001). After multiple regression analysis, final VA correlated with initial VA (r = 0.48, p < 0.001), initial presence of hyperreflective foci (r = 0.23, p = 0.054), and detection of a foveal ELM line (r = 0.36, p = 0.008).. In eyes with exudative AMD, final VA was most correlated with initial VA. In addition, the initial integrity of the foveal outer retina was partially correlated with the visual prognosis. The initial ELM condition was associated with good final VA, while the initial presence of hyperreflective foci in the foveal neurosensory retina was associated with poor final VA.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Exudates and Transudates; Female; Fibrin; Fluorescein Angiography; Humans; Macular Edema; Male; Middle Aged; Photochemotherapy; Prognosis; Retina; Retrospective Studies; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration