Located between vessels of the choriocapillaris and light-sensitive outer segments of the photoreceptors, the retinal pigment epithelium (RPE) closely interacts with photoreceptors in the maintenance of visual function. Increasing knowledge of the multiple functions performed by the RPE improved the understanding of many diseases leading to blindness. This review summarizes the current knowledge of RPE functions and describes how failure of these functions causes loss of visual function. Mutations in genes that are expressed in the RPE can lead to photoreceptor degeneration. On the other hand, mutations in genes expressed in photoreceptors can lead to degenerations of the RPE. Thus both tissues can be regarded as a functional unit where both interacting partners depend on each other.

The Retinal Pigment Epithelium in Visual Function

We have identified a cell type in 7-day-old rat optic nerve that differentiates into a fibrous astrocyte if cultured in the presence of fetal calf serum and into an oligodendrocyte if cultured in the absence of serum. In certain culture conditions some of these cells acquire a mixed phenotype, displaying properties of both astrocytes and oligodendrocytes. These observations suggest that fibrous astrocytes and oligodendrocytes develop from a common progenitor cell and provide a striking example of developmental plasticity and environmental influence in the differentiation of CNS glial cells.

A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium

Degeneration and regeneration of the nervous system

Mice Lacking p27Kip1 Display Increased Body Size, Multiple Organ Hyperplasia, Retinal Dysplasia, and Pituitary Tumors

Literature data on compounds both well- and poorly-absorbed in humans were used to build a statistical pattern recognition model of passive intestinal absorption. Robust outlier detection was utilized to analyze the well-absorbed compounds, some of which were intermingled with the poorly-absorbed compounds in the model space. Outliers were identified as being actively transported. The descriptors chosen for inclusion in the model were PSA and AlogP98, based on consideration of the physical processes involved in membrane permeability and the interrelationships and redundancies between available descriptors. These descriptors are quite straightforward for a medicinal chemist to interpret, enhancing the utility of the model. Molecular weight, while often used in passive absorption models, was shown to be superfluous, as it is already a component of both PSA and AlogP98. Extensive validation of the model on hundreds of known orally delivered drugs, “drug-like” molecules, and Pharmacopeia, Inc. compounds, whic...

Prediction of drug absorption using multivariate statistics.

Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation.

Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis pro- motes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione (DPD)) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrha- lis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. ca- tarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via inter- species quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. More- over, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm. IMPORTANCE Otitis media (OM) is one of the most common childhood infections and is a leading reason for antibiotic prescrip- tions to children. Chronic and recurrent OM involves persistence of bacteria within biofilm communities, a state in which they are highly resistant to immune clearance and antibiotic treatment. While it is clear that most of these infections involve multiple species, the vast majority of knowledge about OM infections has been derived from work involving single bacterial species. There is a pressing need for better understanding of the impact of polymicrobial infection on the course, severity, and treatabil- ity of OM disease. In this study, we show that communication between bacterial species promotes bacterial persistence and resis- tance to antibiotics, which are important considerations in the diagnosis, prevention, and treatment of OM. Moreover, the re- sults of this study indicate that successful preventive measures against H. influenzae could reduce the levels of disease caused by M. catarrhalis.

https://mbio.asm.org/content/mbio/1/3/e00102-10.full.pdf

James E. Turner

Papers

Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation.

Indirect Pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in Polymicrobial Otitis Media Occurs via Interspecies Quorum Signaling

Retinal pigment epithelial cell transplantation in RCS rats: Normal metabolism in rescued photoreceptors

Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and long-term survival characteristics.

Optimal conditions for long-term photoreceptor cell rescue in RCS rats: the necessity for healthy RPE transplants.