Radial optic neurotomy: a new surgical approach for glaucoma treatment?

Glaucoma is a leading cause of blindness worldwide, characterised by specific visual field defects due to the degeneration of retinal ganglion cells and damage to the optic nerve head (ONH). Elevated intraocular pressure (IOP) is the most important risk factor for glaucoma development. One of the clinical hallmarks of glaucomatous optic neuropathy is the excavation of the ONH, which consists of a progressive posterior displacement of the ONH surface and excavation of the pre-laminar tissues beneath the anterior-most aspect of the scleral canal, known as the anterior scleral ring. Radial optic neurotomy (RON) is a surgical technique that has been proposed for treating central retinal vein occlusion. While the original rationale of RON was the relief of increased tissue pressure within the optic nerve that results from occlusion of the central retinal vein, recent results are discussed here which suggest that by relaxing of the scleral ring of the prelaminar and laminar regions of the ONH, RON may alleviate the IOP-related connective tissue stress, and in turn, prevent the onset and reduce the progression of glaucomatous neuropathy.Fil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; ArgentinaFil: Belforte, Nicolás Adalberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; Argentin

Physiology of circadian entrainment

Mammalian circadian rhythms are controlled by endogenous biological oscillators, including a master clock located in the hypothalamic suprachiasmatic nuclei (SCN). Since the period of this oscillation is of ∼24 h, to keep synchrony with the environment, circadian rhythms need to be entrained daily by means of Zeitgeber (“time giver”) signals, such as the light-dark cycle. Recent advances in the neurophysiology and molecular biology of circadian rhythmicity allow a better understanding of synchronization. In this review we cover several aspects of the mechanisms for photic entrainment of mammalian circadian rhythms, including retinal sensitivity to light by means of novel photopigments as well as circadian variations in the retina that contribute to the regulation of retinal physiology. Downstream from the retina, we examine retinohypothalamic communication through neurotransmitter (glutamate, aspartate, pituitary adenylate cyclase-activating polypeptide) interaction with SCN receptors and the resulting signal transduction pathways in suprachiasmatic neurons, as well as putative neuron-glia interactions. Finally, we describe and analyze clock gene expression and its importance in entrainment mechanisms, as well as circadian disorders or retinal diseases related to entrainment deficits, including experimental and clinical treatments.Fil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rosenstein, Ruth Estela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Análisis de discapacidad visual en Buenos Aires, Argentina: La miopía patológica es la principal causa en edad laboral

Este trabajo estudia las causas de la discapacidad visual durante una década en la Ciudad de Buenos Aires. Se presenta una serie de casos retrospectiva donde se revisó la base de datos de certificados de discapacidad visual emitidos por el Ministerio de Salud de la Ciudad de Buenos Aires entre 2009 y 2017. En Argentina, la discapacidad visual se define como una agudeza visual ≤ 20/200 en el mejor ojo, o un campo visual correspondiente de menos de 20 grados en el ojo menos deteriorado. La base de datos incluyó las siguientes variables: año de emisión, edad, sexo y causa de la discapacidad visual. Entre 2009 y 2017 se certificaron un total de 7656 sujetos con ceguera legal. La edad media de la muestra fue de 57 ± 21 años y el 52.1% fueron mujeres. La distribución por edades mostró que el 62.8% de los certificados fueron dados a pacientes mayores de 50 años y que solo el 6.6% se otorgó a menores de 20 años. Las principales causas de discapacidad visual fueron la degeneración macular asociada a la edad (DMAE) (15.5%), la miopía degenerativa (14.4%), el glaucoma primario de ángulo abierto (11.3%) y la retinopatía diabética (6.6%). En los menores de 50 años, la miopía degenerativa fue la primera causa de discapacidad visual. Resulta interesante que, en Argentina, donde la prevalencia de miopía es baja, la miopía degenerativa sea la principal causa de discapacidad visual en adultos de mediana edad.This study assessed the causes of visual impairment over a decade in Buenos Aires City. This is a retrospective case series where we reviewed the database of visual disability certificates issued by the Buenos Aires City Ministry of Health between 2009 and 2017. In Argentina, visual disability is defined as a visual acuity ≤ 20/200 in the better eye, or a corresponding visual field of less than 20 degrees in the less impaired eye. The database included the following variables: year of issue, age, gender, and cause of visual disability. Between 2009 and 2017 a total of 7656 subjects were certified as legally blind. The mean age of the sample was 57 ± 21 years and 52.1% were females. The emission was near 700 certificates per year. The age distribution showed that 62.8% of certificates were from patients older than 50 years and that only 6.6% were given to subjects under 20. The leading causes of visual disability in Buenos Aires City were age-related macular degeneration (ARMD) with a rate of 15.5%, degenerative myopia (14.4%), primary open-angle glaucoma (11.3%) and diabetic retinopathy (6.6%). In subjects younger than 50, degenerative myopia was the first cause of visual disability. Interestingly in Argentina, where the prevalence of myopia is low, degenerative myopia is found to be the major cause of visual disability in middle-aged adult subjects. Population and clinical methods to avoid this preventable disease should need to be implemented as a matter of urgency.Fil: Franco, Pablo Javier. Hospital Santa Lucía; ArgentinaFil: Suwezda, Alejandro. Fundacion Hospitalaria; ArgentinaFil: Schlottmann, Patricio. Organizacion Medica de Investigacion (omi);Fil: Destefanis, María Pía. Hospital Santa Lucía; ArgentinaFil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; ArgentinaFil: Iribarren, Rafael. No especifíca;Fil: Grzybowski, Andrzej. Institute For Research In Ophthalmology; Poloni

