Spaceflight Effects and Molecular Responses in the Mouse Eye: Observations After Shuttle Mission STS-133

Microgravity-induced cephalad fluid shift and radiation exposure are some of the stressors seen in space exploration. Ocular changes leading to visual impairment in astronauts are of occupational health relevance. Therefore, we analyzed the effects of space flight in the eyes of mice. Six mice were assigned to Flight (FLT), Animal enclosure Module (AEM), or vivarium (VIV) group, respectively. Mice were sacrificed at 1, 5 or 7 days after landing from space. One eye was used for histological and immunohistoche-mistry analysis and the other eye for gene expression profiling. 8-OHdG and caspase-3 immunoreactivity were increased in the retina in FLT samples at return(R+1) compared to AEM/VIV groups, and decreased at day 7 (R+7). beta-amyloid was seen in the nerve fibers at the post-laminar region of the optic nerve in the flight samples (R+7). In addition, oxidative and cellular stress response genes were upregulated in the retina of FLT samples upon landing, and decreased by R+7. According to the results, a reversible molecular damage may occur in the retina of mice exposed to spaceflight followed by protective cellular response

Toxicidade intravítrea da rapamicina em olhos de coelhos

PURPOSE: To evaluate retinal toxicity of varying doses of rapamycin when injected intravitreally in rabbits. Rapamycin is a potent immunosuppressive agent with significant antitumor and antiangiogenic properties, clinically approved for prevention of organ transplant rejection. METHODS: Twelve New Zealand albino rabbits were divided into four groups. Four different doses of rapamycin were prepared in 0.1 ml: 20 µg, 50 µg, 200 µg, and 1000 µg. Each concentration was injected in one eye of three rabbits, and 0.1 ml volume of sterile BSS was injected into the contralateral eye of the three rabbits. Slit-lamp and fundoscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, and toxicity. A baseline ERG was performed before drug treatment and at day 14, after which the rabbits were euthanized. Histology of the enucleated eyes was studied to look for retinal toxicity. RESULTS: ERG results showed some decrease in scotopic response; however this was not dose related. ERG results were normal at 20 µg. Histological results showed no retinal toxicity in all groups. CONCLUSION: Although ERG changes were identified at dosages between 50-1000 µg, the histology of all groups up to 1000 µg did not show any discernable abnormalities.OBJETIVO: Avaliar a toxicidade da injeção intravítrea de diferentes doses de rapamicina para a retina de coelhos. Rapamicina é uma potente droga imunossupressora aprovada clinicamente para a prevenção da rejeição de transplantes de orgãos. MÉTODOS: Doze coelhos albinos da Nova Zelândia foram usados neste estudo. Foram divididos em quatro grupos. Quatro diferentes doses de rapamicina foram preparadas nas seguintes concentrações: 20 µg, 50 µg, 200 µg, 1000 µg. Foram realizadas injeções intravítreas de 0,1 ml de cada concentração em um olho de três coelhos e 0,1 ml de solução salina foi injetada no olho contralateral de cada coelho. Foram realizadas biomicroscopia e fundoscopia e observamos sinais de inflamação, infecção ou toxicidade durante duas semanas. Fizemos um ERG antes do tratamento e outro 14 dias depois da injeção intravítrea. Os animais foram sacrificados, fizemos a enucleação dos olhos e preparamos o tecido para a avaliação histológica. RESULTADOS: Os resultados do ERG e da histologia demonstraram diminuição da resposta escotópica, entretanto essa diminuiç&atildeão foi dose dependente. A histologia foi normal em todos os grupos. CONCLUSÃO: A injeção intravítrea de rapamicina levou a alterações eletrorretinográficas nos grupos de 50-1000 µg, entretanto a histologia foi normal em todos os grupos até 1000 µg

Spaceflight and the Mouse Eye: Results from Experiments on Shuttle Missions STS-133 and STS-135

Vision alterations associated with globe flattening, chorodial folds and papilledema, shown in some crew members returning from long duration missions. Hypothesis: Ocular neuroanatomical changes observed in the VIIP syndrome are accompanied by retinal changes at the molecular and cellular level that may affect retinal health and physiology. Objective: Investigate evidence of ocular (retinal) changes associated with spaceflight: (1) histological markers of cellular death and damage (2) molecular markers of oxidative stress (3) gene expression markers of stres

