Abstract The retinal pigment epithelium ( RPE ), a monolayer located between the photoreceptors and choroid, is constantly damaged by oxidative stress, particularly because of reactive oxygen species ROS ). As , its physiological functions, essential for survival retina, any sustained damage may consequently lead to loss vision. Exosomes are small membranous vesicles released into extracellular medium numerous cell types, including cells. Their cargo includes genetic material proteins,...

Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes blindness in developed world. RP is at present untreatable and underlying neurodegenerative mechanisms are unknown, even though genetic often established. Acetylation deacetylation histones, carried out by histone acetyltransferases (HATs) deacetylases (HDACs), respectively, affects cellular division, differentiation, death survival. We found acetylation histones probably...

We have explored the mechanisms underlying ethanol-induced mitochondrial dynamics disruption and mitophagy. Ethanol increases fission in a concentration-dependent manner through Drp1 translocation OPA1 proteolytic cleavage. ARPE-19 (a human retinal pigment epithelial cell line) cells challenged with ethanol showed potential disruptions mediated by alterations complex IV protein level reactive oxygen species production. In addition, activated canonical autophagic pathway, as denoted...

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation enzymes belonging to the poly-ADP-ribose polymerase (PARP) was shown be involved photoreceptor degeneration human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated exact relevance predominant isoform - PARP1 cell death using knock-out (KO) mice. In vivo ex morphological...

Approximately 36 000 cases of simplex and familial retinitis pigmentosa (RP) worldwide are caused by a loss in phosphodiesterase (PDE6) function. In the preclinical Pde6α(nmf363) mouse model this disease, defects α-subunit PDE6 result progressive photoreceptors neuronal We hypothesized that increasing PDE6α levels using an AAV2/8 gene therapy vector could improve photoreceptor survival retinal utilized with cell-type-specific rhodopsin (RHO) promoter: AAV2/8(Y733F)-Rho-Pde6α, to transduce...

Abstract Autophagy and exosome secretion play important roles in a variety of physiological disease states, including the development age‐related macular degeneration. Previous studies have demonstrated that these cellular mechanisms share common pathways activation. Low oxidative damage ARPE ‐19 cells, alters both autophagy biogenesis. Moreover, stress modifies protein genetic cargo exosomes, possibly affecting fate surrounding cells. In order to understand connection between two their...

Retinal pigment epithelium has a crucial role in the physiology and pathophysiology of retina due to its location metabolism. Oxidative damage been demonstrated as pathogenic mechanism several retinal diseases, reactive oxygen species are certainly important by-products ethanol (EtOH) Autophagy shown exert protective effect different cellular animal models. Thus, our model, EtOH treatment increases autophagy flux, concentration-dependent manner. Mitochondrial morphology seems be clearly...

Abstract miR‐205‐5p is known to be involved in VEGF‐related angiogenesis and seems regulate associated cell signalling pathways, such as migration, proliferation apoptosis. Therefore, several studies have focused on the potential role of an anti‐angiogenic factor. Vascular observed diabetic retinopathy ‘wet’ form age‐related macular degeneration. Today, most common treatments against these eye‐related diseases are anti‐VEGF therapies. In addition, both AMD DR typically with oxidative stress;...

ARPE-19 retinal pigment epithelial cells cultured in a medium containing 35 mM D-glucose led to an augmented ROS formation and release of vascular endothelial factor (VEGF)-containing exosomes compared 5 (standard medium). Exposing these the melanocortin receptor agonist (MCR5) PG-901 (10−10M), for 9 d reduced generation, number released their VEGF content. In contrast, incubating with MCR1 BMS-470539 (10−5 M) or mixed MCR3/4 MTII (0.30 nmol) did not produce any significant decrease levels....

High glucose levels may cause vascular alterations in patients with diabetes, which can lead to complications such as diabetic retinopathy-an abnormal growth of retinal blood vessels. The micro-RNA miR-205-5p is known regulate angiogenesis by modulating the expression endothelial factor (VEGFA) different systems. This study investigates role controlling VEGFA both vitro and eye under hyperglycemic conditions. An alloxan-induced mouse model pigment epithelium human cell line (ARPE-19) were...

Deficiencies in rod-specific cyclic guanosine monophosphate (cGMP) phosphodiesterase-6 (PDE6) are the third most common cause of autosomal recessive retinitis pigmentosa (RP).Previously, viral gene therapy approaches on pre-clinical models with mutations PDE6 have demonstrated that photoreceptor cell survival and visual function can be rescued when virus is delivered into subretinal space before onset disease.However, no studies currently been published analyze rescue effects after disease...

