Advances in Retinal Tissue Engineering

Retinal degenerations cause permanent visual loss and affect millions world-wide. Current treatment strategies, such as gene therapy and anti-angiogenic drugs, merely delay disease progression. Research is underway which aims to regenerate the diseased retina by transplanting a variety of cell types, including embryonic stem cells, fetal cells, progenitor cells and induced pluripotent stem cells. Initial retinal transplantation studies injected stem and progenitor cells into the vitreous or subretinal space with the hope that these donor cells would migrate to the site of retinal degeneration, integrate within the host retina and restore functional vision. Despite promising outcomes, these studies showed that the bolus injection technique gave rise to poorly localized tissue grafts. Subsequently, retinal tissue engineers have drawn upon the success of bone, cartilage and vasculature tissue engineering by employing a polymeric tissue engineering approach. This review will describe the evolution of retinal tissue engineering to date, with particular emphasis on the types of polymers that have routinely been used in recent investigations. Further, this review will show that the field of retinal tissue engineering will require new types of materials and fabrication techniques that optimize the survival, differentiation and delivery of retinal transplant cells.Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USABoston Univ, Dept Grad Med Sci, Boston, MA 02215 USAUniversidade Federal de São Paulo, Dept Ophthalmol, BR-09210170 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, BR-09210170 São Paulo, BrazilWeb of Scienc

On the origin and persistence of praedial toponyms in central Italy

This paper recognises the origin of the current series of praedial place names, through successive transcripts, in the Roman land ownership system of republican and imperial times, experimenting with some methodological aspects of the use of digital cartographic sources. Acknowledging the widespread presence of praedial place names in modern cartography and medieval notarial sources, the research reconstitutes the history of the land ownership system, considering the landscape as “quella forma che l'uomo, nel corso ed ai fini delle sue attività produttive agricole, coscientemente e sistematicamente imprime al paesaggio naturale” [“the form that man, in the course and for the purpose of agricultural production, consciously and systematically imposes to the natural landscape”] (Sereni, 1961, p. 29). The two sets of data, morphology and toponymy, are proposed here as an antonymic dyad representing the symbolic relationship between population and territory. The research considers two case studies: the valley of the river Savio, and the territory belonging to the abbey of Subiaco in the Lazio region. After the close examination of toponyms in the Italian official map (scale 1:25,000) a list of praedial names was selected and, with a GIS, was correlated with another set of place names extracted from medieval notarial documents (IV-XII cent.). For some of these place names it was possible to track back the history of the site to the Roman praedium and in three cases to identify the Roman owner, through the analysis of literary and epigraphical sources. Starting from these three specific praedia it was therefore possible to infer the origin and the history of praedial place names in central Italy. Nevertheless, the persistence of these names until today was possible only through the medieval notarial transcriptions, showing some continuity in the land ownership system through the Middle Ages

Chorioretinal Coloboma Complications: Retinal Detachment and Choroidal Neovascular Membrane

PURPOSE: To report the chorioretinal coloboma, and its association with increased risk of retinal detachment (RD) and choroidal neovascularization (CNV). METHODS: This retrospective case series included eyes with chorioretinal coloboma diagnosed between 1995 and 2014 with a focus on RD and CNV as related complications. Cases of CNV were managed with laser photocoagulation or intravitreal injection of bevacizumab. For eyes with CNV, therapeutic success was defined as resolution of the subretinal hemorrhage on fundus examination and resolution of the subretinal and intraretinal fluid on optical coherence tomography (OCT). For eyes with RD, anatomic success following surgical intervention was defined as attachment of the retina at the last follow-up visit. RESULTS: Fifty-one eyes of 31 patients with chorioretinal coloboma were identified for review. Bilateral chorioretinal coloboma was present in 64.5% of subjects. RD developed in 15 eyes (29.4%). Among 15 eyes with RD, 4 eyes (27%) had retinal breaks identified within the coloboma, 5 eyes (33%) had retinal breaks outside the coloboma, 2 eyes (13%) showed retinal breaks both inside and outside the coloboma, and in 4 eyes (27%) the causative retinal break was not localized. The overall rate of anatomic success after RD repair was 85.7%. CNV developed in 7 eyes (13.7%) and was located along the margin of the coloboma in all cases. CNV was bilateral in 2 of the 5 affected individuals (40%). CONCLUSION: RD and CNV were present in a high percentage of eyes with chorioretinal coloboma in these series. The frequent finding of retinal breaks outside the coloboma bed suggests that vitreoretinal interface abnormalities may play a role in development of RD in these eyes

Lifespan extension in female mice by early, transient exposure to adult female olfactory cues

