Despina Kokona

Glia antigen‐presenting cells (APCs) are pivotal regulators of immune surveillance within the retina, maintaining tissue homeostasis and promptly responding to insults. However, the intricate mechanisms underlying their local coordination and activation remain unclear. Our study integrates an animal model of retinal injury, retrospective analysis o...

Glia antigen-presenting cells (APCs) are pivotal regulators of immune surveillance within the retina, maintaining tissue homeostasis and promptly responding to insults. The intricate mechanisms underlying their local coordination and activation remain unclear. Our study integrates an animal model of retinal injury, retrospective analysis of human r...

Background Retinal degeneration results from disruptions in retinal homeostasis due to injury, disease, or aging and triggers peripheral leukocyte infiltration. Effective immune responses rely on coordinated actions of resident microglia and recruited macrophages, critical for tissue remodeling and repair. However, these phagocytes also contribute...

Macrophages/monocytes, the primary contributors to chronic inflammation in degenerated retinas, orchestrate intricate immune responses. They remain enigmatic in their local coordination and activation mechanisms. Innovations in experimental systems enable real-time exploration of immune cell interactions and temporal dimensions in response. In prec...

Background Clustering of microglia around the vasculature has been reported in the retina and the brain after systemic administration of lipopolysaccharides (LPS) in mice. LPS acts via activation of Toll-like receptor 4 (TRL4), which is expressed in several cell types including microglia, monocytes and vascular endothelial cells. The purpose of thi...

This study aims to investigate the effect of a systemic lipopolysaccharide (LPS) stimulus in the course of laser-induced choroidal neovascularization (CNV) in C57BL/6 J mice. A group of CNV-subjected mice received 1 mg/kg LPS via the tail vein immediately after CNV induction. Mouse eyes were monitored in vivo with fluorescein angiography for 2 week...

Aim: To compare choroidal neovascularization (CNV) lesion measurements obtained by in vivo imaging modalities, with whole mount histological preparations stained with isolectin GS-IB4, using a murine laser-induced CNV model. Methods: B6N.Cg-Tg(Csf1r-EGFP)1Hume/J heterozygous adult mice were subjected to laser-induced CNV and were monitored by fl...

The photoreceptor-specific nuclear receptor Nr2e3 is not expressed in Nr2e3rd7/rd7 mice, a mouse model of the recessively inherited retinal degeneration enhanced S-cone sensitivity syndrome (ESCS). We characterized in detail C57BL/6J Nr2e3rd7/rd7 mice in vivo by fundus photography, optical coherence tomography and fluorescein angiography and, post...

The endocannabinoid system has been shown to be a putative therapeutic target for retinal disease. Here, we aimed to investigate the ability of the endocannabinoid 2-arachidonoylglycerol (2-AG) and novel inhibitors of its metabolic enzymes, α/β-hydrolase domain-containing 6 (ABHD6) and monoacylglycerol lipase (MAGL), a) to protect the retina agains...

Purpose To investigate the effect of retinal microglia depletion, and the effect of systemic lipopolysaccharide (LPS) exposure, in the course of laser‐induced choroidal neovascularization (CNV) in mice. Methods For microglia depletion, C57BL6/J mice were kept under a diet containing the colony‐stimulating factor 1 receptor (CSF‐1R) inhibitor PLX56...

Neovascular age-related macular degeneration is one of the leading causes of blindness. Microglia and macrophages play critical role in choroidal neovascularization (CNV) and may therefore be potential targets to modulate the disease course. This study evaluated the effect of the colony stimulating factor-1 receptor (CSF-1R) inhibitor PLX5622 on ex...

The role of microglia in retinal inflammation is still ambiguous. Branch retinal vein occlusion initiates an inflammatory response whereby resident microglia cells are activated. They trigger infiltration of neutrophils that exacerbate blood-retina barrier damage, regulate postischemic inflammation and irreversible loss of neuroretina. Suppression...

Background Microglia-associated inflammation is closely related to the pathogenesis of various retinal diseases such as uveitis and diabetic retinopathy, which are associated with increased vascular permeability. In this study, we investigated the effect of systemic lipopolysaccharide (LPS) exposure to activation and proliferation of retinal microg...

BNN27, a C17-spiroepoxy derivative of DHEA, was shown to have anti-apoptotic properties via mechanisms involving the NGF receptors (TrkA/ p75NTR). In this study we examined the effects of BNN27 on neural/glial cell function, apoptosis and inflammation in the experimental rat streptozotocin (STZ)-model of diabetic retinopathy (DR). The ability of BN...

Spectral domain optical coherence tomography (SD-OCT) and scanning laser ophthalmoscopy (SLO) are extensively used in experimental ophthalmology. In the present protocol, mice expressing green fluorescent protein (gfp) under the promoter of Cx3cr1 (BALB/c-Cx3cr1gfp/gfp) were used to image microglia cells in vivo in the retina. Microglia are residen...

Purpose Activation of retinal microglia seems to have an influence on the outcome of retinal degenerative diseases. Recent studies show that systemic colony stimulating factor‐1 receptor (CSF‐1R) inhibition ablates microglia in the mouse central nervous system. However, the role of microglia inhibition in ischemic retinal disease remains unclear. T...

