Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa.

Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.

Novel inflammatory cytokines (IL-36, 37, 38) in the aqueous humor from patients with chronic primary angle closure glaucoma.

Glaucoma eventually leads to optic nerve damage and vision loss without medical intervention. More than 50% of glaucoma caused blindness are attributed to primary angle closure glaucoma, particularly in Asians. It is reported that immune inflammation is involved in the progress of glaucoma. Increased inflammation cytokines are detected in the aqueous humor of chronic primary angle closure glaucoma (CPACG). IL-36, IL-37 and IL-38, are novel cytokines and are involved in many inflammatory diseases, including inflammatory bowel diseases and acute anterior uveitis, but the possible contributing role in the pathogenesis of CPACG is unclear. In our current study, increased IL-36, IL-37 and IL-38 were detected in the aqueous humor of CPACG compared with age-related cataract (ARC). Furthermore, a significant correlation was detected between mean deviation of visual field (MDVF) of CPACG and IL-36, IL-37 or IL-38, respectively. Our data suggest IL-36, IL-37 and IL-38 might contribute to the immunological mediated pathogenesis of CPACG, despite the eye being an immune-privileged organ under normal conditions. The precise underlying mechanism of these cytokines during the development of CPACG remains to be explored. Our findings may be useful in therapeutic targeting of specific pathology.

The genome of the miiuy croaker reveals well-developed innate immune and sensory systems.

The miiuy croaker, Miichthys miiuy, is a representative Sciaenidae known for its exceptionally large otoliths. This species mainly inhabits turbid aquatic environments with mud to sandy mud bottoms. However, the characteristics of the immune system of this organism and its specific aquatic environment adaptations are poorly understood. Thus, we present a high-quality draft genome of miiuy croaker. The expansions of several gene families which are critical for the fish innate immune system were identified. Compared with the genomes of other fishes, some changes have occurred in the miiuy croaker sensory system including modification of vision and expansion of taste and olfaction receptors. These changes allow miiuy croaker to adapt to the environment during the long-term natural selection. The genome of miiuy croaker may elucidate its relatively well-developed immune defense and provide an adaptation model of the species thriving in turbid deep aquatic environments.

Visual development in primates: Neural mechanisms and critical periods.

Despite many decades of research into the development of visual cortex, it remains unclear what neural processes set limitations on the development of visual function and define its vulnerability to abnormal visual experience. This selected review examines the development of visual function and its neural correlates, and highlights the fact that in most cases receptive field properties of infant neurons are substantially more mature than infant visual function. One exception is temporal resolution, which can be accounted for by resolution of neurons at the level of the lateral geniculate nucleus (LGN). In terms of spatial vision, properties of single neurons alone are not sufficient to account for visual development. Different visual functions develop over different time courses. Their onset may be limited by the existence of neural response properties that support a given perceptual ability, but the subsequent time course of maturation to adult levels remains unexplained. Several examples are offered suggesting that taking account of weak signaling by infant neurons, correlated firing, and pooled responses of populations of neurons brings us closer to an understanding of the relationship between neural and behavioral development.

Is visual function affected in severe ocular allergies?

PURPOSE OF REVIEW: The purpose of the present review is to provide an overview on the clinical features and long-term complications of severe ocular allergies, with a special focus on the corneal involvement observed in these diseases, which may impair vision permanently. Furthermore, different treatment options are discussed based on the sight-threatening effects of corticosteroid use. RECENT FINDINGS: Recent data on the demographics, clinical and immunologic features of vernal and atopic keratoconjunctivitis are presented and discussed, and the evidence of a lack of literature addressing the issue of visual outcome in allergic diseases is underlined. The efficacy and possible long-term complications of their treatments are described, including visual impairment. SUMMARY: Diagnosis and treatment of patients with severe ocular allergy is a challenge for ophthalmologists due to the long-term corneal complications and the potential side-effects of topical corticosteroids that may induce cataract formation and glaucoma, and impair vision permanently. The review describes old and new concepts of management and possible complications such as severe, vision-threatening forms of allergic ocular disease. An update on their management and long-term complications may help clinicians to establish a common agreement on treatment options and researchers to design future studies based on similar outcomes, including visual acuity.

Ocular surface molecule after transconjunctival vitrectomy.