Several previous lines of research have suggested, indirectly, that mouse lifespan is particularly susceptible to endocrine or nutritional signals in the first few weeks of life, as tested by manipulations of litter size, growth hormone levels, or mutations with effects specifically on early-life growth rate. The pace of early development in mice can also be influenced by exposure of nursing and weanling mice to olfactory cues. In particular, odors of same-sex adult mice can in some circumstances delay maturation. We hypothesized that olfactory information might also have a sex-specific effect on lifespan, and we show here that the lifespan of female mice can be increased significantly by odors from adult females administered transiently, that is from 3 days until 60 days of age. Female lifespan was not modified by male odors, nor was male lifespan susceptible to odors from adults of either sex. Conditional deletion of the G protein Gαo in the olfactory system, which leads to impaired accessory olfactory system function and blunted reproductive priming responses to male odors in females, did not modify the effect of female odors on female lifespan. Our data provide support for the idea that very young mice are susceptible to influences that can have long-lasting effects on health maintenance in later life, and provide a potential example of lifespan extension by olfactory cues in mice

BTDAzo: A Photoswitchable TRPC5 Channel Activator

Photoswitchable reagents can be powerful tools for high-precision biological control. TRPC5 is a Ca2+-permeable cation channel with distinct tissue-specific roles, from synaptic function to hormone regulation. Reagents giving spatiotemporally-resolved control over TRPC5 activity may be key to understanding and harnessing its biology. Here we develop the first photoswitchable TRPC5-modulator, BTDAzo, to address this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5-based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with strong two-colour photoswitching. BTDAzo ' s ability to control TRPC5 across relevant channel biology settings makes it suitable for a range of dynamically reversible photoswitching studies in TRP channel biology, with the aim to decipher the various biological roles of this centrally important ion channel

Horizontal Diplopia and Left Side Cranial Nerve Palsies

Diplopia; PtosisA 22-year old patient with horizontal diplopia. Previous history significant for central head pain.Pupils: 5 mm OD, 3 mm OS; Ophthalmoplegia; Bilateral PtosisCTDiplopiaN/AN/

Familial Exudative Vitreoretinopathy

Ailevi eksudatif vitreoretinopati (AEVR), özellikle çocukluk çağında görme kaybına yol açan kalıtımsal bir hastalıktır. Hastalığa, NDP, FZD4, LRP5 ve TSPAN12 genlerinde mutasyonun neden olduğu gösterilmiştir. AEVR için X'e bağlı resesif, otozomal dominant ve otozomal resesif kalıtım bildirilmiştir. Bununla birlikte, hastalığın hem genotipik, hem de fenotipik özellikleri değişkenlik göstermektedir. Hastalığa neden olan yeni mutasyonlar da bildirilmektedir. Perifer retinanın avasküler olması, hastalığın ilk ve en belirgin bulgusudur. Hastalık ilerledikçe, genotipik özelliklere de bağlı olarak, retinada neovaskülarizayon, subretinal eksudasyon, kısmi veya total retina dekolmanı meydana gelir. Erken tanı ve lazer fotokoagülasyon ve anti-VEGF enjeksiyonlarını içeren dikkatli takip ile görme kaybı önlenebilir. Retina dekolmanı meydana geldiğinde pars plana vitrektomi, tek başına veya skleral çökertme ile birlikte uygulanır. Sessiz bulguları olan asemptomatik aile bireylerinin tespiti önemlidir. Floresein anjiyografi ile kombine geniş açı görüntüleme sistemleri önemli yarar sağlar. Ayırıcı tanıda Norrie hastalığı, premature retinopatisi ve Coat's hastalığı düşünülmelidirFamilial exudative vitreoretinopathy (FEVR) is a hereditary disease associated with visual loss, particularly in the pediatric group. Mutations in the NDP, FZD4, LRP5, and TSPAN12 genes have been shown to contribute to FEVR. FEVR has been reported to have X-linked recessive, autosomal dominant, and autosomal recessive inheritances. However, both the genotypic and phenotypic features are variable. Novel mutations contributing to the disease have been reported. The earliest and the most prominent finding of the disease is avascularity in the peripheral retina. As the disease progresses, retinal neovascularization, subretinal exudation, partial and total retinal detachment may occur, which may be associated with certain mutations. With early diagnosis and prompt management visual loss can be prevented with laser photocoagulation and anti-VEGF injections. In case of retinal detachment, pars plana vitrectomy alone or combined with scleral buckling should be considered. Identifying asymptomatic family members with various degrees of insidious findings is of certain importance. Wide-field imaging with fluorescein angiography is crucial in the management of this disease. The differential diagnosis includes other pediatric vitreoretinopathies such as Norrie disease, retinopathy of prematurity, and Coats’ diseas

A Novel Approach to Understanding Pathogenesis and Treatment of Capillary Dropout in Retinal Vascular Diseases.

Capillary dropout is a common sequela of endothelial cell dysfunction that underlies the pathology of multiple retinal vascular diseases, including familial exudative vitreoretinopathy (FEVR). Wide-field fluorescein angiography allowed for identification of areas of capillary inflammatory changes and late-phase angiographic posterior and peripheral vascular leakage (LAPPEL). We propose LAPPEL as a precursor in pathogenesis of capillary dropout and a marker of endothelial cell inflammation in the retina. The authors describe a case of FEVR with significant macular edema associated with LAPPEL, which was successfully treated with topical and intravitreal steroids. The implication for disease mechanism and potential future treatment applications are also discussed