RESUMEN
Four types of amide (C3; C28; C3-C28) conjugates based on 2,3-seco-18alphaH-oleanane and 2,3-secolupane mono- and dicarboxylic acids were synthesized. The range of diamide derivatives was supplemented with C3-C3' and C28-C28' dicondensed amides with two A-secotriterpene backbones educed by reacting monocarboxylic A-secoacids with biogenic amino acid lysine. Compounds with inhibitory action against herpes virus reproduction (EC50 8.7 and 4.1 McM) were found among the synthesized mono- and diamide derivatives containing an ethyl-beta-alaninate fragment. It has been ascertained that diamide with ethyl-beta-alaninate fragment combines anti-herpes virus properties and anti-HIV activity (EC50 5.1 McM). For active compounds, the maximum non-toxic concentration (MNTC)/EC50 ratios ranges from 9.7 to 40.8. The synthesized amide conjugates do not exhibit any marked cytotoxic effects against human tumor cell lines rabdomiosarcoma RD TE32, A549 lung carcinoma and melanoma MS.
Asunto(s)
Amidas/síntesis química , Antineoplásicos/síntesis química , Antivirales/química , Ácido Oleanólico/análogos & derivados , Triterpenos/química , Amidas/química , Amidas/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antivirales/síntesis química , Antivirales/farmacología , Línea Celular Tumoral , VIH-1/efectos de los fármacos , Humanos , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Simplexvirus/efectos de los fármacos , Triterpenos/síntesis química , Triterpenos/farmacología , Replicación Viral/efectos de los fármacosRESUMEN
Synthesis of dihydroquinopymaric acid amides and their 2beta-succinyl and 2beta-phthalyl derivatives containing residues of amino acids was carried out for the first time. Antiviral properties of the compounds synthesized were investigated.
Asunto(s)
Abietanos/química , Aminoácidos/química , Antivirales/química , Abietanos/farmacología , Aminoácidos/farmacología , Animales , Antivirales/farmacología , Células Cultivadas , Embrión de Pollo , Subtipo H7N7 del Virus de la Influenza A/efectos de los fármacosRESUMEN
The Beckman rearrangement of carboxy- and alkyloxycarbonylalkylamides of 3-hydroxyiminobetulonic acid led to derivatives of 3a-homo-4-aza-3-oxolup-20(29)-ene and 3,4-seco-2-cyanolupa-4(23),20(29)-diene. An X-ray analysis showed methyl 3-(N-acetoximino)lup-20(29)-enoate is the E-isomer. The compounds synthesized exhibited inhibiting activity toward the reproduction of flu A virus in cell culture.
Asunto(s)
Amidas/síntesis química , Aminoácidos/química , Antivirales/síntesis química , Virus de la Influenza A/efectos de los fármacos , Ácido Oleanólico/análogos & derivados , Replicación Viral/efectos de los fármacos , Amidas/química , Amidas/farmacología , Animales , Antivirales/química , Antivirales/farmacología , Células Cultivadas , Embrión de Pollo , Cristalografía por Rayos X , Fibroblastos/virología , Virus de la Influenza A/fisiología , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Ácido Oleanólico/farmacologíaRESUMEN
The preliminary studies mainly revealed comparable inhibition activities of 3-oxime of betulonic acid, 3beta-O-acetyl-28-O-hemiphthalate of betulin and 3,28-dioxime of betulin against reproduction of influenza viruses A (H1N1), A (H7N1), A (H3N2) and B, as well as against the strains of influenza virus A (H1N1) with intrinsic resistance to rimantadine and A (H7N1) with acquired resistance to the drug. The level of the activity depended on the system used for the virus reproduction. The highest level was observed under conditions providing higher permissibivity, i.e. in the chick embryo fibroblast cell culture for A (H7N1) and in fragments of chick embryo chorioallantoic membranes (for all the viruses). In the experiments with virus A/FPV/Rostock/34 (H7N1) in the chick embryo fibroblast cell culture the average effective concentrations (EC50) of the triterpene compounds were 10.4-17.5 mcM in comparison to EC50 of rimantadine (0.014 mcM). The use of every of the compounds in combination with rimantadine resulted in a 2-16 times decrease of their EC50 and correction of the concentration-effect relation of rimantadine. However, when rimantadine was used alone within the higher range of the nontoxic concentrations (11.6-57.6 mcM). its antiviral properties were significantly less pronounced. As a result the virus titer difference in comparison to the control within the above range of the rimantadine concentrations increased from < 1 to > 2.35 Ig PPU/ml and the relations of the maximal tolerance concentrations of the compounds to their EC50 increased 1.7-15.9 times.