Global and Ocular Hypothermic Preconditioning Protect the Rat Retina from Ischemic Damage

Retinal ischemia could provoke blindness. At present, there is no effective treatment against retinal ischemic damage. Strong evidence supports that glutamate is implicated in retinal ischemic damage. We investigated whether a brief period of global or ocular hypothermia applied 24 h before ischemia (i.e. hypothermic preconditioning, HPC) protects the retina from ischemia/reperfusion damage, and the involvement of glutamate in the retinal protection induced by HPC. For this purpose, ischemia was induced by increasing intraocular pressure to 120 mm Hg for 40 min. One day before ischemia, animals were submitted to global or ocular hypothermia (33uC and 32uC for 20 min, respectively) and fourteen days after ischemia, animals were subjected to electroretinography and histological analysis. Global or ocular HPC afforded significant functional (electroretinographic) protection in eyes exposed to ischemia/reperfusion injury. A marked alteration of the retinal structure and a decrease in retinal ganglion cell number were observed in ischemic retinas, whereas global or ocular HPC significantly preserved retinal structure and ganglion cell count. Three days after ischemia, a significant decrease in retinal glutamate uptake and glutamine synthetase activity was observed, whereas ocular HPC prevented the effect of ischemia on these parameters. The intravitreal injection of supraphysiological levels of glutamate induced alterations in retinal function and histology which were significantly prevented by ocular HPC. These results support that global or ocular HPC significantly protected retinal function and histology from ischemia/reperfusion injury, probably through a glutamatedependent mechanism.Fil: Salido E.Fil: Dorfman D.Fil: Bordone, Melina.Fil: Chianelli Mónica S.Fil: González Fleitas Mf.Fil: Rosenstein Re

Effect of chondroitin sulfate on intraocular pressure in rats

PURPOSE: To study the effect of intracameral injections of chondroitin sulfate (CS) on intraocular pressure (IOP), retinal function, and histology in rats. METHODS: Acute or chronic injections of CS were performed unilaterally in the rat anterior chamber, whereas the contralateral eye was injected with vehicle. IOP was daily or weekly assessed by a tonometer. Retinal function was assessed by scotopic electroretinography (ERG) and the visual pathway by flash visual evoked potentials (VEPs), whereas the retinal and optic nerve head structure were examined by histologic analysis. RESULTS: A single injection of 8 mg (but not 2 or 4 mg) CS induced a significant increase of IOP. The increase of IOP induced by a single injection of 8 mg CS lasted for 7 days, whereas chronic (weekly) administration during 10 weeks induced a significant and sustained increase in IOP compared with eyes injected with vehicle. A significant decrease of scotopic ERG a- and b- wave amplitude was observed after 6 and 10 weeks of CS administration. Moreover, a significant decrease in scotopic flash VEP N2-P2 component amplitude was observed in eyes treated with CS for 6 and 10 weeks. A significant loss of ganglion cell layer cells and optic nerve axons was observed in eyes receiving CS for 10 weeks. CONCLUSIONS: These results suggest that exogenous CS simulates the accumulation of CS in primary open-angle glaucoma and that increased amounts of CS could play a key role in the IOP dysregulation characteristic of glaucoma.Fil: Belforte, Nicolás Adalberto. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Sande Casal, Pablo Horacio. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Zavalia, Nuria Maria Asuncion. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Knepper, Paul A.. University of Illinois; Estados UnidosFil: Rosenstein, Ruth Estela. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration

