New Insights on Dietary Polyphenols for the Management of Oxidative Stress and Neuroinflammation in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a neurodegenerative and vascular pathology that is considered one of the leading causes of blindness worldwide, resulting from complications of advanced diabetes mellitus (DM). Current therapies consist of protocols aiming to alleviate the existing clinical signs associated with microvascular alterations limited to the advanced disease stages. In response to the low resolution and limitations of the DR treatment, there is an urgent need to develop more effective alternative therapies to optimize glycemic, vascular, and neuronal parameters, including the reduction in the cellular damage promoted by inflammation and oxidative stress.

The Role of Cannabinoids in CNS Development: Focus on Proliferation and Cell Death.

The active principles of Cannabis sativa are potential treatments for several diseases, such as pain, seizures and anorexia. With the increase in the use of cannabis for medicinal purposes, a more careful assessment of the possible impacts on embryonic development becomes necessary. Surveys indicate that approximately 3.

Gut microbiota: A potential therapeutic target for management of diabetic retinopathy?

Diabetic Retinopathy (DR) is one of the main complications of Diabetes Mellitus (DM), drastically impacting individuals of working age over the years, being one of the main causes of blindness in the world. The existing therapies for its treatment consist of measures that aim only to alleviate the existing clinical signs, associated with the microvasculature. These treatments are limited only to the advanced stages and not to the preclinical ones.

Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve: galectin-3 participation.

Diabetes is a lifelong disease characterized by glucose metabolic imbalance, in which low insulin levels or impaired insulin signaling lead to hyperglycemic state. Within 20 years of diabetes progression, 95% of patients will have diabetic retinopathy, the leading cause of visual defects in working-age people worldwide. Although diabetes is considered a microvascular disease, recent studies have shown that neurodegeneration precedes vascular changes within the diabetic visual system, albeit its mechanisms are still under investigation.

Caffeine regulates GABA transport via AR blockade and cAMP signaling.

Caffeine is the most consumed psychostimulant drug in the world, acting as a non-selective antagonist of adenosine receptors AR and AR, which are widely expressed in retinal layers. We have previously shown that caffeine, when administered acutely, acts on AR to potentiate the NMDA receptor-induced GABA release. Now we asked if long-term caffeine exposure also modifies GABA uptake in the avian retina and which mechanisms are involved in this process.

Regulation of the Serotonergic System by Kainate in the Avian Retina.

Serotonin (5-HT) has been recognized as a neurotransmitter in the vertebrate retina, restricted mainly to amacrine and bipolar cells. It is involved with synaptic processing and possibly as a mitogenic factor. We confirm that chick retina amacrine and bipolar cells are, respectively, heavily and faintly immunolabeled for 5-HT.

Cannabinoids Induce Cell Death and Promote P2X7 Receptor Signaling in Retinal Glial Progenitors in Culture.

Development of progenitors in the embryonic retina is modulated by signaling molecules, and cannabinoid receptors are highly expressed in the early developing retina. Here, we investigated whether the CB1/CB2 receptor agonist WIN 5212-2 (WIN) modulated the proliferation, viability, and calcium responses in chick embryo retinal progenitors in culture. A decline in [H]-thymidine incorporation was observed when cultures were incubated with 0.

Chlorogenic acids inhibit glutamate dehydrogenase and decrease intracellular ATP levels in cultures of chick embryo retina cells.

Chlorogenic acids (CGAs) are a group of phenolic compounds found in worldwide consumed beverages such as coffee and green tea. They are synthesized from an esterification reaction between cinnamic acids, including caffeic (CFA), ferulic and p-coumaric acids with quinic acid (QA), forming several mono- and di-esterified isomers. The most prevalent and studied compounds are 3-O-caffeoylquinic acid (3-CQA), 4-O-caffeoylquinic acid (4-CQA) and 5-O-caffeoylquinic acid (5-CQA), widely described as having antioxidant and cell protection effects.

Lack of Galectin-3 attenuates neuroinflammation and protects the retina and optic nerve of diabetic mice.

Diabetic retinopathy is the leading cause of acquired blindness in working-age individuals. Recent work has revealed that neurodegeneration occurs earlier than vascular insult and that distal optic nerve damage precedes retinal degeneration and vascular insult. Since we have shown that optic nerve degeneration is reduced after optic nerve crush in Galectin-3 knockout (Gal-3 -/-) mice, we decided to investigate whether Gal-3 -/- could relieve inflammation and preserve both neurons and the structure of the retina and optic nerve following 8 weeks of diabetes.

