Beneficial effects of Anadenanthera colubrina (Vell.) Brenan extract on the inflammatory and nociceptive responses in rodent models

Ethnopharmacological relevance:Anadenantheracolubrina (Vell.) Brenan,popularlyknownas “angico”, is a plantthathasbeenwidelyusedinfolkmedicineduetoitsanti-inflammatory property.Toevaluatethe pharmacological activitiesofthisplant,studieswereperformedonitsantinociceptiveandanti- inflammatoryproperties. Materials andmethods: The AEof Anadenantheracolubrina, madefromthebark,wasusedinrodentsvia oral route(p.o.),at100,200,and400mg/kginclassicalmodelsofnociception(aceticacid-induced writhing andhot-platetest)andinflammation evokedbycarrageenan(e.g.,pawedema,peritonitis,and synovitis). Results: The aceticacid-inducedabdominalwrithesinmiceweresignificantly reduced(Po0.001)by oral treatmentwiththeextract(100,200,and400mg/kg),buttheextractdidnotsignificantly increase the latencyinthenociceptivehot-platetest. Anadenantheracolubrina aqueousextractreduced significantly theedemaand,besides,diminishedthemieloperoxidaseactivity(200and400mg/kg, Po0.01).Thecarrageenan-inducedperitonitiswassignificantly reduced(Po0.05) bytheaqueous extractat100,200,and400mg/kg.Theaqueousextract(200mg/kg)reducesthesynovialleukocyte infiltration oncarrageenan-inducedsynovitisinrats(Po0.01),butfailedtosignificantly affectjoint swelling andimpairedmobility. Conclusions: Weshowforthe first timethattheanti-inflammatory andperipheralantinociceptive activities of Anadenantheracolubrina are consistent,atleastinpart,withtheuseofthisplantinpopular medicine practices.

Utilizzo dell'esame dermoscopico nella valutazione clinica e nel follow up dei nevi melanocitici in sede acrale dell'età pediatrica: studio retrospettivo osservazionale

La dermoscopia, metodica non invasiva, di pratico utilizzo e a basso costo si è affermata negli ultimi anni come valido strumento per la diagnosi e il follow up delle lesioni cutanee pigmentate e non pigmentate. La presente ricerca è stata incentrata sullo studio dermoscopico dei nevi melanocitici a localizzazione palmo-plantare, acquisiti e congeniti, in età pediatrica: a questo scopo sono state analizzate le immagini dei nevi melanocitici acrali nei pazienti visitati c/o l’ambulatorio di Dermatologia Pediatrica del Policlinico Sant’Orsola Malpighi dal 2004 al 2011 per definire i principali pattern dermoscopici rilevati ed i cambiamenti osservati durante il follow up videodermatoscopico. Nella nostra casistica di immagini dermoscopiche pediatriche abbiamo notato un cambiamento rilevante (inteso come ogni modificazione rilevata tra il pattern demoscopico osservato al baseline e i successivi follow up) nell’88,6% dei pazienti ed in particolare abbiamo osservato come in un’alta percentuale di pazienti (80%), si sia verificato un vero e proprio impallidimento del nevo melanocitico e in un paziente è stata evidenziata totale regressione dopo un periodo di tempo di 36 mesi. E’ stato interessante notare come l’impallidimento della lesione melanocitaria si sia verificata per lo più in sedi sottoposte ad una sollecitazione meccanica cronica, come la pianta del piede e le dita (di mani e piedi), facendoci ipotizzare un ruolo del traumatismo cronico nelle modificazioni che avvengono nelle neoformazioni melanocitarie dei bambini in questa sede.