Asunto(s)
Antivirales/farmacología , Virus de la Influenza A/fisiología , Virus de la Influenza B/fisiología , Gripe Humana/tratamiento farmacológico , Rimantadina/farmacología , Triterpenos/farmacología , Replicación Viral/efectos de los fármacos , Animales , Antivirales/química , Células Cultivadas , Embrión de Pollo , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/métodos , Humanos , Triterpenos/químicaAsunto(s)
Ciclosporina/farmacología , Proteínas de Transporte de Membrana Mitocondrial/fisiología , Estrés Oxidativo/fisiología , Triticum/fisiología , Frío , Proteínas de Transporte de Membrana Mitocondrial/efectos de los fármacos , Poro de Transición de la Permeabilidad Mitocondrial , Dilatación Mitocondrial/fisiología , Plantones/efectos de los fármacos , Plantones/fisiologíaRESUMEN
A reductive transformation of the peroxide products of ozonolysis of derivatives of 3beta-O-acetyl-22(17-->28)-abeo-lupa-17(28),20(29)-diene and the subsequent intramolecular ketalization led to a compound with a trioxane fragment. This is a new approach to a skeletal modification of triterpenoid cycle E. An activity of the synthesized compounds was found toward the viruses of type A influenza and herpes simplex.
Asunto(s)
Alphainfluenzavirus/efectos de los fármacos , Antivirales/química , Antivirales/farmacología , Simplexvirus/efectos de los fármacos , Triterpenos/química , Triterpenos/farmacología , Antivirales/síntesis química , Catálisis , Humanos , Compuestos de Rutenio/química , Saponinas/química , Triterpenos/síntesis químicaRESUMEN
Betulonic acid amides with aliphatic and heterocyclic amines and with L-amino acids were synthesized by the acid chloride method. Betulonic acid amide and L-methionine derivatives of betulonic acid and its 3-oxime effectively inhibit the influenza A virus. Betulonic acid octadecylamide is active against the herpes simplex type 1 virus. The conjugate of betulonic acid 3-oxime with L-methionine is also active toward HIV-1. The tested compounds mainly show no activity toward the ECHO6 virus, which is devoid of a coat. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.
Asunto(s)
Amidas/química , Aminoácidos/química , Antivirales/síntesis química , Antivirales/farmacología , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Animales , Células Cultivadas , Embrión de Pollo , VIH-1/efectos de los fármacos , Herpesvirus Humano 1/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Espectrofotometría InfrarrojaRESUMEN
Betulin and betulinic acid have been modified at the C-3 and C-28 positions and the antiviral activity of derivatives has been evaluated in vitro. It was found that simple modifications of the parent structure of lupane triterpenes produced highly effective agents against influenza A and herpes simplex type 1 viruses.
Asunto(s)
Antivirales/farmacología , Triterpenos/farmacología , Antivirales/química , Pruebas de Sensibilidad Microbiana , Triterpenos/químicaRESUMEN
New nitrogen-containing derivatives of betulinic and betulonic acids, hydrazides and N'-benzalhydrazides, were synthesized. Their antiviral activities toward of influenza A virus, herpes simplex type I virus, enterovirus ECHO6, and HIV-1 were studied in vitro. Betulinic acid 3-oxime was found to have the highest activity against the influenza virus. Betulonic acid, betulinic acid 4-chlorobenzalhydrazide, betulonic acid 3-oxime benzalhydrazide, and betulinic acid hydrazide inhibited the replication of herpes simplex type I virus. Betulinic acid hydrazide also showed antiviral activity toward HIV-1. All the derivatives of betulinic acid under study displayed a low antiviral activity toward enterovirus ECHO6.
