Global RNAseq of ocular cells reveals gene dysregulation in both asymptomatic and with Congenital Zika Syndrome infants exposed prenatally to Zika virus.

In 2015, Brazil reported an outbreak identified as Zika virus (ZIKV) infection associated with congenital abnormalities. To date, a total of 86 countries and territories have described evidence of Zika infection and recently the appearance of the African ZIKV lineage in Brazil highlights the risk of a new epidemic. The spectrum of ZIKV infection-induced alterations at both cellular and molecular levels is not completely elucidated. Here, we present for the first time the gene expression responses associated with prenatal ZIKV infection from ocular cells. We applied a recently developed non-invasive method (impression cytology) which use eye cells as a model for ZIKV studies. The ocular profiling revealed significant differences between exposed and control groups, as well as a different pattern in ocular transcripts from Congenital Zika Syndrome (CZS) compared to ZIKV-exposed but asymptomatic infants. Our data showed pathways related to mismatch repair, cancer, and PI3K/AKT/mTOR signaling and genes probably causative or protective in the modulation of ZIKV infection. Ocular cells revealed the effects of ZIKV infection on primordial neuronal cell genes, evidenced by changes in genes associated with embryonic cells. The changes in gene expression support an association with the gestational period of the infection and provide evidence for the resulting clinical and ophthalmological pathologies. Additionally, the findings of cell death- and cancer-associated deregulated genes raise concerns about the early onset of other potential pathologies including the need for tumor surveillance. Our results thus provide direct evidence that infants exposed prenatally to the Zika virus, not only with CZS but also without clinical signs (asymptomatic) express cellular and molecular changes with potential clinical implications.

Manifestações oftalmológicas dos pacientes idosos com infecção pelo vírus da imunodeficiência humana / Ophthalmologic manifestations of elderly patients with human immunodeficiency virus infection

Resumo Objetivos: Identificar e descrever as alterações oculares em idosos com HIV ou aids através de exame oftalmológico. Avaliar a associação entre as alterações oculares encontradas e o nível de linfócitos T CD4, tempo da terapia antirretroviral, características demográficas e faixa etária. Métodos: Série de 40 casos de pacientes idosos com HIV examinados nos serviços de oftalmologia e imunologia do Hospital Universitário Gaffrée e Guinle (HUGG) de janeiro de 2017 a junho de 2018. Foi realizado o seguinte exame oftalmológico: anamnese, acuidade visual, motilidade ocular, reflexo pupilar, biomicroscopia, tonometria de aplanação e fundoscopia. As análises estatísticas foram realizadas pelo SPSS 20.0. Resultados: A média de idade dos 40 pacientes foi 64,7 anos (dp: 5,1) e o diagnóstico de infeção pelo HIV foi em média há 16.6 anos (dp:7). A maioria dos pacientes examinados possui visão normal (n=22; 55%) e pressão intraocular normal (entre 11 e 21 mmHg). As principais queixas dos pacientes durante a anamnese foram: embaçamento visual (50%), redução da acuidade visual (47.5%), prurido ocular (27.5%), lacrimejamento (25%) e ardência (25%). As alterações biomicroscópicas mais frequentes foram catarata (92.5%), seguida de olho seco (32.5%). Na fundoscopia encontrou-se 43,8 % de alterações da vascularização retiniana, 43.8 % de alterações relacionadas ao nervo óptico e 31,3% relacionadas ao pólo posterior da retina. Conclusão: Alterações oculares foram comuns e podem ser justificadas pela: senilidade, estado inflamatório gerado pela infecção crônica do HIV, efeitos adversos da Terapia antirretroviral prolongada e senescência biológica precoce associada a infecção do HIV.

Abstract Objectives: Identify and describe ocular changes in elderly with HIV or aids through ophthalmological examination. Evaluate the association between ocular alterations and the level of TCD4 lymphocytes, time of antiretroviral therapy, demographic characteristics and age range. Methods: Case series of 40 elderly patients with HIV infection. The study was carried out at the ophthalmology and immunology outpatient clinics of the Gaffrée and Guinle University Hospital (HUGG) from january 2017 to june 2018. The patients were attended at the ophthalmology clinic and underwent a ophthalmological exam including: anamnesis, visual acuity, ocular motility, pupillary reflex, biomicroscopy, aplanation tonometry and fundoscopy. Statistical analyses were performed using SPSS 20.0. Results: The average of the 40 patients was 64.7 years (sd: 5.1), aged between 60 and 78 years, and the average time of HIV infection was 16.6 years (sd: 7 years). Most of the patients examined had normal vision (55%) and normal intraocular pressure (between 11 and 21 mmHg). The main complaints of patients during anamnesis were visual blurring (50%), visual acuity reduction (47.5%), ocular itchiness (27.5%), tearing (25%) and burning (25%).The most frequent changes in biomicroscopy were: cataract (92.5%) and dry eye (32.5%). Funduscopy found 43.8% of retinal vascularization alterations, 43.8% of alterations related to the optic nerve and 31.3% related to retinal posterior pole. Conclusion: Ocular changes were common and can be explained by senility, inflamatory changes caused by chronic HIV infection, adverse effects of antiretroviral therapy and early biological ageing associated to HIV infection.

