A number of things can go wrong in any of the structures of the eye, causing Glaucoma is a group of diseases of the optic nerve that result in loss of vision or. Age-Related Eye Diseases and Conditions at a Glance. Disease or. Condition. Description. Risk Information. Symptoms/Additional Information. Age-related. Health professionals can help protect their patients from vision loss or blindness by recognizing risk factors associated with common eye diseases and.
|Language:||English, Spanish, French|
|Genre:||Academic & Education|
|Distribution:||Free* [*Registration needed]|
Welcome to Ophthalmology! In this booklet we have put together tables of core knowledge that we think you need to know and key ophthalmic disorders we think. in your practice, we have listed signs and symptoms, the equipment . Dry eye syndrome is a condition where the eyes do not make enough tears, or the tears. PDF | The doubling time of information in medicine and specifically in over the professions involved in the care of the eye and its disease.
This review provides an overview of the progress made in the area of neural stem cell research with emphasis on the eye. First, neural stem cells are defined and described. Second, their location and characterization in the mammalian eye is outlined.
Third, progress in therapeutic usage of neural stem cell is discussed. And finally, the current barriers to neural stem cell therapy are assessed in an attempt to provide a balanced view of these exciting new opportunities in treating degenerative eye diseases. This review does not include corneal stem cells; the reader is referred to an excellent review by Schwab and Isserhoff 3 on the therapeutic uses of corneal stem cells. Defining Neural Progenitors as Stem Cells The generation of cellular diversity in the brain is widely believed to be a multistep process.
The process is believed to involve multipotent progenitors whose proliferative and differentiation potentials are progressively restricted during development Fig. The progressive restriction of the developmental potential of neural progenitors, regulated by intricate cell—cell interactions, ultimately directs their differentiation into either neurons or glia. Whereas the majority of embryonic and adult neural progenitors have been demonstrated to be multipotential in terms of giving rise to three basic central nervous system CNS cell types—neurons, astrocytes, and oligodendrocytes—there is general disagreement about whether these progenitors represent a true stem cell population.
This controversy has arisen, in part, because there is no consensus on the definition of stem cells. In very general terms, stem cells can be defined as tissue-specific ancestral cells that have the potential to give rise to all differentiated cell types associated with that tissue and can self-renew—that is, they have the ability to generate a large number of identical multipotent progeny by clonal amplification.
Other properties attributed to stem cells such as asymmetrical division, mitotic quiescence, and regenerative capacity are shared by some but not all stem cells. This test requires serial transplantation of neural progenitors, which involves the recovery of transplanted progenitors and re-expansion and clonal analysis in vitro, followed by their retransplantation into another brain. At present this is an extremely difficult, if not impossible, proposal in the context of the brain.
Hence, this review takes a conservative approach and refers to these cells as neural stem cells-progenitors. Neural Stem Cells-Progenitors in the Mammalian Eye Embryos The ocular neuroepithelium is an excellent model for characterization of neural stem cells-progenitors because of its accessibility and limited cellular heterogeneity.
Furthermore, progenitors from ocular neuroepithelium are relatively well characterized in context of the factors that regulate their proliferative and differentiation potential.
Under these conditions, a subset of cells survives and, similar to striatal stem cells-progenitors, generates floating spheres of cells termed neurospheres. The neurospheres consist of proliferating cells that express the neuroectodermal stem cell marker, nestin Figs. Multilineage differentiation of EGF-responsive retinal progenitors is also supported by the presence of voltage-dependent current profiles characteristic of neurons and glia.
However, despite the demonstration of multipotentiality, these cells cannot be defined as stem cells, because attempts to serially clone them have not been successful—that is, they do not appear to self-renew. The clonal generation of retinal progenitors has been achieved only by culturing retinal progenitors obtained from embryos expressing the antiapoptotic factor bcl2, in the presence of a mixture of several growth factors.