Das wasserlösliche Chlorophyll-Protein (WSCP): biochemische Charakterisierung und Untersuchungen zur biologischen Funktion

Das WSCP (water-soluble chlorophyll protein) der Brassicaceen ist das einzig bekannte Chlorophyll-bindende Protein, welches keine Carotinoide bindet. Es ist ein wasserlösliches, ca. 80 kDa großes Homotetramer mit 1-4 gebundenen Chlorophyllen. Das Protein ist äußerst stabil und vermag die gebundenen Chlorophylle vor Photooxidation zu schützen. Seine Funktion in der Pflanze ist bis heute ein Rätsel und sollte in dieser Arbeit zusammen mit seinen biochemischen Eigenschaften weiter aufgeklärt werden. Es wurden Versuche durchgeführt mit nativem und rekombinantem WSCP aus Blumenkohl (BoWSCP bzw. BoWSCPhis) und aus Arabidopsis thaliana (AtWSCP bzw. AtWSCPhis). Die Expressionsausbeute von BoWSCPhis konnte verbessert werden und zusätzlich wurde die Rekonstitutionsmethode für das rekombinante WSCP optimiert, sodass das pigmentierte Protein mit hoher Ausbeute und großer Reinheit gewonnen werden konnte. Zudem wurde ein neuer WSCP-Klon hergestellt, mBoWSCPhis, der in seiner Sequenz dem maturen nativen BoWSCP entspricht und weitaus weniger Aggregationsprobleme zeigte als BoWSCPhis. Weiterführende Versuche zur Stabilität und dem Oligomerisierungsgrad von WSCP haben die neue Erkenntnis erbracht, dass die Phytolschwänze der von WSCP gebundenen Chlorophylle zwar essentiell sind für die Stabilität von WSCP-Oligomeren, nicht aber für die Oligomerisierung selbst, wie es in der Literatur bislang postuliert wurde. Zusätzlich zu ihrer außerordentlichen Hitzestabilität erwiesen sich die Chl-WSCP-Komplexe als stabil in einem breiten pH-Spektrum. AtWSCPhis besaß eine vergleichbare Stabilität, und auch das Oligomerisierungsverhalten zeigte Ähnlichkeiten zu BoWSCPhis. Im Rahmen einer Forschungskooperation mit dem Institut für Optik und Atomare Physik der TU Berlin wurden zeitaufgelöste Absorptionsspektren sowie Tieftemperatur-Fluoreszenzspektren an Chl-WSCP-Komplexen gemessen. Die Ergebnisse zeigten deutlich, dass die WSCP-gebundenen Chlorophylle excitonisch gekoppelt sind und wiesen zudem auf unterschiedliche Chl-Bindungsmodi hin. Aufgrund seines einfachen Aufbaus und seines geringen Chlorophyllgehalts hat sich WSCP bei diesen Versuchen als sehr geeignetes Modellsystem erwiesen, um Messungen zur Chlorophyllbindung mit Vorhersagen aus theoretischen Modellen zu vergleichen. Bei den Experimenten zur biologischen Funktion wurden einerseits Arabidopsis thaliana WSCP-„knock-out“-Pflanzen unter verschiedenen Bedingungen charakterisiert, andererseits wurden Experimente mit rekombinantem WSCP durchgeführt, um eine mögliche Interaktion mit anderen Proteinen zu detektieren. Die vegetativen Stadien der Mutante zeigten keinen Phänotyp; das native Arabidopsis-WSCP konnte später bei der Wildtyp-Pflanze ausschließlich in jungen Schoten lokalisiert werden, was eine Erklärung hierfür lieferte. Rekombinantes WSCP konnte Chlorophylle aus nativem LHCII entfernen, eine Interaktion mit Chlorophyllase konnte jedoch nicht nachgewiesen werden; daher konnte auch die Hypothese, WSCP sei ein Chl-Carrier beim Chl-Abbau, nicht untermauert werden. Bei den durchgeführten Enzym-Assays wurde eine geringfügige Inhibition der Cysteinprotease Papain beobachtet, aber keine Inhibition der Serinprotease Trypsin, obwohl Blumenkohl-WSCP N-proximal das Motiv der Künitz-Proteaseinhibitoren besitzt. Die Frage nach der biologischen Funktion von WSCP bleibt also weiterhin offen.

