Anton Lennikov

Schepens Eye Research Institute · Department of Ophthalmology

Electrical stimulation (ES) influences neural regeneration and functionality. We here investigate whether ES regulates DNA demethylation, a critical epigenetic event known to influence nerve regeneration. Retinal ganglion cells (RGCs) have long served as a standard model for central nervous system neurons, whose growth and disease development are r...

Microglia shift toward an inflammatory phenotype during aging that is thought to exacerbate age-related neurodegeneration. The molecular and cellular signals that resolve neuroinflammation post-injury are largely undefined. Here, we exploit systems genetics methods based on the extended BXD murine reference family and identify IGFBPL1 as an upstrea...

Redox homeostasis is a delicate balancing act of maintaining appropriate levels of antioxidant defense mechanisms and reactive oxidizing oxygen and nitrogen species. Any disruption of this balance leads to oxidative stress, which is a key pathogenic factor in several ocular diseases. In this review, we present the current evidence for oxidative str...

Purpose Transcorneal electrical stimulation (TcES) is increasingly applied as a therapy for preserving and improving vision in retinal neurodegenerative and ischemic disorders. However, a common complaint about TcES is its induction of eye pain and dryness in the clinic, while the mechanisms remain unknown. Method TcES or transpalpebral ES (TpES)...

Purpose: Placental growth factor (PlGF) and Angiopoietin (Ang)-1 are two proteins that are involved in the regulation of endothelial cell (EC) growth and vasculature formation. In the retina and endothelial cells, pericytes are the major source of both molecules. The purpose of this study is to examine the association of PlGF and Ang-1 with human...

Visual impairment from corneal stromal disease affects millions worldwide. We describe a cell-free engineered corneal tissue, bioengineered porcine construct, double crosslinked (BPCDX) and a minimally invasive surgical method for its implantation. In a pilot feasibility study in India and Iran (clinicaltrials.gov no. NCT04653922), we implanted BPC...

The cornea is an avascular, transparent tissue that is essential for visual function. Any disturbance to the corneal transparency will result in a severe vision loss. Due to the avascular nature, the cornea acquires most of the oxygen supply directly or indirectly from the atmosphere. Corneal tissue hypoxia has been noticed to influence the structu...

Our previous studies found that the C-X-C motif chemokine receptor 5 (CXCR5) loss leads to retinal pigment epithelium (RPE) dysfunction and AMD pathogenesis. The current study aimed to characterize the G protein-coupled receptor (GPCR) structure of CXCR5 and analyze its interactions with AMD-related risk genes. The sequence alignments, homology mod...

Tumor-infiltrating immune cells are capable of effective cancer surveillance, and their abundance is linked to better prognosis in numerous tumor types. However, in uveal melanoma (UM), extensive immune infiltrate is associated with poor survival. This study aims to decipher the role of different tumor-infiltrating cell subsets in UM in order to id...

Purpose To evaluate Nuclear Factor NF-κB (NF-κB) signaling on microglia activation, migration, and angiogenesis in laser-induced choroidal neovascularization (CNV). Methods Nine-week-old C57BL/6 male mice were randomly assigned to IMD-0354 treated or untreated groups (5 mice, 10 eyes per group). CNV was induced with a 532-nm laser. Laser spots (po...

Placental growth factor (PlGF or PGF) is a member of the VEGF (vascular endothelial growth factor) family. It plays a pathological role in inflammation, vascular permeability, and pathological angiogenesis. The molecular signaling by which PlGF mediates its effects in non-proliferative diabetic retinopathy (DR) remains elusive. This study aims to c...

To investigate the role of placental growth factor/vascular endothelial growth factor (PlGF-VEGF) heterodimers are involved in the blood-retinal barrier (BRB) breakdown and the associated mechanism, human retinal endothelial cells (HRECs) were treated with recombinant human (rh)PlGF-VEGF heterodimers and rhPlGF and studied in normal and high-glucos...

Biomaterials designed to replace the diseased cornea could be used to treat corneal blindness where human donor tissue is in short supply, but challenges are the integration of biomaterials with host tissue and cells, avoiding a rapid material degradation and maintaining corneal transparency. Additionally, implantation surgery often triggers an agg...