Asunto(s)
Antivirales/química , Antivirales/farmacología , Hidrazinas/química , Triterpenos/química , Animales , Antivirales/síntesis química , Bioquímica/métodos , Células Cultivadas/virología , Embrión de Pollo , Evaluación Preclínica de Medicamentos/métodos , Enterovirus/efectos de los fármacos , VIH-1/efectos de los fármacos , Herpesvirus Humano 1/efectos de los fármacos , Humanos , Hidrazinas/síntesis química , Hidrazinas/farmacología , Virus de la Influenza A/efectos de los fármacos , Oximas/síntesis química , Oximas/química , Oximas/farmacología , Triterpenos Pentacíclicos , Relación Estructura-Actividad , Triterpenos/farmacología , Ácido BetulínicoRESUMEN
Antiviral properties of betulin, betulinic and betulonic acids were investigated in cell cultures infected with herpes simplex type I, influenza FPV/Rostock and ECHO 6 viruses. All studied triterpenes were active against herpes simplex virus. Betulin and especially betulinic acid also suppressed ECHO 6 virus reproduction.
Asunto(s)
Antivirales/farmacología , Ácido Oleanólico/análogos & derivados , Fitoterapia , Extractos Vegetales/farmacología , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Relación Dosis-Respuesta a Droga , Echovirus 6 Humano/efectos de los fármacos , Herpesvirus Humano 1/efectos de los fármacos , Humanos , Virus de la Influenza A/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Ácido Oleanólico/administración & dosificación , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico , Triterpenos Pentacíclicos , Corteza de la Planta , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Triterpenos/administración & dosificación , Triterpenos/farmacología , Triterpenos/uso terapéutico , Células Tumorales Cultivadas/efectos de los fármacos , Proteínas del Envoltorio Viral , Ácido BetulínicoRESUMEN
Ureides and carbamates of betulinic acid and its derivatives were prepared in good yields by interaction of betulinic acid, betulonic acid, and betulonic acid 3-oxime with amines, amino acids, and alcohols. Ureides of betulonic acid containing L-Val and L-Met residues were found to be effective against herpes simplex type 1 virus. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2003, vol. 29, no. 6; see also http://www.maik.ru.
Asunto(s)
Antivirales/síntesis química , Antivirales/farmacología , Triterpenos/síntesis química , Triterpenos/farmacología , Carbamatos/síntesis química , Carbamatos/farmacología , Espectroscopía de Resonancia Magnética , Triterpenos Pentacíclicos , Espectrofotometría Infrarroja , Ácido BetulínicoRESUMEN
BACKGROUND: Glaucoma is a blinding disease usually associated with high intraocular pressure (IOP). In some families, abnormal anterior segment development contributes to glaucoma. The genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. Bone morphogenetic proteins (BMPs) participate in various developmental processes. We tested the importance of Bmp4 gene dosage for ocular development and developmental glaucoma. RESULTS: Bmp4+/- mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and Schlemm's canal drainage structures. Mice with severe drainage structure abnormalities, over 80% or more of their angle's extent, have elevated IOP. The penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the C57BL/6J background and absent on some other backgrounds. On the C57BL/6J background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve. CONCLUSIONS: We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. The abnormalities are similar to those in human patients with developmental glaucoma. Thus, BMP4 is a strong candidate to contribute to Axenfeld-Rieger anomaly and other developmental conditions associated with human glaucoma. BMP4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the C57BL/6J background. Bmp4+/- mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.
