Survival and remodeling of melanopsin cells during retinal dystrophy

The melanopsin positive, intrinsically photosensitive retinal ganglion cells (ipRGCs) of the inner retina have been shown to send wide-ranging projections throughout the brain. To investigate the response of this important cell type during retinal dystrophy, we use the Royal College of Surgeons (RCS) dystrophic rat, a major model of retinal degeneration. We find that ipRGCs exhibit a distinctive molecular profile that remains unaltered during early stages of outer retinal pathology (15 weeks of age). In particular, these cells express betaIII tubulin, alpha-acetylated tubulin, and microtubule-associated proteins (MAPs), while remaining negative for other RGC markers such as neurofilaments, calretinin, and parvalbumin. By 14 months of age, melanopsin positive fibers invade ectopic locations in the dystrophic retina and ipRGC axons/dendrites become distorted (a process that may involve vascular remodeling). The morphological abnormalities in melanopsin processes are associated with elevated immunoreactivity for MAP1b and a reduction in alpha-acetylated tubulin. Quantification of ipRGCs in whole mounts reveals reduced melanopsin cell number with increasing age. Focusing on the retinal periphery, we find a significant decline in melanopsin cell density contrasted by a stability of melanopsin positive processes. In addition to these findings, we describe for the first time, a distinct plexus of melanopsin processes in the far peripheral retina, a structure that is coincident with a short wavelength opsin cone-enriched rim. We conclude that some ipRGCs are lost in RCS dystrophic rats as the disease progresses and that this loss may involve vascular remodeling. However, a significant number of melanopsin positive cells survive into advanced stages of retinal degeneration and show indications of remodeling in response to pathology. Our findings underline the importance of early intervention in human retinal disease in order to preserve integrity of the inner retinal photoreceptive network.     

Mucocutaneous candidiasis, anergy and a plasma inhibitor of cellular immunity: reversal after amphotericin B therapy

A patient with chronic mucocutaneous candidiasis and cutaneous anergy has been studied and found to have a circulating plasma factor capable of quenching in vitro lymphocyte responses of leucocytes of clinically well donors to monilia and other specific mitogenic stimulants. After instituting systemic amphotericin B therapy, the patient exhibited rapid clearing of cutaneous and mucosal lesions and the plasma inhibitor was no longer demonstrable. Loss of the plasma inhibitor was followed by appearance of strong cutaneous hypersensitivity and in vitro leucocyte responses to Candida albicans and streptococcal products. These clinical immunologic studies have pointed meaning in relationship to current views regarding immunologic reconstitution vis-à-vis systemic antifungal therapy in treatment of chronic candidiasis.     

Ethnomedicinal practices and medicinal plant knowledge of the Yuracarés and Trinitarios from Indigenous Territory and National Park Isiboro-Sécure, Bolivian Amazon

Aim of the study

We investigated the ethnomedical practices and knowledge of medicinal plant and fungus species of contemporary Yuracaré and Trinitario ethnic groups from Indigenous Territory and National Park Isiboro-Sécure (TIPNIS), located in the Bolivian Amazon region.Our aim was to identify the culturally most significant medicinal plant families, growth forms and species, as well as to assess the current state of knowledge regarding the bioactivity of the most important species, based on available literature data.

Materials and methods

Medicinal plant and fungus species were inventoried during homegarden and swidden sampling, walk-in-the-woods and transect sampling. Data on medicinal uses were obtained from 12 Yuracaré and 14 Trinitario participants.

Results

We commence by providing a brief overview of Yuracaré and Trinitario ethnomedical systems, highlighting the important shamanistic component of particularly Trinitario traditional medicine. The rest of the paper is dedicated to an analysis and discussion based on the 349 inventoried medicinal plant and fungus species. Contingency table and binomial analyses of medicinal plants used versus the total number of inventoried species per family showed that several plant families are significantly over (Piperaceae, Araceae, Solanaceae, Asteraceae and Siparunaceae) and underused (Chrysobalanaceae, Sapotaceae, Lauraceae, Celastraceae and Annonaceae) in traditional medicine in TIPNIS. Also herbaceous plants are significantly overrepresented in the medicinal plant inventory, which is in line with relevant literature. Our ranking of medicinal species according to cultural significance is based on the Quality Use Agreement Value (QUAV) index we developed and presented in a previous paper. Results indicate that the QUAV index's property to mainly select species that combine multiple ethnomedical uses with high informant consensus, justifies its use as a measure of cultural significance of medicinal plants in TIPNIS. Results of a literature search suggest, on the other hand, that the QUAV_s score of a species could also be indicative of its bioactivity.

Conclusions

In addition to the QUAV index's value as a tool for assessing the cultural significance of medicinal species, it might also be useful to identify species with a higher likeliness of being bioactive.     

Dopamine neurones form a discrete plexus with melanopsin cells in normal and degenerating retina

In addition to rods and cones of the outer retina, a third class of photoreceptive cell has recently been described in the inner retina of mammals. These intrinsically photosensitive retinal ganglion cells (ipRGCs) have been shown to relay luminance information to the mammalian brain. In addition to their intrinsic photosensitivity, the function of ipRGCs may also be modulated by signals from within the retina itself. Such signals may emanate from classical photoreceptors in the outer retina or from the circadian activity of adjacent inner retinal neurones. Prime candidates for the latter are the retinal dopamine neurones which ramify at the border of the inner plexiform and inner nuclear layers. In order to investigate the nature of any interaction between dopamine and ipRGC populations in normal retina and to assess the impact of outer retinal degeneration on this interrelationship, we examined the retinae of normal and RCS dystrophic rats. We report a direct interaction between the dendrites of ipRGCs and dopaminergic neurones which is conserved across species. Triple immunolabelling using synaptic markers provides evidence for the unidirectionality of information transfer between the two cell types, with processes of ipRGCs being directly adjacent to sites of dopamine release. This fundamental architectural feature of the mammalian retina appears resistant to degeneration of classical photoreceptors and may provide the anatomical substrate by which dopamine cells influence the physiology of central circadian targets in the brain.     