In situ melanoma of the nail unit in children: report of two cases in fair-skinned Caucasian children

Nail melanoma in children is rarely reported in the literature, and all of the published cases were diagnosed in dark-skinned phototypes or in Asians. We report two cases of in situ nail matrix melanoma presenting as longitudinal melanonychia (LM) in fair-skinned children of Italian origin. Nail plate dermatoscopy revealed a brown background with lines of irregular color, spacing, and thickness in both cases. Histopathology of the excised lesions showed melanoma in situ. Clinical, dermatoscopic, and pathological criteria that permit clear differentiation of benign melanocytic activation or proliferation from nail matrix melanoma are not established for children. The presence of a pigmented band of a single nail in a child usually represents a problem for clinicians, because the clinical and dermatoscopic features that are considered possible indicators of nail unit melanoma in adults are frequently observed in benign melanocytic hyperplasia and nevi in children. There is therefore the need to find parameters useful for clinical and dermatoscopic diagnosis in childhood nail pigmentation and to reach a consensus on management of children with a band of LM.

Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog

The objectives of this study were to establish dose-response and blood concentration-response relationships for robenacoxib, a novel nonsteroidal anti-inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)-2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra-articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX-1 and COX-2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose-related improvement in weight-bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED(50) was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti-inflammatory effects of robenacoxib were significantly superior to placebo (0.25-4 mg/kg robenacoxib) and were non-inferior to meloxicam (0.5-4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose-related inhibition of COX-2 (estimated ED(50) was 0.52 mg/kg) but no inhibition of COX-1. At a dosage of 1-2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.

Black hair follicular dysplasia in Large Münsterländer dogs: clinical, histological and ultrastructural features

Four Large Münsterländer cross-bred dogs affected with black hair follicular dysplasia (BHFD) and one unaffected control littermate were observed, and skin was sampled weekly over the first 19 weeks of life. Affected dogs were born with silvery grey hair, a consequence of melanin clumping in the hair shafts. Hair bulb melanocytes were densely pigmented, and contained abundant stage IV melanosomes but adjacent matrix keratinocytes lacked melanosomes. Melanin clumping was not prominent in epidermal melanocytes in the haired skin but occurred in the foot pads. Follicular changes progressed from bulbar clumping, clumping in the isthmus/infundibulum and finally to dysplastic hair shafts. Alopecia developed progressively in pigmented areas. Silver-grey hair, melanin clumping, accumulation of stage IV melanosomes within melanocytes and insufficient melanin transfer to adjacent keratinocytes are also classic features of human Griscelli syndrome. The underlying cause in Griscelli syndrome is a defect of melanocytic intracellular transport proteins leading to inadequate and disorganized melanosome transfer to keratinocytes with resultant melanin clumping. In view of the correlation in the phenotype, histology and ultrastructure between both disorders, a defect in intracellular melanosome transport is postulated as the pathogenic mechanism in BHFD.

[Inherited alopecia X in Pomeranians]

Four male Pomeranians that showed alopecia with an age of onset between five months and eight years were investigated.The aim of the investigation was to clarify whether the affected dogs had alopecia X and whether their symptoms might be due to a hereditary defect.The four affected dogs showed hairless patches at the root of the tail, at the back, at the limbs from the thigh to the tarsus and at the abdomen. Within the hairless patches some islets with sparse hair were present. In hairless patches the skin was dark pigmented. Besides the alopecia and hyperpigmentation no other symptoms were found according to anamnestic and clinical examination. History, clinical examinations, laboratory diagnostics, and histopathology of skin biopsies allowed the diagnosis of alopecia X in three affected male dogs.The last one of the affected dogs additionally had slightly reduced thyroid hormone levels. Based on identical symptoms and the close relatedness of all four animals, it was assumed that the fourth affected dog also had alopecia X.The available data possibly indicate a monogenic autosomal dominant inheritance, however a recessive inheritance can not be excluded at this time.