Asunto(s)
Segmento Anterior del Ojo/crecimiento & desarrollo , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/fisiología , Presión Intraocular , Hipertensión Ocular/etiología , Animales , Segmento Anterior del Ojo/anomalías , Proteína Morfogenética Ósea 4 , Electrorretinografía , Anomalías del Ojo/etiología , Anomalías del Ojo/patología , Dosificación de Gen , Heterocigoto , Ratones , Ratones Endogámicos C57BL , Hipertensión Ocular/patología , Nervio Óptico/crecimiento & desarrollo , Fenotipo , Vasos Retinianos/crecimiento & desarrolloRESUMEN
Glaucoma is a heterogeneous eye disease and a major cause of blindness worldwide. Recently, primary open angle glaucoma (POAG)-associated mutations have been found in the trabecular meshwork inducible glucocorticoid response gene (TIGR), also known as the myocilin gene (MYOC), at the GLC1A locus on chromosome 1q21-q31. These mutations occurred in a subset of patients with juvenile- and adult-onset POAG and exhibited autosomal dominant inheritance. Ocular expression and its involvement in POAG suggest that TIGR/MYOC may have a role(s) in regulating intraocular pressure (IOP). Here, we report the generation and analysis of mice heterozygous and homozygous for a targeted null mutation in Myoc. Our study shows that Myoc mutant mice are both viable and fertile. Our in vivo findings further demonstrate that Myoc is not required for normal IOP or normal ocular morphology. The lack of a discernable phenotype in both Myoc-heterozygous and Myoc-null mice suggests that haploinsufficiency is not a critical mechanism for POAG in individuals with mutations in MYOC. Instead, disease-causing mutations in humans likely act by gain of function.
Asunto(s)
Proteínas del Ojo/fisiología , Glaucoma de Ángulo Abierto/patología , Glicoproteínas/fisiología , Animales , Proteínas del Citoesqueleto , Ojo/metabolismo , Ojo/patología , Proteínas del Ojo/genética , Expresión Génica , Marcación de Gen/métodos , Glicoproteínas/genética , Humanos , Presión Intraocular , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutagénesis , ARN MensajeroRESUMEN
BACKGROUND: Little is known about genetic factors affecting intraocular pressure (IOP) in mice and other mammals. The purpose of this study was to determine the IOPs of genetically distinct mouse strains, assess the effects of factors such as age, sex and time of day on IOP in specific strain backgrounds, and to assess the effects of specific candidate gene mutations on IOP. RESULTS: Based on over 30 studied mouse strains, average IOP ranges from approximately 10 to 20 mmHg. Gender does not typically affect IOP and aging results in an IOP decrease in some strains. Most tested strains exhibit a diurnal rhythm with IOP being the highest during the dark period of the day. Homozygosity for a null allele of the carbonic anhydrase II gene (Car2n) does not alter IOP while homozygosity for a mutation in the leptin receptor gene (Leprdb) that causes obesity and diabetes results in increased IOP. Albino C57BL/6J mice homozygous for a tyrosinase mutation (Tyrc-2J) have higher IOPs than their pigmented counterparts. CONCLUSIONS: Genetically distinct mouse strains housed in the same environment have a broad range of IOPs. These IOP differences are likely due to interstrain genetic differences that create a powerful resource for studying the regulation of IOP. Age, time of day, obesity and diabetes have effects on mouse IOP similar to those in humans and other species. Mutations in two of the assessed candidate genes (Lepr and Tyr) result in increased IOP. These studies demonstrate that mice are a practical and powerful experimental system to study the genetics of IOP regulation and disease processes that raise IOP to harmful levels.