The (Na(+)/K (+))-ATPase activity in the developing rat retina: the role of insulin-like growth factor-I (IGF-I).

In this work, the (Na(+)/K(+))-ATPase activity was evaluated during the early stages of the postnatal development of rat retina and showed an almost three-time increase from P0 to P14. Expression of the three catalytic subunit isoforms (α1, α2, and α3) of the (Na(+)/K(+))-ATPase was also evaluated by immunoblot in the same period, but no correlation to the catalytic activity increment was observed. On the other hand, immunolocalization of these three α-catalytic isoforms in the developing retina showed an age-related pattern.

Expression of A1 adenosine receptors in the developing avian retina: in vivo modulation by A(2A) receptors and endogenous adenosine.

Little is known about the mechanisms that regulate the expression of adenosine receptors during CNS development. We demonstrate here that retinas from chick embryos injected in ovo with selective adenosine receptor ligands show changes in A1 receptor expression after 48 h. Exposure to A1 agonist N⁶-cyclohexyladenosine (CHA) or antagonist 8-Cyclopentyl-1, 3-dipropylxanthine (DPCPX) reduced or increased, respectively, A1 receptor protein and [³H]DPCPX binding, but together, CHA+DPCPX had no effect.

Neurochemical phenotype and birthdating of specific cell populations in the chick retina.

The chick embryo is one of the most traditional models in developing neuroscience and its visual system has been one of the most exhaustively studied. The retina has been used as a model for studying the development of the nervous system. Here, we describe the morphological features that characterize each stage of the retina development and studies of the neurogenesis period of some specific neurochemical subpopulations of retinal cells by using a combination of immunohistochemistry and autoradiography of tritiated-thymidine.

Ethanol increases GABA release in the embryonic avian retina.

Several mechanisms underlying ethanol action in GABAergic synapses have been proposed, one of these mechanisms is on GABA release. Here, we report that in ovo exposure to ethanol induces an increase on GABA release in the embryonic chick retina. Eleven-day-old chick embryos (E11) received an injection of either phosphate buffer saline (PBS) or ethanol (10%, v/v, diluted in PBS), and were allowed to develop until E16.

Glutamate receptors modulate sodium-dependent and calcium-independent vitamin C bidirectional transport in cultured avian retinal cells.

Vitamin C is transported in the brain by sodium vitamin C co-transporter 2 (SVCT-2) for ascorbate and glucose transporters for dehydroascorbate. Here we have studied the expression of SVCT-2 and the uptake and release of [(14)C] ascorbate in chick retinal cells. SVCT-2 immunoreactivity was detected in rat and chick retina, specially in amacrine cells and in cells in the ganglion cell layer.

Signal transduction pathways associated with ATP-induced proliferation of cell progenitors in the intact embryonic retina.

ATP and ADP induce retinal cell proliferation through activation of PKC and extracellular signal-regulated kinases (ERKs). Here, we characterized the effect of purinergic agonists on the turnover of phosphoinositides and activation of ERKs during development of the chick embryo retina. When intact retinas were incubated with ATP, ADP or UTP, a dose-dependent accumulation of [(3)H]-phosphoinositides was observed (% of control, EC(50): 548+/-20.

Local differences in GABA release induced by excitatory amino acids during retina development: selective activation of NMDA receptors by aspartate in the inner retina.

Glutamate and GABA are the major excitatory and inhibitory neurotransmitters in the CNS. In the retina, it has been shown that glutamate and aspartate and their agonists kainate and NMDA promote the release of GABA. In the chick retina, at embryonic day 14 (E14), glutamate and kainate were able to induce the release of GABA from amacrine and horizontal cells as detected by GABA-immunoreactivity.

GABA(Abeta2-3) immunoreactive cells in the developing chick retina.

Gama-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). It has been shown that GABA is an important factor for CNS maturation and that its functions are mainly mediated by GABA(A) receptors. Thus, in order to fully comprehend the role of GABA during development, it is essential to establish the developmental features of the catalytic subunits (beta) of GABA(A) receptor.