Homeostasis of the retinal pigment epithelium (RPE) is essential for the health and proper function of the retina. Regulation of RPE homeostasis is, however, largely unexplored, yet dysfunction of this process may lead to retinal degenerative diseases, including age-related macular degeneration (AMD). Here, we report that chemokine receptor CXCR5 r...

Homeostasis of the retinal pigment epithelium (RPE) is essential for the health and proper function of the retina. Regulation of RPE homeostasis is, however, largely unexplored, yet dysfunction of this process may lead to retinal degenerative diseases, including age-related macular degeneration (AMD). Here, we report that chemokine receptor CXCR5 r...

Objectives: Behçet's disease (BD) is characterised by repeated acute inflammatory attacks with aphthous ulcers of the oral mucosa, uveitis of the eyes, skin symptoms, and genital ulcers. Although its aetiology is still unknown, there is evidence of the involvement of oral bacteria in systemic diseases. Various types of oral bacteria may be involve...

Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in the elderly population. In our previous studies, we found that deficiency of CXCR5 causes AMD-like pathological phenotypes in mice, characterized by abnormalities and dysfunction of the retinal pigment epithelium (RPE) cells. The abnormalities included abno...

The CXCR5 (C-X-C motif chemokine receptor 5) is chemokine transmembrane receptor, acting via its ligand CXCL13 and plays a crucial role in controlling the trafficking of inflammatory cells into and from the sub-retinal space, which contributes to the pathogenesis of AMD. We have previously described the genetic ablation of CXCR5 deficiency causes R...

The objective of this study is to characterize the retinal degeneration (RD) phenotype of CXCR5/NRF2 double knockout (DKO) mice at the early adult age. CXCR5 KO mice and NRF2 KO mice were bred to create CXCR5/NRF2 DKO mice. The assessment of RD features included fundus and optical coherence tomography (OCT) imaging, periodic acid-Schiff (PAS), and...

Background: The ways in which microglia activate and promote neovascularization (NV) are not fully understood. Recent in vivo evidence supports the theory that calcium is required for the transition of microglia from a surveillance state to an active one. The objectives of this study were to discover novel L-type voltage-gated channel (L-VGCC) bloc...

Objective The aim of the present study is to investigate the clinical features of patients with Behcet’s disease (BD) in Mongolia.Methods Patients were identified and examined from six medical institutions in Mongolia from January 2015 to January 2019. BD was diagnosed according to the diagnostic criteria for BD established by the International Stu...

Glucose-6-Phosphate Dehydrogenase (G6PD) is a ubiquitous cytoplasmic enzyme converting glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway (PPP). The G6PD deficiency renders the inability to regenerate glutathione due to lack of Nicotine Adenosine Dinucleotide Phosphate (NADPH) and produces stress conditions that can cause...

Background: Retinal degenerative diseases affect millions of people and represent the leading cause of vision loss around the world. Retinal degeneration has been attributed to a wide variety of causes, such as disruption of genes involved in phototransduction, biosynthesis, folding of the rhodopsin molecule, and the structural support of the reti...

Background Retinal degenerative diseases affect millions of people and represent the leading cause of vision loss around the world. Retinal degeneration has been attributed to a wide variety of causes, such as disruption of genes involved in phototransduction, biosynthesis, folding of the rhodopsin molecule, and the structural support of the retina...

Background: Retinal degenerative diseases affect millions of people and represent the leading cause of vision loss around the world. Retinal degeneration has been attributed to a wide variety of causes, such as disruption of genes involved in phototransduction, biosynthesis, folding of the rhodopsin molecule, and the structural support of the retin...

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 co...

Retinal degenerative diseases affect millions of people and represent the leading cause of vision loss around the world. Retinal degeneration has been attributed to a wide variety of causes, such as disruption of genes involved in phototransduction, biosynthesis, folding of the rhodopsin molecule, and the structural support of the retina. The molec...

We report that placental growth factor (PlGF) negatively affects the endothelial cell (EC) barrier function through a novel regulatory mechanism. The PlGF mAb promotes (but recombinant protein disrupts) EC barrier function, thus affecting the barrier-forming protein levels, membrane distribution, and EC monolayer impedance by the electrical cell-im...

We report that placental growth factor (PlGF) negatively affects the endothelial cell (EC) barrier function through a novel regulatory mechanism. The PlGF mAb promotes (but recombinant protein disrupts) EC barrier function, thus affecting the barrier-forming protein levels, membrane distribution, and EC monolayer impedance by the electrical cell-im...