Asunto(s)
Presión Intraocular , Ratones Endogámicos , Modelos Animales , Factores de Edad , Anestesia , Animales , Presión Sanguínea , Proteínas del Citoesqueleto , Ambiente , Proteínas del Ojo/genética , Femenino , Variación Genética , Glaucoma/genética , Glicoproteínas/genética , Presión Intraocular/genética , Masculino , Ratones , Ratones Endogámicos/genética , Ratones Endogámicos/fisiología , Monofenol Monooxigenasa/deficiencia , Mutación , Periodicidad , Ratas , Reproducibilidad de los Resultados , Factores de Riesgo , Factores Sexuales , Especificidad de la Especie , Factores de TiempoRESUMEN
BACKGROUND: The iridocorneal angle forms in the mammalian eye from undifferentiated mesenchyme between the root of the iris and cornea. A major component is the trabecular meshwork, consisting of extracellular matrix organized into a network of beams, covered in trabecular endothelial cells. Between the beams, channels lead to Schlemm's canal for the drainage of aqueous humor from the eye into the blood stream. Abnormal development of the iridocorneal angle that interferes with ocular fluid drainage can lead to glaucoma in humans. Little is known about the precise mechanisms underlying angle development. There are two main hypotheses. The first proposes that morphogenesis involves mainly cell differentiation, matrix deposition and assembly of the originally continuous mesenchymal mass into beams, channels and Schlemm's canal. The second, based primarily on rat studies, proposes that cell death and macrophages play an important role in forming channels and beams. Mice provide a potentially useful model to understand the origin and development of angle structures and how defective development leads to glaucoma. Few studies have assessed the normal structure and development of the mouse angle. We used light and electron microscopy and a cell death assay to define the sequence of events underlying formation of the angle structures in mice. RESULTS: The mouse angle structures and developmental sequence are similar to those in humans. Cell death was not detectable during the period of trabecular channel and beam formation. CONCLUSIONS: These results support morphogenic mechanisms involving organization of cellular and extracellular matrix components without cell death or atrophy.
Asunto(s)
Cámara Anterior/citología , Cámara Anterior/embriología , Malla Trabecular/citología , Malla Trabecular/embriología , Animales , Cámara Anterior/crecimiento & desarrollo , Cámara Anterior/ultraestructura , Muerte Celular/fisiología , Córnea/citología , Córnea/embriología , Córnea/crecimiento & desarrollo , Córnea/ultraestructura , Matriz Extracelular/fisiología , Matriz Extracelular/ultraestructura , Humanos , Iris/citología , Iris/embriología , Iris/crecimiento & desarrollo , Iris/ultraestructura , Ratones , Ratones Endogámicos A , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Endogámicos MRL lpr , Ratones Endogámicos , Microscopía Electrónica de Rastreo/métodos , Malla Trabecular/crecimiento & desarrollo , Malla Trabecular/ultraestructuraRESUMEN
BACKGROUND: Glaucoma is a common disease but its molecular etiology is poorly understood. It involves retinal ganglion cell death and optic nerve damage that is often associated with elevated intraocular pressure. Identifying genes that modify glaucoma associated phenotypes is likely to provide insights to mechanisms of glaucoma. We previously reported glaucoma in DBA/2J mice caused by recessive alleles at two loci, isa and ipd, that cause iris stromal atrophy and iris pigment dispersion, respectively. A approach for identifying modifier genes is to study the effects of specific mutations in different mouse strains. When the phenotypic effect of a mutation is modified upon its introduction into a new strain, crosses between the parental strains can be used to identify modifier genes. The purpose of this study was to determine if the effects of the DBA/2J derived isa and ipd loci are modified in strain AKXD-28/Ty. RESULTS: AKXD-28/Ty mice develop glaucoma characterized by intraocular pressure elevation, retinal ganglion loss, and optic nerve excavation. In AKXD-28/Ty, isa causes an iris stromal atrophy phenotype as in DBA/2J. However, the iris pigment dispersion phenotype associated with ipd in DBA/2J does not occur in AKXD-28/Ty. Additionally, a greater severity and speed of retinal and optic nerve damage following intraocular pressure elevation in AKXD-28/Ty compared to DBA/2J mice suggests that AKXD-28/Ty is more susceptible to pressure-induced cell death. CONCLUSIONS: The consequences of the ipd and isa mutations are modified in the AKXD-28/Ty background. These strains provide a resource for the identification of modifier genes that modulate pigment dispersion and susceptibility to pressure-induced cell death.