Non-exudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. The macular retinal pigment epithelium (RPE) lies in a high oxidative environment because its high metabolic demand, mitochondria concentration, reactive oxygen species levels, and macular blood flow. It has been suggested that oxidative stress-induced damage to the RPE plays a key role in NE-AMD pathogenesis. The fact that the disease limits to the macular region raises the question as to why this area is particularly susceptible. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks exclusively circumscribed to the temporal region of the RPE/outer retina. The aim of this work was analyzing RPE regional differences that could explain AMD localized susceptibility. Lower melanin content, thicker basal infoldings, higher mitochondrial mass, and higher levels of antioxidant enzymes, were found in the temporal RPE compared with the nasal region. Moreover, SCGx induced a decrease in the antioxidant system, and in mitochondria mass, as well as an increase in mitochondria superoxide, lipid peroxidation products, nuclear Nrf2 and heme oxygenase-1 levels, and in the occurrence of damaged mitochondria exclusively at the temporal RPE. These findings suggest that despite the well-known differences between the human and mouse retina, it might not be NE-AMD pathophysiology which conditions the localization of the disease, but the macular RPE histologic and metabolic specific attributes that make it more susceptible to choroid alterations leading initially to a localized RPE dysfunction/damage, and secondarily to macular degeneration.Fil: Dieguez, Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Romeo, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Alaimo, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: González Fleitas, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Aranda, Marcos Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Dorfman, Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Melatonin prevents early pituitary dysfunction induced by sucrose-rich diets

While physiological levels of glucocorticoids are required to ensure proper functions of the body, consistently high levels may engender several deleterious consequences. We have previously shown an increase in the activity of the hypothalamic-pituitary-adrenal (HPA) axis in rats fed sucrose-rich diets (SRD). The main goal of this study was to analyze the processes involved in the modulation of the pituitary production of ACTH by SRD, and to test melatonin as a possible therapeutic agent for the prevention of the HPA axis dysfunction. Male Wistar rats were fed standard chow and either SRD (30% sucrose in the drinking water) or plain water for three weeks. Melatonin was administered as subcutaneous pellets. Results showed that SRD treatment induced an increase in systemic ACTH and corticosterone levels and a decrease in melatonin levels. In the pituitary gland, we also detected an increase in the expression levels of proopiomelanocortin (POMC) that was accompanied by increased levels of: lipoperoxides, nitro-tyrosine modified proteins, catalase, heme oxygenase-1, interleukin-1β mRNA, and by an increase in the tissue number of inflammatory cells (F4/80 and Iba-1 positive cells). Melatonin treatment prevented all these systemic and pituitary changes as well as the increase in POMC expression induced by incubation of AtT-20 corticotrophs with conditioned media obtained from stimulated macrophages. In conclusion, stimulation of POMC/ACTH production in rats fed a SRD could involve the generation of oxidative stress and inflammation in the pituitary gland. Melatonin treatment prevented these effects and normalized the activity of the HPA axis.Fil: Mercau, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Calanni, Juan Salvador. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Aranda, Marcos Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Caldareri, Lilian Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Repetto, Esteban Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Cymeryng, Cora Betriz. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

New actors in optic neuritis pathogenesis

The aim of the present report was to analyze the involvement of glutamate neurotoxicity in retinal ganglion cell loss and optic nerve damage induced by experimental optic neuritis. For this purpose, the authors used an optic neuritis model induced by immunisation with myelin oligodendrocyte glycoprotein (AON). The authors describe a correlation in the timing of retinal ganglion cell (RGC) loss with alterations in the optic nerve actin cytoskeleton dynamic, and visual dysfunction. In addition, they show that an intravitreal injection of glutamate mimics, and an NMDA receptor antagonist avoids the effect of pre-clinical AON on visual functions and RGC number, as well as on optic nerve actin cytoskeleton. Taken together, their results support that avoiding glutamate neurotoxicity could become a new therapeutic approach for optic neuritis treatment.Fil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Induction of ischemic tolerance as a promising treatment against diabetic retinopathy

Diabetic retinopathy is a leading cause of acquired blindness, and it is the most common ischemic disorder of the retina. Available treatments are not very effective. Efforts to inhibit diabetic retinopathy have focused either on highly specific therapeutic approaches for pharmacologic targets or using genetic approaches to change expression of certain enzymes. However, it might be wise to choose innovative treatment modalities that act by multiple potential mechanisms. The resistance to ischemic injury, or ischemic tolerance, can be transiently induced by prior exposure to a non-injurious preconditioning stimulus. A complete functional and histologic protection against retinal ischemic damage can be achieved by previous preconditioning with non-damaging ischemia. In this review, we will discuss evidence that supports that ischemic conditioning could help avert the dreaded consequences that results from retinal diabetic damage.Fil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; ArgentinaFil: Fernandez, Diego Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental; Argentin