Spaceflight Effects and Molecular Responses in the Mouse Eye: Observations after NASA Shuttle Mission STS-133

Background: Human space exploration implies a combination of stressors including microgravityinduced cephalad fluid shift and radiation exposure. Ocular changes in astronauts leading to visual impairment are of occupational health relevance. The effect of this complex environment on ocular morphology and function is poorly understood. Material and Methods: Mice were assigned to a Flight (FLT) group flown on shuttle mission STS133, Animal Enclosure Module (AEM), or vivarium (VIV) ground controls. Eyes were collected at 1, 5 and 7 days after landing, and were fixed for histological sectioning. The contralateral eye was used for gene expression profiling by qRT-PCR. Routine histology and immunohistochemistry using 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, glial fibrillary acidic protein (GFAP) and beta-amyloid were used to study the eyes. Results and Conclusions: 8-OHdG and caspase-3 immunoreactivity was increased in the retina in FLT samples at return from flight (R+1) compared to ground controls, and decreased at day 7 (R+7), suggesting an increase in oxidative stress and cell apoptosis. FLT mice showed evidence of retinal pigment epithelium (RPE) apoptosis possibly secondary to oxidative damage. Although attenuation of RPE has been related to retinal choroidal folds in astronauts, it is yet to be determined whether or not increased RPE apoptosis may contribute to the formation of choroidal folds or may increase the risk for other retinal pathologies, such as AMD. beta-amyloid was seen in the nerve fibers at the post-laminar region of the optic nerve in the flight samples (R+7). Deposition of beta-amyloid has a strong correlation with mechanical trauma. The coexpression of GFAP in astrocytes and oligodentrocytes in these same areas supports the possible mechanical origin probably secondary to intracranial pressure that is transmitted into the nerve, as a result of an increase in venous pressure associated to microgravity-induced cephalic fluid shift. However, there is the need to further investigate the nature of the changes through additional experimental work. Gene expression of oxidative and cellular stress response genes was unregulated in the retina of FLT samples upon landing followed by lower levels by R+7. These results suggest that reversible molecular damage occurs in the retina of mice exposed to spaceflight and that protective cellular and molecular pathways are induced in the retina in response to these changes

Optic Neuropathy in Chronic Lymphocytic Leukemia

"Central nervous system involvement in chronic lymphocytic leukemia(CLL) is rare. It may manifest with cognitive dysfunction, cerebellar signs, or cranial nerve palsies. Optic neuropathy (ON) in CLL is extremely rare with few previous reports described. Diagnosis is typically made from CSF analysis. Previous case studies have reported successful treatment with radiation or intrathecal methotrexate. We report an unusual case of CLL optic neuropathy.

Stonewalled

"We present a patient with biopsy proven calcific uremic arteriolopathy causing a bilateral anterior ischemic optic neuropathy (AION).

RecutClub.com: An open source, whole slide image-based pathology education system

Background: Our institution's pathology unknown conferences provide educational cases for our residents. However, the cases have not been previously available digitally, have not been collated for postconference review, and were not accessible to a wider audience. Our objective was to create an inexpensive whole slide image (WSI) education suite to address these limitations and improve the education of pathology trainees. Materials and Methods: We surveyed residents regarding their preference between four unique WSI systems. We then scanned weekly unknown conference cases and study set cases and uploaded them to our custom built WSI viewer located at RecutClub.com. We measured site utilization and conference participation. Results: Residents preferred our OpenLayers WSI implementation to Ventana Virtuoso, Google Maps API, and OpenSlide. Over 16 months, we uploaded 1366 cases from 77 conferences and ten study sets, occupying 793.5 GB of cloud storage. Based on resident evaluations, the interface was easy to use and demonstrated minimal latency. Residents are able to review cases from home and from their mobile devices. Worldwide, 955 unique IP addresses from 52 countries have viewed cases in our site. Conclusions: We implemented a low-cost, publicly available repository of WSI slides for resident education. Our trainees are very satisfied with the freedom to preview either the glass slides or WSI and review the WSI postconference. Both local users and worldwide users actively and repeatedly view cases in our study set

An Atypical Case of Orbital Rhabdoid Tumor

Malignant rhabdoid tumor of the orbit is rare and can present with findings similar to a glioma but portends a more aggressive course and poor prognosis. We present the case of a child with a rapidly growing orbital tumor that initially presented with findings mimicking that of an optic nerve glioma