AIM: To evaluate ocular surface molecules after transconjunctival pars plana vitrectomy (PPV). METHODS: A total of 28 eyes of 28 patients who received PPV were examined. Tears (10µl) were collected before and after 20-gauge PPV or 23-gauge PPV. The concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70 and tumour necrosis factor (TNF)-α were measured. The concentrations of each cytokine before and after surgery were compared. The change ratios of each cytokine (post-/presurgery) between 20-gauge and 23-gauge PPV were compared. RESULTS: IL-1ß, IL-6, IL-8 increased after PPV (Wilcoxon rank sum test; IL-1 ß, p=0.009; IL-6, p<0.001; IL-8, p<0.001), while the other cytokines did not. Among them, only IL-8 increased significantly in 20-gauge PPV than in 23-gauge PPV (p=0.01, Mann-Whitney U test). Multivariate analysis showed that 20-gauge PPV was a significant factor behind the increase in postoperative IL-8 (OR 5.21, 95% CI (1.46 to 18.55), p=0.018), but surgical time and simultaneous cataract surgery were not significant factors. CONCLUSIONS: The increase in inflammatory cytokine IL-8 in tear was significantly less after 23-gauge PPV than 20-gauge PPV, indicating that transconjunctival PPV is less invasive from the viewpoint of the ocular surface molecular biology. This information may be important when deciding the method of PPV.

Veinticinco años de la Unidad de Neuro-oftalmología del Hospital Vargas de Caracas (1980-2005): apuntes para una biografía / Twenty five years of the Neuro-ophtalmologic Unit in the Vargas Hospital in Caracas (1980-2005)

Con la Unidad de Neuro-oftalmología del Hospital Vargas de Caracas se inicia en Venezuela el estudio de condiciones que afectan el órgano de la visión y sus relaciones con el sistema nervioso central. Fundada en 1980 con una idea asistencial-docente, se ha mantenido activa por más de 25 años y es única en su género en el país. Ha sustentado su ser y hacer en cuatro principios fundamentales, asistecia, docencia, investigación clínica y extensión. Asiste a enfermos del hospital y procedentes de diversos centros de la capital, así como también del interior del país, mediante una consulta externa gratuita muy activa en la cual se evalúan diariamente cerca de 16 pacientes de consulta sucesiva y 4 de primera de consulta. Luego y sobre la base de una experiencia clínica, progresó hacia la docencia de posgrado recibiendo por cortos períodos cerca de 40 pasantes por año entre oftalmólogos, neurológos y neuropediatras; adicionalmente se aceptan médicos especialistas para programa de "fellowship" en Neuro-Oftalmología de un año de duración. De esta manera han egresado 32 fellows, 24 venezolanos y 8 extranjeros: 26 oftalmológos, 3 neurólogos y médicos internistas. Con base en muestras de pacientes atendidos a lo largo de los años, se realiza investigación clínica continua de problemas neuro-oftalmológicos, lo cual ha permitido evaluar y desempeñar las diferencias regionales de algunas condiciones clínicas que adoptan características diferentes a otras latitudes. Porteriormente ha extendido su influencia extramuros con asistencia de su personal a otros hospitales para dictar cursos, charlas y ejercicios clínicos con pacientes, y en congresos y cursos internacionales

The systematic study of the conditions that affect the visual organ and its relations with the central nervous system began in this country with the Neuro-Ophthalmology Unit of the Vargas Hospital in Caracas, ascribed to the Department of Clinical Medicine “B” of the “José María Vargas” Medical School, attached to the Faculty of Medicine of the Central University of Venezuela. Founded in 1980 as a teaching clinic, the unit has stayed active for more than 25 years and is unique in its field. It has maintained its place based on four fundamental principles: assistance, education, clinical research and expansion. It treats patients from the Vargas Hospital and from other centers of the country, through an active external consultation scheme, free of charge, in which close to 16 follow-up patients and 4 first-time patients are tended to daily. Subsequently, based on extensive clinical experience, the Unit progressed in to post-graduate education, receiving close to 40 residents from ophthalmology, neurology and neuro-pediatrics programs each year for short periods for direct and supervised teaching. Additionally, especialists have been accepted for a one-year “fellowship” program in Neuro-Ophthalmology. Thirty-two fellows (24 Venezuelans and 8 foreigners) have graduated from this program: 26 ophthalmologists, 3 neurologists and 4 internists, many of which will assume taching duties in their own countries. Over the years, based on a sample of treated patients, continued clinical research of neuro-ophthalmologic problems is undertaken, which has allowed the evaluation, unraveling and publishing of the regional differences of certain clinical conditions. Subsequently, with the assistance of its personnel, the Unit has expanded its influence to other hospitals as well as national and international institutions, running courses and lectures and conducting clinical exercises with patients