An adaptive ERG technique to measure normal and altered dark adaptation in the mouse

The time-course of dark adaptation provides valuable insights into the function and interactions between the rod and cone pathways in the retina. Here we describe a technique that uses the flash electroretinogram (ERG) response to probe the functional integrity of the cone and rod pathways during the dynamic process of dark adaptation in the mouse. Retinal sensitivity was estimated from the stimulus intensity required to maintain a 30 microV criterion b-wave response during a 40 min period of dark adaptation. When tracked in this manner, dark adaptation functions in WT mice depended upon the bleaching effects of initial background adaptation conditions. Altered dark adaptation functions, commensurate with the functional deficit were recorded in pigmented mice that lacked cone function (Gnat2 ( cplf3 )) and in WT mice injected with a toxin, sodium iodate (NaIO(3)), which targets the retinal pigment epithelium and also has downstream effects on photoreceptors. These data demonstrate that this adaptive tracking procedure measures retinal sensitivity and the contributions of the rod and/or cone pathways during dark adaptation in both WT control and mutant mice.

Novel TULP1 mutation causing leber congenital amaurosis or early onset retinal degeneration

PURPOSE: To report a large, consanguineous Algerian family affected with Leber congenital amaurosis (LCA) or early-onset retinal degeneration (EORD). METHODS: All accessible family members underwent a complete ophthalmic examination, and blood was obtained for DNA extraction. Homozygosity mapping was performed with markers flanking 12 loci associated with LCA. The 15 exons of TULP1 were sequenced. RESULTS: Seven of 30 examined family members were affected, including five with EORD and two with LCA. All patients had nystagmus, hemeralopia, mild myopia, and low visual acuity without photophobia. Fundus features were variable among EORD patients: typical spicular retinitis pigmentosa or clumped pigmented retinopathy with age-dependent macular involvement. A salt-and-pepper retinopathy with midperipheral retinal pigment epithelium (RPE) atrophy was present in the older patients with LCA, whereas the retina appeared virtually normal in the younger ones. Both scotopic and photopic electroretinograms were nondetectable. Fundus imaging revealed a perifoveal ring of increased fundus autofluorescence (FAF) in the proband, and optical coherence tomography disclosed a thinned retina, mainly due to photoreceptor loss. Linkage analysis identified a region of homozygosity on chromosome 6, region p21.3, and mutation screening revealed a novel 6-base in-frame duplication, in the TULP1 gene. CONCLUSIONS: Mutation in the TULP1 gene is a rare cause of LCA/EORD, with only 14 mutations reported so far. The observed intrafamilial phenotypic variability could be attributed to disease progression or possibly modifier alleles. This study provides the first description of FAF and quantitative reflectivity profiles in TULP1-related retinopathy.

Hip arthroscopy after previous surgical hip dislocation for femoroacetabular impingement

PURPOSE: The purpose of this study was to examine whether arthroscopic adhesiolysis can relieve symptoms of patients with persistent pain after open surgical hip dislocation for femoroacetabular impingement syndrome without osseous or cartilaginous alterations. METHODS: This study comprised 16 consecutive patients (6 men and 10 women; mean age, 33.5 years [range, 19 to 60 years]) with persistent pain without osseous or cartilaginous alterations after surgical hip dislocation for the treatment of femoroacetabular impingement. At index surgery, all patients had osteochondroplasty of the head-neck junction and resection of the acetabular rim with reattachment of the labrum in 9 cases. All patients had preoperative magnetic resonance imaging-arthrogram and were treated with arthroscopy of the hip. RESULTS: At arthroscopy, all reattached labra were stable. In the cases without preservation of the labrum at the index operation, the joint capsule was attached at the level of the acetabular rim and synovitis was noticed. All patients had adhesions between the neck of the femur and joint capsule or between the labrum and capsule. In 3 patients the arthroscopic procedure was technically limited by massive thickening of the capsule. Overall, 81% of patients (13/16) showed less pain or were pain-free. The Merle d'Aubigné score improved from 13 points preoperatively to 16 points at the last follow-up. CONCLUSIONS: Persistent pain after surgical dislocation of the hip without evidence of cartilaginous and osseous alterations could result from intra-articular adhesions. Hip arthroscopy after previous surgery can be demanding because of scarring. If the adhesions can be released, good results can be achieved. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Emphysema and secondary pneumothorax in young adults smoking cannabis