Diagnóstico de alteraciones oculares anatómicas y funcionales en neonatos / Anatomic and functional diagnosis of ocular abnormalities in neonates

Las alteraciones oculares pueden ser funcionales o estructurales y se originan tanto en el desarrollo embrionario como en el fetal. Algunas alteraciones son inherentes a la edad gestacional, mientras que otras se relacionan a errores innatos del metabolismo, síndromes genéticos, toxicomanías o tratamientos farmacológicos recibidos por la madre en el primer trimestre de la gestación. Material y métodos: De enero de 2000 a agosto de 2012 se realizó un estudio prospectivo, transversal, observacional y descriptivo en el que se efectuó una valoración oftalmológica de todos los neonatos hospitalizados en la Unidad de Terapia Intensiva y en la Unidad de Cuidados Intermedios del recién nacido. Los niños del programa de seguimiento pediátrico también fueron evaluados. Las variables maternas medidas fueron: edad, patología endocrinológica y adicciones. Las variables neonatales fueron: sexo, edad gestacional al nacer y tipo de alteración ocular. Se utilizó estadística descriptiva. Resultados: Se estudiaron 4,583 pacientes hospitalizados y 7,815 ambulatorios. Se identificaron 179 (1.4%) niños con malformaciones oculares; 33 presentaron diversos síndromes que incluían malformaciones oculares asociadas. Hubo 93 hijos de madre diabética, 24 hijos de madres con alguna adicción y 29 hijos de madres adolescentes. El intervalo de la edad gestacional al nacer fue de 24 a 40 semanas. Conclusiones: Las anormalidades oculares en hijos de madres con DM o toxicomanías fueron más frecuentes, y se presentaron de manera única o formando parte de alteraciones congénitas múltiples.

Ocular disorders are anatomical or functional, and can appeared since embryo development or fetal stage, and be present at born. Some ocular abnormalities are related with gestacional age, while others are due to inborn metabolic errors, genetic syndromes, drug abuse or pharmacologic treatment in the mother. Methods: From January 2000 to August 2012, a prospective, transversal, observational and descriptive study was performed. An ophthalmological evaluation was made to all neonates hospitalized at the Neonatal Intensive and Intermediate Unit Care. Ambulatory infants of the follow up pediatric program also were evaluated. Maternal variables evaluated were: age, endocrine pathology, and addictions. Neonatal variables were sex, gestacional age at born, and type of ocular alteration. Descriptive statistic was done. Results: A total of 4,583 hospitalized patients and 7,815 ambulatory infants were under ophthalmological evaluation. An ocular abnormality was identified in 179 (1.4%) newborns, 33 patients had a syndrome which included ocular problems, 93 had a diabetic mother, 24 were born from addicted mother and 29 of a teen mom. The gestacional age at born range from 24 to 40 weeks. Conclusions: In this study sons of diabetic and addicted mothers seem to present more often congenital ocular malformations.

Histopathological findings and detection of parasites in the eyes of dogs infected naturally with Leishmania chagasi / Achados histopatológicos e detecção de parasitas nos olhos de cães infectados por Leishmania chagasi

The objective of the present study was to investigate the histopathological alterations and detection of parasites that occur in the eyes of dogs naturally infected with Leishmania chagasi. The eyes of 25 dogs with a positive parasitological and serological exam for L. chagasi were submitted to routine ophthalmic examination. Fragments were obtained from the eyeball and were analyzed by immunohistochemistry and histopathology. Among the structures studied, the conjunctiva of the third eyelid was the tissue most frequently stained for L. chagasi. Histopathological analysis revealed a predominantly mononuclear inflammatory infiltrate whose intensity ranged from discrete to intense in the various ocular structures. Vascular congestion and perivasculitis were also observed. The histopathological alterations that occur in the eyeball of dogs with visceral leishmaniasis might be related to the presence of antibodies.

O objetivo deste trabalho foi estudar as alterações histopatológicas e a detecção do parasito nos olhos de cães naturalmente infectados por Leishmania chagasi. Utilizaram-se os olhos de 25 cães com exame parasitológico e sorológico positivo para Leishmania chagasi. Os animais foram submetidos à semiotécnica oftálmica rotineira. Fragmentos do globo ocular foram coletados e destinados à imunoistoquímica e histopatologia. Entre as estruturas avaliadas, a conjuntiva da terceira pálpebra foi a que mais demonstrou imunomarcação da Leishmania chagasi. Na avaliação histopatológica, foi observado predominantemente infiltrado inflamatório mononuclear, variando de discreto a intenso nas diversas estruturas oculares. Congestão vascular e perivasculite também foram observadas. As alterações histopatológicas do bulbo do olho em cães com leishmaniose visceral podem estar relacionadas à presença do anticorpo.