Asunto(s)
Predisposición Genética a la Enfermedad , Glaucoma/genética , Glaucoma/patología , Animales , Atrofia , Femenino , Glaucoma/diagnóstico , Iris/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Endogámicos , Mutación , Enfermedades del Nervio Óptico/genética , Enfermedades del Nervio Óptico/patología , Fenotipo , Epitelio Pigmentado Ocular/patología , Enfermedades de la Retina/genética , Enfermedades de la Retina/patología , Factores Sexuales , Especificidad de la EspecieRESUMEN
Anterior segment developmental disorders, including Axenfeld-Rieger anomaly (ARA), variably associate with harmfully elevated intraocular pressure (IOP), which causes glaucoma. Clinically observed dysgenesis does not correlate with IOP, however, and the etiology of glaucoma development is not understood. The forkhead transcription factor genes Foxc1 (formerly Mf1 ) and Foxc2 (formerly Mfh1 ) are expressed in the mesenchyme from which the ocular drainage structures derive. Mutations in the human homolog of Foxc1, FKHL7, cause dominant anterior segment defects and glaucoma in various families. We show that Foxc1 (+/-)mice have anterior segment abnormalities similar to those reported in human patients. These abnormalities include small or absent Schlemm's canal, aberrantly developed trabecular meshwork, iris hypoplasia, severely eccentric pupils and displaced Schwalbe's line. The penetrance of clinically obvious abnormalities varies with genetic background. In some affected eyes, collagen bundles were half normal diameter, or collagen and elastic tissue were very sparse. Thus, abnormalities in extracellular matrix synthesis or organization may contribute to development of the ocular phenotypes. Despite the abnormalities in ocular drainage structures in Foxc1 (+/-)mice, IOP was normal in almost all mice analyzed, on all genetic backgrounds and at all ages. Similar abnormalities were found in Foxc2 (+/-)mice, but no disease-associated mutations were identified in the human homolog FKHL14 in 32 ARA patients. Foxc1 (+/-)and Foxc2 (+/-)mice are useful models for studying anterior segment development and its anomalies, and may allow identification of genes that interact with Foxc1 and Foxc2 (or FKHL7 and FKHL14 ) to produce a phenotype with elevated IOP and glaucoma.
Asunto(s)
Segmento Anterior del Ojo/anomalías , Proteínas de Unión al ADN/genética , Ojo/embriología , Factores de Transcripción/genética , Animales , Cuerpo Ciliar/anomalías , Proteínas de Unión al ADN/fisiología , Factores de Transcripción Forkhead , Genotipo , Glaucoma/genética , Haplotipos , Heterocigoto , Humanos , Hibridación in Situ , Presión Intraocular/genética , Ratones , Ratones Mutantes , Microscopía Electrónica , Mutagénesis , Fenotipo , Especificidad de la Especie , Factores de Transcripción/fisiologíaRESUMEN
PURPOSE: To characterize ocular abnormalities associated with iris atrophy in DBA/2J mice and to determine whether mice of this strain develop elevated intraocular pressure (IOP) and glaucoma. METHODS: Different approaches, including slit-lamp biomicroscopy, ophthalmoscopic examination, ultrasound backscatter microscopy, and histology were used to examine the eyes of DBA/2J mice ranging from 2 to 30 months old. IOP was measured in DBA/2J mice of different ages. RESULTS: DBA/2J mice were found to develop pigment dispersion, iris transillumination, iris atrophy, anterior synechias, and elevated IOP. IOP was elevated in most mice by the age of 9 months. These changes were followed by the death of retinal ganglion cells, optic nerve atrophy, and optic nerve cupping. The prevalence and severity of these lesions increased with age. Optic nerve atrophy and optic nerve cupping was present in the majority of mice by the age of 22 months. CONCLUSIONS: DBA/2J mice develop a progressive form of secondary angle-closure glaucoma that appears to be initiated by iris atrophy and the associated formation of synechias. This mouse strain represents a useful model to evaluate mechanisms of pressure-related ganglion cell death and optic nerve atrophy, and to evaluate strategies for neuroprotection.