Eel visual pigments revisited: the fate of retinal cones during metamorphosis

During their complex life history, anguilliform eels go through a major metamorphosis when developing from a fresh water yellow eel into a deep-sea silver eel. In addition to major changes in body morphology, the visual system also adapts from a fresh water teleost duplex retina with rods and cones, to a specialized deep-sea retina containing only rods. The history of the rods is well documented with an initial switch from a porphyropsin to a rhodopsin (P523(2) to P501(1)) and then a total change in gene expression with the down regulation of a "freshwater" opsin and its concomitant replacement by the expression of a typical "deep-sea" opsin (P501(1) to P482(1)). Yellow eels possess only two spectral classes of single cones, one sensitive in the green presumably expressing an RH2 opsin gene and the second sensitive in the blue expressing an SWS2 opsin gene. In immature glass eels, entering into rivers from the sea, the cones contain mixtures of rhodopsins and porphyropsins, whereas the fully freshwater yellow eels have cone pigments that are almost pure porphyropsins with peak sensitivities at about 540-545 nm and 435-440 nm, respectively. However, during the early stages of metamorphosis, the pigments switch to rhodopsins with the maximum sensitivity of the "green"-sensitive cone shifting to about 525 nm, somewhat paralleling, but preceding the change in rods. During metamorphosis, the cones are almost completely lost.     

Light-induced c-fos in melanopsin retinal ganglion cells of young and aged rodless/coneless (rd/rd cl) mice

Non‐rod, non‐cone ocular photoreceptors have been shown to mediate a range of irradiance detection tasks. The strongest candidates for these receptors are melanopsin‐positive retinal ganglion cells (RGCs). To provide a more complete understanding of these receptors in vivo, we have utilized a mouse that lacks rod and cone photoreceptors (rd/rd cl) and compared these animals to congenic wild‐types. Using real‐time polymerase chain reaction and immunohistochemistry, we address the following. (1) Is Fos expression within these RGCs driven by an input from the rods/cones or is it the product of the intrinsic photosensitivity of these neurons? We demonstrate that most Fos expression across the entire retina is due to the rods/cones, but in the absence of these photoreceptors, light will induce Fos within melanopsin RGCs. (2) Could the reported age‐related decline in circadian photosensitivity of rodents be linked to changes in the population of melanopsin RGCs? We show that old mice experience an ～ 40% reduction in melanopsin RGCs. (3) Does the loss of inner retinal neurons affect the responses of melanopsin RGCs? Aged (～ 700 days) rd/rd cl mice lose most of their inner retina but retain the retinal ganglion cell layer. In these mice, the proportion of melanopsin RGCs that express Fos in response to light is significantly reduced. Collectively, our data suggest that melanopsin RGCs form a heterogeneous population of neurons, and that most of the light‐induced c‐fos expression within these cells is associated with the endogenous photosensitivity of these neurons.     

Prevalence of sexually transmitted diseases and human immunodeficiency virus among women attending prenatal services in Apia, Samoa

There is no routine prenatal screening for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV) in pregnancy in Samoa. Testing for chlamydial infection is not available. To gather information on pregnant women, a prevalence survey was conducted in Apia, Samoa, utilizing two prenatal hospital clinics. Pregnant (n=427) women were tested for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis using polymerase chain reaction (PCR), and for syphilis (n=441) by rapid plasmid reagin (RPR) and HIV (n=441) by enzyme-linked immunosorbent assay (ELISA). Results were: chlamydia 30.9% (132); trichomoniasis 20.8%; gonorrhoea 3.3%; syphilis 0.5%; and HIV 0%. Overall 42.7% had at least 1 STD. Young women aged <25 years were three times more likely to have a STD than older women (odds ratio=3.0, 95% confidence intervals 2.0, 4.5). The lack of inexpensive, reliable field diagnostics remain a barrier to sustainable STD control programmes for pregnant women living in developing countries.     

Oxygen modulates cell death in the proliferating retina

Many factors probably regulate the process of natural cell death during development. It is present in both the early undifferentiated retina and later following differentiation. Melanin production plays a role in regulating retinal development and when it is absent, cell proliferation and death are enhanced. Here we examine the effects of hyperoxia on this process, as oxygen has been shown to reduce cell death among differentiated photoreceptors late in development. However, in this study we examine its effects much earlier in pigmented and albino pigmentation phenotypes, when most cells are still actively dividing and are not committed to a specific fate. Newborn mice were exposed to high oxygen levels for 24 h and then returned to normal air for varying periods and their retinae examined. Hyperoxia had a dramatic effect on the number of dying cells, reducing them by almost 60% in pigmented animals and by over 80% in albinos. Following the return to normal air there was a gradual increase in their number over 360 min back to normal levels in pigmented mice; however, in albinos there was a complete rebound in levels of cell death within 40 min, reflecting the increased metabolic stress present in albino retinae due to their abnormal levels of proliferation. These results highlight the important role played by oxygen during early natural cell death in the retina and reveal the different developmental conditions present in the retinae of the two pigmentation phenotypes examined.