Dataset Information

LIF, a mitogen for choroidal endothelial cells, protects the choriocapillaris: implications for prevention of geographic atrophy.

ABSTRACT: In the course of our studies aiming to discover vascular bed-specific endothelial cell (EC) mitogens, we identified leukemia inhibitory factor (LIF) as a mitogen for bovine choroidal EC (BCE), although LIF has been mainly characterized as an EC growth inhibitor and an anti-angiogenic molecule. LIF stimulated growth of BCE while it inhibited, as previously reported, bovine aortic EC (BAE) growth. The JAK-STAT3 pathway mediated LIF actions in both BCE and BAE cells, but a caspase-independent proapoptotic signal mediated by cathepsins was triggered in BAE but not in BCE. LIF administration directly promoted activation of STAT3 and increased blood vessel density in mouse eyes. LIF also had protective effects on the choriocapillaris in a model of oxidative retinal injury. Analysis of available single-cell transcriptomic datasets shows strong expression of the specific LIF receptor in mouse and human choroidal EC. Our data suggest that LIF administration may be an innovative approach to prevent atrophy associated with AMD, through protection of the choriocapillaris.

SUBMITTER: Li P

PROVIDER: S-EPMC8749470 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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LIF, a mitogen for choroidal endothelial cells, protects the choriocapillaris: implications for prevention of geographic atrophy.

Li Pin P Li Qin Q Biswas Nilima N Xin Hong H Diemer Tanja T Liu Lixian L Perez Gutierrez Lorena L Paternostro Giovanni G Piermarocchi Carlo C Domanskyi Sergii S Wang Ruikang K RK Ferrara Napoleone N

EMBO molecular medicine 20211115 1

In the course of our studies aiming to discover vascular bed-specific endothelial cell (EC) mitogens, we identified leukemia inhibitory factor (LIF) as a mitogen for bovine choroidal EC (BCE), although LIF has been mainly characterized as an EC growth inhibitor and an anti-angiogenic molecule. LIF stimulated growth of BCE while it inhibited, as previously reported, bovine aortic EC (BAE) growth. The JAK-STAT3 pathway mediated LIF actions in both BCE and BAE cells, but a caspase-independent proap ...[more]

PMID: 34779136

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Project description:PurposeTo evaluate the correlation between the choriocapillaris (CC) flow alterations around geographic atrophy (GA) and the GA yearly growth rate (yGR) in patients with dry age-related macular degeneration (AMD).MethodsWe retrospectively reviewed and analyzed spectral domain optical coherence tomography (SD-OCT) and SD-OCT angiography images of consecutive patients with GA acquired using the Cirrus OCT at the Doheny Eye Centers between 2015 and 2017. All eligible patients had one 6 x 6 mm OCTA scan acquired during the first visit (considered as baseline) and two fovea-centered 512 x 128 macular cubes (6 x 6 mm) acquired at baseline and after a minimum of 12 months.Main outcome measuresThe fundus images from the OCT volumes were used to manually delineate the GA area and calculate the yGR after square root transformation. The en-face angiogram at the level of the CC was analyzed for the percentage of flow voids (FV) outside the atrophic lesion (FVOUT) and in the para- and peri-atrophy regions (FV500 and FV1000 respectively; two concentric 500 μm wide rings around the atrophy edge). These values, together with the difference between FV500 and FV1000 (ΔFV), were then correlated with the corresponding yGR.ResultsThirty-three eyes of 23 patients were eligible for the analysis. The mean yGR was 0.23 ± 0.17 mm/years. At baseline, the mean FVOUT was 41.86 ± 2.71%, while FV500 and FV1000 were 46.4 ± 4.17% and 42.51 ± 2.65% respectively. The mean ΔFV was 3.89 ± 2.6%. While in the univariable analysis, the yGR was significantly associated with FV500 and with ΔFV (both p < 0.001), in multivariable model the association remained significant only with ΔFV (p < 0.001).ConclusionsOur study reports a correlation between the CC flow impairment around the atrophic lesions and their yGR in patients with GA. If replicated in future longitudinal studies, the choriocapillaris FV in the para-and peri-atrophy regions may prove to be useful parameters for evaluating the prognosis of these eyes.

Project description:PurposeTo analyze the characteristics of the choriocapillaris and the choroid in patients with Alport syndrome (AS) and investigate their clinical and demographic associations.MethodsMulticenter, cross-sectional study. Forty-two eyes with AS were consecutively enrolled. A cohort of 33 healthy eyes was included as controls. Demographics and medical history were collected for each participant. Each eye underwent 3 × 3 swept-source optical coherence tomography angiography (PLEX Elite 9000 2.0; Carl Zeiss Meditec, Dublin, CA, USA) and spectral-domain OCT (Spectralis HRA2; Heidelberg Engineering, Heidelberg, Germany). Choriocapillaris flow deficit (FD) number, mean FD size, total FD area, FD density, subfoveal choroidal thickness (CT), total CT, and choroidal vascularity index (CVI) were compared between AS and control eyes. Factors associated with the FD density and the CVI in AS were explored with multivariable linear mixed models.ResultsThere was high intragroup variability in choriocapillaris and choroidal measurements in patients with AS. Choriocapillaris FD in patients with AS were more numerous compared to controls (P = 0.02). FD density in eyes with AS increased with older age (estimate = 0.31% for each year; 95% confidence interval [CI], 0.06-0.57; P = 0.02) and was higher in patients with a history of kidney transplant (estimate = 9.66% in case of positive history; 95% CI, 3.52-15.8; P = 0.006). The CVI was lower in eyes with dot maculopathy (estimate = -3.30% if present; 95% CI, -6.38 to -0.21; P = 0.04) and anterior lenticonus (estimate = -6.50% if present; 95% CI, -10.99 to -2.00; P = 0.006).ConclusionsPatients with AS with kidney involvement requiring transplant may present with more severe choriocapillaris impairment. Lower choroidal vascularity was found in the presence of other ocular structural abnormalities.Translational relevanceAn increased load of choriocapillaris flow deficits on optical coherence tomography angiography was found in patients with Alport syndrome who also had severe kidney disease requiring transplant.

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Dataset Information

LIF, a mitogen for choroidal endothelial cells, protects the choriocapillaris: implications for prevention of geographic atrophy.

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LIF, a mitogen for choroidal endothelial cells, protects the choriocapillaris: implications for prevention of geographic atrophy.

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