Purpose Retinal pathology such as diabetic retinopathy can be exacerbated by systemic viral illness. However, little is known whether systemic inflammation causes activation of retinal microglia. The aim of the present study was to investigate the effect of a systemic inflammatory stimulus with lipopolysaccharide (LPS) on retinal microglia activati...

This report provides sound evidence that the small molecule pharmaceutical PLX5622, a highly selective CSF-1R kinase inhibitor, crosses the blood–retina barrier and suppresses microglia activity. Members of this class of drug are in advanced clinical development stages and may represent a novel approach to modulate ocular inflammatory processes.

Purpose: To validate widefield autofluorescence (AF) in vivo imaging of the retina in mice expressing green fluorescent protein (gfp) in microglia, and to monitor retinal microglia reconstitution in vivo after lethal irradiation and bone marrow transplantation. Methods: Transgenic Cx3cr1gfp/gfp and wildtype Balb/c mice were used in this study. A...

Purpose: To characterize retinal microglia activation and macrophage recruitment in experimental branch retinal vein occlusion (BRVO). Methods: Experimental BRVO was induced in Balb/c mice and histologic changes were studied. Tissue hypoxia was visualized using pimonidazole hydrochloride. Monocyte-derived retinal cells were quantified using hist...

Anterior ischemic optic neuropathy (AION) is a relatively common cause of visual loss and results from hypoperfusion of the small arteries of the anterior portion of the optic nerve. AION is the leading cause of sudden optic nerve related vision loss with approximately 10 cases per 100′000 in the population over 50 years. To date there is no establ...

Purpose: Optical coherence tomography angiography (OCT-A) allows noninvasive visualization of retinal vessels in vivo. OCT-A was used to characterize the vascular network of the mouse retina and was compared with fluorescein angiography (FA) and histology. Methods: In the present study, OCT-A based on a Heidelberg Engineering Spectralis system w...

The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment...

Objectives: Diabetic retinopathy (DR) is a neovascular, inflammatory and neurodegenerative disease. Available therapeutics target only the neovascular component. Early pathological findings in the diabetic retina include amacrine and ganglion cell death and elevated levels of inflammatory cytokines. The neurosteroid Dehydroepiandrosterone (DHEA) af...

Purpose Anterior Ischemic Optic Neuropathy ( AION ) is a common cause of vision loss and is characterized by degeneration of the optic nerve and retinal ganglion cells. Recently, inflammation has been proposed to play a role in the course of AION , and we wanted to investigate the contribution of circulating and/or resident microglia. Methods We e...

Purpose: Diabetic Retinopathy (DR) is an important cause of blindness in people who suffer chronically from diabetes. The eye endures proliferative formation of new blood vessels and impairment of retinal neurons such as retinal ganglion and amacrine cells, leading to apoptotic processes (Lieth et al., 2000). The neovascularization component of DR...

Diabetic retinopathy (DR) is a neovascular, inflammatory and neurodegenerative disease. The neovascular component is treatable but no therapeutic agents are available for the other two components. Early changes in the diabetic retina include neuronal death of amacrine and retinal ganglion cells (RGC)(Barber et al., J Clin Invest,1998), and elevated...

Purpose: Diabetic retinopathy (DR) is characterized by a neovascular and a neurodegenerative component. While available treatments target the neovascular aspects of the disease, no therapy exists for the neurodegenerative component. Dehydroepiandrosterone (DHEA) and its spiro-epoxy derivative BNN27 were shown to have antiapoptotic activity [Caloger...

Purpose: Diabetic Retinopathy (DR) is a concomitant disease of both type I and type II Diabetes Mellitus, and it is responsible for visual impairment and blindness [1]. DR is the result of the combined actions of neovascularization and neurodegeneration processes [2]. While there are therapeutics available for the neovascularization component [3],...

Purpose The aim of the present study was to investigate the neuroprotective properties of SOM230, a new metabolically stable analogue of somatostatin, with a 12h plasma half‐life and high affinity for the sst1,2,3,5 receptor subtypes. Methods Female Sprague‐Dawley rats (250‐300g) were employed in an ex vivo model of retinal chemical ischemia and an...

Purpose Many retinopathies that lead to visual loss and blindness are characterized by neovascularization and neural retinal defects, such as a marked loss in retinal neurons and an increase in apoptosis. There are no therapeutic agents for the treatment of the neurodegenerative component of retinal disease. Immunohistochemistry and western blot me...

Purpose The aim of the present study was to investigate whether DHEA and NGF could protect retinal cells from cell death in an in vivo model of AMPA excitotoxicity. Methods Male and female Sprague‐Dawley rats (250‐300g) were administered intravitreally: AMPA (42 nmol per eye) or AMPA and DHEA (10‐6,10‐7M) or NGF (60pg/eye) or vehicle. A TrkA inhibi...

The involvement of striatal somatostatin receptors (sst(1), sst(2) and sst(4)) in locomotor activity was investigated. Male Sprague-Dawley rats, 280-350 g, received in the striatum bilateral infusions of saline, somatostatin, and selective sst(1), sst(2), and sst(4) ligands. Spontaneous locomotor activity was recorded for 60 min. The involvement of...