BACKGROUND: We observed a remarkable increase in the number of young patients who presented with lung emphysema and secondary spontaneous pneumothorax (SSP) at our institution for over a period of 30 months; most of them have a common history of marijuana abuse. STUDY DESIGN: Retrospective case series. METHODS: Seventeen young patients presented with spontaneous pneumothorax with bullous lung emphysema were systematically evaluated over a period of 30 months. All were regular marijuana smokers. Clinical history, chest X-ray, CT-scan, lung function test, and laboratory and histological examinations were assessed. We compared the findings of this group (group I) with the findings of non-marijuana smoking patients (group II) in the same period. The findings of this series were also compared with the findings of 75 patients presented with pneumothorax in a previous period from January 2000 till March 2002 (group III). RESULTS: In group I, there were 17 patients: the median age of the patients was 27 years (range 19-43 years), 16 males and 1 female. All were living in Switzerland. All but one smoked marijuana daily for a mean of 8.8 years and tobacco for 11.8 years. CT-scan showed multiple bullae at the apex or significant bullous emphysema with predominance in the upper lobes only in two patients. Only two patients had reduced forced first second expiratory volume (FEV1) and one reduced vital capacity (VC) below the predicted 50%. This correlated with the subjectively asymptomatic condition of the patients. All but two patients were treated by video-assisted thoracoscopic surgery (VATS) for prevention of relapsing pneumothorax. Histology showed severe lung emphysema, inflammation, and heavily pigmented macrophages. In group II, there were 85 patients: there were 78 males, the median age was 24 years (range 17-40 years), 74 patients smoked tobacco for 13.4 years but no marijuana. CT-scan in 72 patients showed only small bullae at the apex but no significant emphysema; other clinical, laboratory, and histopathological findings showed no significant difference in group I. In group III, there were 75 patients: there were 71 males and 4 females. Mean age was 25 years (range 16-46 years). Six smoked marijuana daily for a mean of 3.2 years, and 62 smoked tobacco for 14 years. CT-scan done in 59 patients showed few small bullae at the apex but no significant lung emphysema. The presence of lung emphysema on CT-scan in group I was significantly different than in groups II and III (p=0.14). No significant difference was found among all groups in the form of clinical, laboratory, and histopathological findings. CONCLUSIONS: In case of emphysema in young individuals, marijuana abuse has to be considered in the differential diagnosis. The period of marijuana smoking seems to play an important role in the development of lung emphysema. This obviously quite frequent condition in young and so far asymptomatic patients will have medical, financial, and ethical impact, as some of these patients may be severely handicapped or even become lung transplant candidates in the future.

High-resolution ultrasound confirms reduced synovial hyperplasia following rituximab treatment in rheumatoid arthritis

OBJECTIVE: To assess the response of RA patients to rituximab (RTX) treatment using a sensitive imaging technique for synovitis. METHODS: Twenty-three RA patients were treated with two 1000-mg infusions of the B-cell depleting antibody, RTX, in an observational protocol. Clinical response was assessed by the European League Against Rheumatism (EULAR) response criteria. High-resolution grey-scale and colour-coded power Doppler (PD) ultrasonography was performed at baseline and 6 months after RTX. The second to fifth MCP and PIP joints were bilaterally examined with joints in a neutral 0 position from a palmar view and scored from 0 to 3. RESULTS: Median disease activity score (DAS28) improved from 5.03 to 3.56 (P = 0.001), which corresponded to a EULAR moderate response in 11 of 23 patients and a EULAR good response in another 6 patients. Improved control of disease activity by RTX was also indicated by tapering of median daily corticosteroid doses from 10 to 5 mg, without flare ups. Mean grey-scale scores correlated with the swollen joint count at baseline (r = 0.484, P = 0.022) and month 6 (r = 0.519, P = 0.011). Mean grey-scale scores improved upon RTX from a 0.90 median (range 0.13-1.87) to 0.75 (range 0.19-1.50, P = 0.023). Frequency of PD positive joints was low (6.1%) at baseline and did not significantly change following RTX treatment. CONCLUSIONS: High-resolution grey-scale ultrasonography (US) examination confirmed reduced synovial hyperplasia, but the applied PD method displayed no significant changes. Therefore, only grey-scale US is recommended in follow-up examinations after RTX treatment.