Histopathological findings and detection of parasites in the eyes of dogs infected naturally with Leishmania chagasi

The objective of the present study was to investigate the histopathological alterations and detection of parasites that occur in the eyes of dogs naturally infected with Leishmania chagasi. The eyes of 25 dogs with a positive parasitological and serological exam for L. chagasi were submitted to routine ophthalmic examination. Fragments were obtained from the eyeball and were analyzed by immunohistochemistry and histopathology. Among the structures studied, the conjunctiva of the third eyelid was the tissue most frequently stained for L. chagasi. Histopathological analysis revealed a predominantly mononuclear inflammatory infiltrate whose intensity ranged from discrete to intense in the various ocular structures. Vascular congestion and perivasculitis were also observed. The histopathological alterations that occur in the eyeball of dogs with visceral leishmaniasis might be related to the presence of antibodies.

O objetivo deste trabalho foi estudar as alterações histopatológicas e a detecção do parasito nos olhos de cães naturalmente infectados por Leishmania chagasi. Utilizaram-se os olhos de 25 cães com exame parasitológico e sorológico positivo para Leishmania chagasi. Os animais foram submetidos à semiotécnica oftálmica rotineira. Fragmentos do globo ocular foram coletados e destinados à imunoistoquímica e histopatologia. Entre as estruturas avaliadas, a conjuntiva da terceira pálpebra foi a que mais demonstrou imunomarcação da Leishmania chagasi. Na avaliação histopatológica, foi observado predominantemente infiltrado inflamatório mononuclear, variando de discreto a intenso nas diversas estruturas oculares. Congestão vascular e perivasculite também foram observadas. As alterações histopatológicas do bulbo do olho em cães com leishmaniose visceral podem estar relacionadas à presença do anticorpo.

Histopathological findings and detection of parasites in the eyes of dogs infected naturally with Leishmania chagasi

The objective of the present study was to investigate the histopathological alterations and detection of parasites that occur in the eyes of dogs naturally infected with Leishmania chagasi. The eyes of 25 dogs with a positive parasitological and serological exam for L. chagasi were submitted to routine ophthalmic examination. Fragments were obtained from the eyeball and were analyzed by immunohistochemistry and histopathology. Among the structures studied, the conjunctiva of the third eyelid was the tissue most frequently stained for L. chagasi. Histopathological analysis revealed a predominantly mononuclear inflammatory infiltrate whose intensity ranged from discrete to intense in the various ocular structures. Vascular congestion and perivasculitis were also observed. The histopathological alterations that occur in the eyeball of dogs with visceral leishmaniasis might be related to the presence of antibodies.

O objetivo deste trabalho foi estudar as alterações histopatológicas e a detecção do parasito nos olhos de cães naturalmente infectados por Leishmania chagasi. Utilizaram-se os olhos de 25 cães com exame parasitológico e sorológico positivo para Leishmania chagasi. Os animais foram submetidos à semiotécnica oftálmica rotineira. Fragmentos do globo ocular foram coletados e destinados à imunoistoquímica e histopatologia. Entre as estruturas avaliadas, a conjuntiva da terceira pálpebra foi a que mais demonstrou imunomarcação da Leishmania chagasi. Na avaliação histopatológica, foi observado predominantemente infiltrado inflamatório mononuclear, variando de discreto a intenso nas diversas estruturas oculares. Congestão vascular e perivasculite também foram observadas. As alterações histopatológicas do bulbo do olho em cães com leishmaniose visceral podem estar relacionadas à presença do anticorpo.

Histopathological findings and detection of parasites in the eyes of dogs infected naturally with Leishmania chagasi

The objective of the present study was to investigate the histopathological alterations and detection of parasites that occur in the eyes of dogs naturally infected with Leishmania chagasi. The eyes of 25 dogs with a positive parasitological and serological exam for L. chagasi were submitted to routine ophthalmic examination. Fragments were obtained from the eyeball and were analyzed by immunohistochemistry and histopathology. Among the structures studied, the conjunctiva of the third eyelid was the tissue most frequently stained for L. chagasi. Histopathological analysis revealed a predominantly mononuclear inflammatory infiltrate whose intensity ranged from discrete to intense in the various ocular structures. Vascular congestion and perivasculitis were also observed. The histopathological alterations that occur in the eyeball of dogs with visceral leishmaniasis might be related to the presence of antibodies.

O objetivo deste trabalho foi estudar as alterações histopatológicas e a detecção do parasito nos olhos de cães naturalmente infectados por Leishmania chagasi. Utilizaram-se os olhos de 25 cães com exame parasitológico e sorológico positivo para Leishmania chagasi. Os animais foram submetidos à semiotécnica oftálmica rotineira. Fragmentos do globo ocular foram coletados e destinados à imunoistoquímica e histopatologia. Entre as estruturas avaliadas, a conjuntiva da terceira pálpebra foi a que mais demonstrou imunomarcação da Leishmania chagasi. Na avaliação histopatológica, foi observado predominantemente infiltrado inflamatório mononuclear, variando de discreto a intenso nas diversas estruturas oculares. Congestão vascular e perivasculite também foram observadas. As alterações histopatológicas do bulbo do olho em cães com leishmaniose visceral podem estar relacionadas à presença do anticorpo.