Inhibiting pathologic angiogenesis can halt disease progression, but such inhibition may offer only a temporary benefit, followed by tissue revascularization after treatment stoppage. This revascularization, however, occurs by largely unknown phenotypic changes in pathologic vessels. To investigate the dynamics of vessel reconfiguration during reva...

Previous research has shown that CXCR5 −/− mice develop retinal degeneration (RD) with age, a characteristic related to age macular degeneration (AMD). RD in these mice is not well-understood, and in this study, we sought to characterize further the RD phenotype and to gain mechanistic insights into the function of CXCR5 in the retina. CXCR5 −/− an...

Purpose: Treatment of corneal neovascularization can lead to vessel regression and recovery of corneal transparency. Here, we examined the response of the cornea to a repeated stimulus after initial vessel regression comparing the second wave of neovascularization with the first. Methods: Corneal neovascularization was induced by surgical suture...

Placental growth factor (PlGF or PGF) is a member of the VEGF family, which is known to play a critical role in pathological angiogenesis, inflammation, and endothelial cell barrier function. However, the molecular mechanisms by which PlGF mediates its effects in non-proliferative diabetic retinopathy (DR) remain elusive. In this study, we performe...

Retinal degenerative diseases affect millions of people and are the leading cause of vision loss. Retinal degeneration has been attributed to a wide variety of causes, such as disruption of genes that are involved in phototransduction, biosynthesis, folding of the rhodopsin molecule and the structural support of the retina. The molecular pathogenes...

Objective— Pathological neovascularization is crucial for progression and morbidity of serious diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. While mechanisms of ongoing pathological neovascularization have been extensively studied, the initiating pathological vascular remodeling (PVR) events, which precede neo...

Background Age-related macular degeneration (AMD) is the most common, progressive, and polygenic cause of irreversible visual impairment in the world. The molecular pathogenesis of the primary events of AMD is poorly understood. We have investigated a transcriptome-wide analysis of differential gene expression, single-nucleotide polymorphisms (SNPs...

Abstract Placental growth factor (PlGF or PGF), a member of the vascular endothelial growth factor (VEGF) sub-family, plays a crucial role in pathological angiogenesis and inflammation. However, the underlying molecular mechanisms that PlGF mediates regarding the complications of non-proliferative diabetic retinopathy (DR) remain elusive. Using an...

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...

Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-κB signaling pathway plays important roles in inflammation and angiogenesis. Here,...

Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowled...

Angiogenesis as a pathological process in the eye can lead to blindness. In the cornea, suppression of angiogenesis by anti-VEGF treatment is only partially effective while steroids, although effective in treating inflammation and angiogenesis, have broad activity leading to undesirable side effects. In this study, genome-wide expression was invest...

Purpose Astaxanthin (AST) has a strong antioxidant cellular membrane chaperone protective effect. Recently, a water-soluble nanosized AST (nano-AST) form was produced, which is expected to improve the efficacy of oral intake effects. The purpose of this study was to examine whether oral nano-AST has therapeutic effects on UV-induced photokeratitis...

Therapeutics against pathologic new blood vessel growth, particularly those targeting vascular endothelial growth factor (VEGF) are of enormous clinical interest. In the eye, where anti-VEGF agents are in widespread clinical use for treating retinal and corneal blindness, only partial or transient efficacy and resistance to anti-VEGF agents are amo...

Supplementary Table 1: Corneal epithelial thickness, 24 hours after UVB exposure, when treated with different doses of Nano-AST. Supplementary Table 2: Comparison of Nano-AST to other antioxidant treatments. Supplementary Table 3: Mean grey value DHE (ROS) staining in cornea. Supplementary Table 4: Quantification of TUNEL positive cells. Supplement...

In angiogenesis with concurrent inflammation, many pathways are activated, some linked to VEGF and others largely VEGF-independent. Pathways involving inflammatory mediators, chemokines, and micro-RNAs may play important roles in maintaining a pro-angiogenic environment or mediating angiogenic regression. Here, we describe a gene expression dataset...

Newly formed microcapillary networks arising in adult organisms by angiogenic and inflammatory stimuli contribute to pathologies such as corneal and retinal blindness, tumor growth, and metastasis. Therapeutic inhibition of pathologic angiogenesis has focused on targeting the VEGF pathway, while comparatively little attention has been given to remo...