Equine pastern vasculitis: a clinical and histopathological study.

Equine pastern vasculitis is clinically challenging and the underlying aetiopathogenesis is unclear. The aims of this retrospective study were to establish histopathological criteria for pastern vasculitis, to look for an underlying cause, to investigate whether the histopathological lesions are associated with a distinct clinical picture, to assess if and how the clinical picture varies, and to determine the treatment response. Skin biopsies and clinical data from 20 horses with a diagnosis of vasculitis of the distal extremities were investigated and histology was compared to biopsies from healthy horses. It was concluded that intramural inflammatory cells, leukocytoclasia with nuclear dust, thickening and oedema of the vessel walls, and microhaemorrhages are highly specific histological findings in equine pastern vasculitis. Based on the feedback from the clinicians, the lesions were mostly seen on the lateral and medial aspects of un-pigmented legs. Lesions in white skin were characterised by exudation and crusts, whereas those in pigmented skin were alopecic and characterised by scaling. The response to treatment was poor and the prognosis guarded. No association was found between any of the histopathological findings and a distinct clinical picture. An underlying cause of equine pastern vasculitis could not be identified. Considering the large number of confounding factors, the causative agents are difficult to identify, but may involve drugs or a hypersensitivity reactions to yet unknown antigens.

Dental Caries and Microbiota in Children with Black Stain and Non-discoloured Dental Plaque

Aim: We aimed to assess caries experience and microbiota in systemically healthy children with black stain (BS) and non-discoloured plaque. Methods: Forty-six children with BS and 47 counterparts with non-discoloured plaque aged 7.9 ± 1.3 years were clinically examined. Dental caries was scored using WHO criteria. Samples of BS and non-discoloured dental plaque were collected from tooth surfaces. The DNA of the samples was extracted and real-time PCR was performed to determine the total number of bacteria and the species Streptococcus mutans, S. sobrinus, Lactobacillus sp., Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum. Results: Children with BS had lower DMFT (p = 0.013), lower DT values (p = 0.005) and a tendency to lower caries prevalence (p = 0.061) than children with non-discoloured plaque. Plaque samples of the BS group contained higher numbers of A. naeslundii (p = 0.005) and lower numbers of F. nucleatum (p = 0.001) and Lactobacillus sp. (p = 0.001) compared to the non-discoloured plaque samples of the control group. Comparing the children with BS and non-discoloured plaque, higher counts for A. naeslundii (p = 0.013) were observed in caries-free children with BS while in caries-affected children with BS, lower counts of F. nucleatum (p = 0.007) were found. Counts of Lactobacillus sp. were higher in non-discoloured plaque samples than in BS of caries-free and caries-affected children. Conclusion: Results suggest that the different microbial composition of BS might be associated with the lower caries experience in affected subjects. The role of black-pigmented bacteria associated with periodontitis needs further studies. © 2013 S. Karger AG, Basel.

Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate.

Retinal degeneration causes vision impairment and blindness in humans. If one day we are to harness the potential of stem cell-based cell replacement therapies to treat these conditions, it is imperative that we better understand normal retina development. Currently, the genes and mechanisms that regulate the specification of the neuroretina during vertebrate eye development remain unknown. Here, we identify sine oculis-related homeobox 3 (Six3) as a crucial player in this process in mice. In Six3 conditional-mutant mouse embryos, specification of the neuroretina was abrogated, but that of the retinal pigmented epithelium was normal. Conditional deletion of Six3 did not affect the initial development of the optic vesicle but did arrest subsequent neuroretina specification. Ectopic rostral expansion of Wnt8b expression was the major response to Six3 deletion and the leading cause for the specific lack of neuroretina, as ectopic Wnt8b expression in transgenic embryos was sufficient to suppress neuroretina specification. Using chromatin immunoprecipitation assays, we identified Six3-responsive elements in the Wnt8b locus and demonstrated that Six3 directly repressed Wnt8b expression in vivo. Our findings provide a molecular framework to the program leading to neuroretina differentiation and may be relevant for the development of novel strategies aimed at characterizing and eventually treating different abnormalities in eye formation.