The third-most common cause of autosomal recessive retinitis pigmentosa (RP) is due to defective cGMP phosphodiesterase-6 (PDE6). Previous work using viral gene therapy on PDE6-mutant mouse models demonstrated photoreceptors can be rescued if administered before degeneration. However, whether visual function after degeneration onset has not been addressed. This a clinically important question, as newly diagnosed patients exhibit considerable loss rods and cones in their peripheral retinas....

Abstract Retinitis Pigmentosa is a group of inherited neurodegenerative diseases that result in selective cell death photoreceptors. In the developed world, RP regarded as main cause blindness among working age population. The precise mechanisms eventually leading to remain unknown and date no adequate treatment for available. Poly ADP ribose polymerase (PARP) over activity involved photoreceptor degeneration pharmacological inhibition or genetic knock-down PARP1 protect photoreceptors mice...

Mutations in Pde6b lead to high levels of signaling molecules cyclic guanosine monophosphate (cGMP) and Ca 2+ , which ultimately result photoreceptor cell death certain forms retinitis pigmentosa (RP). The level cGMP, is controlled by opposing activities guanylate cyclase (GUCY) phosphodiesterase-6 (PDE6), regulates the opening nucleotide-gated ion channels [CNG] thereby controls influx into outer segments. Using a lentiviral gene therapy approach, we have previously shown that degeneration...

Abstract Age related macular degeneration (AMD) is a common retina-related disease leading to blindness. Little known on the origin of disease, but it well documented that oxidative stress generated in retinal pigment epithelium and choroid neovascularization are closely involved. The study circulating miRNAs opening new possibilities terms diagnosis therapeutics. can travel associated lipoproteins or inside small Extracellular Vesicles (sEVs). A number reports indicate significant...

Rhodopsin is the G protein-coupled receptor in charge of initiating signal transduction rod photoreceptor cells upon arrival photon. D190N (RhoD190n), a missense mutation rhodopsin, causes autosomal-dominant retinitis pigmentosa (adRP) humans. Affected patients present hyperfluorescent retinal rings and progressive degeneration. Studies humans cannot reveal molecular processes causing earliest stages condition, thus necessitating creation an appropriate animal model. A knock-in mouse model...

Extracellular vesicles are released from cells under diverse conditions. Widely studied in cancer, they associated with different diseases playing major roles. Recent reports indicate that oxidative damage promotes the release of small extracellular vesicle (sEVs) retinal pigment epithelium (RPE), an angiogenic outcome and changes micro-RNA (miRNA) levels. The aim this study was to determine role miRNA miR-302a-3p, included within RPE-released sEVs, as regulator cultures endothelial (HUVEC)....

Purpose: Cytochrome p450 2E1 (CYP2E1) is a detoxifying enzyme with particular affinity for ethanol (EtOH) expressed in several tissues. Although CYP2E1 has been identified human RPE, nothing known about its metabolic activity. Expression of and activity after EtOH exposure have studied RPE ARPE-19 cells. Methods: Ethanol-induced mRNA expression was analyzed by RT-PCR quantitative PCR (qPCR) from donor as well protein determined Western blot. Cytoplasmic location also demonstrated...

Animal-assisted therapy (AAT) is a complementary intervention of that has shown positive results in the treatment various pathologies. This study assesses viability implementation and effectiveness an AAT program patients diagnosed with substance abuse disorder associated mental disorders (dual pathology). For study, dynamic prospective cohort was used, consisting 43 residential treatment. The consisted 10 sessions duration about 60 min, where data collected 3rd, 6th 10th sessions. Life...

This review focuses on the role of small extracellular vesicles in pathophysiological mechanisms retinal degenerative diseases. Many these are related or modulated by oxidative burden cells. It has been recently demonstrated that cellular communication retina involves and their rate release cargo features might be affected environment some instances also mediated autophagy. The fate is diverse, could end up circulation used as markers, target neighbour cells modulating gene protein...

Exosomes or small extracellular vesicles (sEVs) represent a pivotal component in intercellular communication, carrying diverse array of biomolecules. Several factors can affect sEVs release dynamics, as occurs hyperglycemia inflammation. In fact, has been associated with the promotion physio-pathological processes. Among cargo, microRNAs play an essential role cell-to-cell regulation. More concretely, miR-205-5p is related to angiogenesis and cell proliferation. The aim this study understand...