Biology subjects

Lennikov, A.

Publications and source records attributed to Lennikov, A..

3 recordsLinked to original sources

bioRxiv2024

Endomucin knockout leads to delayed retinal vascular development and reduced ocular pathological neovascularization

Endomucin (EMCN), an endothelial-specific glycocalyx component highly expressed in capillary and venous endothelium, plays a critical role in regulating VEGF receptor 2 (VEGFR2) endocytosis and downstream VEGF signaling. Using the first global EMCN knockout mouse model, we investigated the effects of EMCN deficiency on retinal vascularization during development and pathological angiogenesis. We found relatively high expression of EMCN in choroidal capillaries and retinal vasculature. Emcn-/- mice exhibited delayed retinal vascularization at postnatal day 5, with fewer tip cells and reduced vessel density. Ultrastructural examination revealed disrupted and reduced fenestrations in choroidal capillary endothelium. In an oxygen-induced retinopathy model, while Emcn-/- mice showed no significant difference in avascular area compared to Emcn+/+ mice at postnatal day 12, there was a significant reduction in neovascular tufts in Emcn-/- mice at postnatal day 17. Similarly, in a laser-induced choroidal neovascularization model, Emcn-/- mice showed a significant reduction in vascular leakage and lesion size. These findings suggest that EMCN plays a critical role in both vascular development and pathological neovascularization, highlighting its potential as a target for anti-angiogenic therapies.

pathology↗

bioRxiv2019

Age-related macular degeneration-like phenotypic features develop at the early ages of Cxcr5/Nrf2 double knockout mice: An accelerated AMD model

Age-related macular degeneration (AMD) is a leading cause of blindness for older adults. The aim of this study is to develop an accelerated mouse model of AMD and characterize its phenotypic features. Cxcr5 knockout (KO) mice and Nrf2 KO mice were bred to create Cxcr5/Nrf2 double knockout (DKO) mice. AMD-like features in Cxcr5/Nrf2 DKO mice were compared with those in CXCR5 KO mice and C57BL6 wild-type (WT) controls. The assessment included fundus and optical coherence tomography (OCT) imaging, periodic acid-Schiff (PAS) and immunofluorescence staining of retinal pigment epithelium (RPE)-choroid flat mounts and sections. Stained samples were imaged with fluorescent microscopy, and Western blots were used to monitor protein expression changes. The staining of cleaved caspase-3, peanut agglutinin (PNA) lectin, and MAP2 was performed to assess the presence of retinal degeneration and cell apoptosis. Quantification with statistical analysis was performed with Graphpad software. The 2- 4-, and 6-month-old DKO mice exhibited increased hypopigmented spots on fundus and sub-RPE abnormalities on OCT as compared to the Cxcr5 KO mice, and C57BL6 WT controls. Aberrant RPE/sub-RPE depositions and increased Bruchs membrane (BM) thickness were demonstrated by PAS-stained sections. The DKO mice had strong autofluorescence (A2E) and increased RPE/sub-RPE depositions of IgG and AMD-associated proteins ({beta} amyloid, Apolipoprotein E, complement 5b-9, and B-crystallin). The protein expression of AMD-associated proteins and Transmembrane Protein 119 (TMEM119) microglia marker were upregulated at the RPE/BM/choroid complex of DKO mice. The adult DKO mice underwent accelerated retinal degeneration and cell apoptosis compared to the KO and the WT mice. Together, the data suggest that the Cxcr5/Nrf2 DKO mice develop significant AMD-like characteristics at an early age and may serve as an accelerated AMD model. Sumary StatementA new animal model is developed to mimic early AMD characteristics in adult mice

pathology↗

bioRxiv2018

Proteomics reveals ablation of placental growth factor inhibits the insulin resistance pathways in diabetic mouse retina

The underlying molecular mechanisms that placental growth factor (PlGF) mediates the early complications at non-proliferative diabetic retinopathy (DR) remain largely elusive. The objective of this study is to characterize expression profile due to PlGF ablation in the retina of diabetic mice. The quantitative label-free proteomics was carried out on retinal tissues collected from mouse strains (Akita; PlGF-/- and Akita.PlGF-/-). We have identified 3176 total proteins, and 107 were significantly different between the experimental groups, followed by gene ontology, functional pathways, and protein-protein network interaction analysis. Gnb1, Gnb2, Gnb4, Gnai2, Gnao1, Snap25, Stxbp1, Vamp2 and Gngt1 proteins are involved in insulin resistance pathways, which are down-regulated in PlGF ablation in Akita diabetics (Akita.PlGF-/- vs. Akita), up-regulation in Akita vs. C57, PlGF-/- vs. C57. Prdx6, Prdx5 (up-regulation) are known of antioxidant activity; Map2 is involved in neural protection pathways which are up-regulated in Akita.PlGF-/- vs. Akita. Our results suggest that inhibition of insulin resistance pathway and the enhancement of antioxidant defence and neural function may represent the potential mechanisms of anti-PlGF compounds in the treatment of DR.

molecular biology↗