Genetics of ocular disease Part 1: Basic concepts: cells, chromosomes and inheritance

This series of articles describes the basic elements of genetics necessary to understand the new advances and the impact these advances will have on the study and treatment of ocular disease. The first article describes the patterns of inheritance of human characteristics, how they are transmitted between the generations and the structure of chromosomes.

Acanthamoeba polyphaga trophozoite binding of representative fungal single cell forms

Acanthamoeba polyphaga trophozoites bind yeast cells of Candida albicans isolates within a few hours, leaving few cells in suspension or still attached to trophozoite surfaces. The nature of yeast cell recognition, mediated by an acanthamoebal trophozoite mannose binding protein is confirmed by experiments utilizing concentration dependent mannose hapten blocking. Similarly, acapsulate cells of Cryptococcus neoformans are also bound within a relatively short timescale. However, even after protracted incubation many capsulate cells of Cryptococcus remain in suspension, suggesting that the capsulate cell form of this species is not predated by acanthamoebal trophozoites. Further aspects of the association of Acanthamoeba and fungi are apparent when studying their interaction with conidia of the biocontrol agent Coniothyrium minitans. Conidia which readily bind with increasing maturity of up to 42 days, were little endocytosed and even released. Cell and conidial surface mannose as determined by FITC-lectin binding, flow cytometry with associated ligand binding analysis and hapten blocking studies demonstrates the following phenomena. Candida isolates and acapsulate Cryptococcus expose most mannose, while capsulate Cryptococcus cells exhibit least exposure commensurate with yeast cellular binding or lack of trophozoites. Conidia of Coniothyrium, albeit in a localized fashion, also manifest surface mannose exposure but as shown by Bmax values, in decreasing amounts with increasing maturity. Contrastingly such conidia experience greater trophozoite binding with maturation, thereby questioning the primacy of a trophozoite mannose-binding-protein recognition model.

Discriminating antigen and non-antigen using proteome dissimilarity II:viral and fungal antigens

Immunogenicity arises via many synergistic mechanisms, yet the overall dissimilarity of pathogenic proteins versus the host proteome has been proposed as a key arbiter. We have previously explored this concept in relation to Bacterial antigens; here we extend our analysis to antigens of viral and fungal origin. Sets of known viral and fungal antigenic and non-antigenic protein sequences were compared to human and mouse proteomes. Both antigenic and non-antigenic sequences lacked human or mouse homologues. Observed distributions were compared using the non-parametric Mann-Whitney test. The statistical null hypothesis was accepted, indicating that antigen and non-antigens did not differ significantly. Likewise, we could not determine a threshold able meaningfully to separate non-antigen from antigen. We conclude that viral and fungal antigens cannot be predicted from pathogen genomes based solely on their dissimilarity to mammalian genomes.

Fungal infection of the eye (ocular mycosis)

Although not as important as bacteria or viruses as a cause of eye infection, a large number of fungal species have now been recorded in association with the eye. In addition, several species have been implicated as a cause of eye infection (‘ocular mycosis’) and some may even cause life-threatening conditions. Ocular mycoses are being reported more frequently as a consequence of new medical practice and the increased numbers of immuno-compromised patients in the population, e.g., patients receiving radiation treatment or chemotherapy. This article describes the most common conditions caused by fungi which can affect the different structures of the eye, the importance of fungal contamination of materials as a source of eye infection, and the methods available for treatment.

Studies in fungal biology

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A bio-adhesive formulation for the delivery of anti-fungal agents to the oesophagus

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