This suggests two possibilities: The proliferating cells isolated from E17 embryos are not stem cells, but rather are neural progenitors with a limited self-renewal property, or these cells are indeed stem cells, but conditions have not been identified that promote their self-renewal in vitro. Adult The question of whether the adult derivatives of mammalian retinal neuroepithelium—harbored cells with stem cell properties was recently addressed. Two laboratories showed that the ciliary epithelium and not the neural retina in the adult mammalian eye contains neural progenitors.
These cells are multipotent and can differentiate along neuronal and glial lines. Unlike embryonic retinal progenitors, these cells can self-renew, because they clonally generate neurospheres. Therefore, they fulfill the basic criteria of stem cells.
These cells express the retinal progenitor markers Chx10, Rx, and Pax6, which suggests that they possess retina-specific properties and they can differentiate into retinal cells when exposed to conducive environment. However, because these cells are derived from pigmented ciliary epithelium, there is likelihood that they acquire stem cell properties in vitro by reprogramming or dedifferentiation.
Similar mechanisms have been invoked to explain the conversion of oligodendrocytic progenitors into neural stem cells. Therapeutic Uses of Neural Stem Cells-Progenitors Neural stem cells-progenitors can be used in two different but complementary ways to treat degenerative diseases.
Although these approaches have not yet been used in ocular diseases, studies in a number of animal models of neurodegeneration suggest that they may be helpful in treating degenerative changes in the retina. In addition, in vitro models of retinal differentiation consisting of ocular neural stem cells-progenitors, in combination with DNA microarrays, may provide a powerful means of identifying differentiation and survival-promoting genes that can serve as potential targets to treat retinal degeneration Fig.
Cell-Replacement Therapy Cell-replacement therapy exploits the plasticity of stem cells-progenitors to replace cells and repair tissues damaged by disease or injury.
There are two approaches to cell replacement therapy: replacement of damaged cells with cultured stem cells-progenitors and regeneration or replacement of damaged cells with endogenous stem cells-progenitors. The concept that neural stem cells-progenitors can be used to repopulate damaged brain areas is supported by the remarkable survival and differentiation potential of these cells when used in heterotopic transplantation. For example, hippocampal neural stem cells-progenitors transplanted in the rostral migratory zone not only survive but also migrate to the olfactory bulb where they differentiate into site-specific neurons.
For example, transplanted neural progenitors have been shown to substitute efficiently for dysfunctional oligodendrocytes by myelinating axons in animal models of myelin dysfunction.
First, the transplanted neural stem cells-progenitors must differentiate into photoreceptors. Second, the differentiated cells must establish contact with the second-order neurons.
The first positive evidence of the viability of this approach was reported by Takahashi et al. At least, two explanations are available for this failure. First, hippocampal neural stem cells may be intrinsically different from retinal stem cells and may not have the plasticity to differentiate into retina-specific neurons.
This intrinsic difference between region-specific neural stem cells is probably due to pattern formation in the developing nervous system.
A more promising approach is to use ocular stem cells-progenitors that are known to have the capacity to generate retinal neurons. Neural stem cells-progenitors isolated from either embryonic retina or the adult ciliary body possess retina-specific properties and can differentiate preferentially into cells expressing photoreceptor-specific markers when cocultured with neonatal retinal cells.
The rarity of each RED, together with the significant clinical and genetic heterogeneity that characterises this group of conditions, can make precise diagnosis and evidence-based management challenging. To improve patient care and to obtain sufficient sample sizes for research, responsible sharing of knowledge and data across centres and countries is required [ 7 ]. Adoption of comprehensive phenotype and rare disease ontologies enables this type of sharing by making data findable, accessible, interoperable, and re-usable FAIR principles [ 8 ].
Ontologies are computational tools assisting in the description, organisation and analysis of data.
An ontology provides not only a standardised set of vocabulary terms but also a classification of these entities so that terms with related meanings are connected by well-defined relationships.
Central to each ontology are terms, also known as classes, which are arranged in a hierarchical and semantically informative structure from the general high in the hierarchy to the specific low in the hierarchy [ 9 — 11 ] Fig. Ontologies consist of several distinct elements including terms nodes in the figure and relationships arrows in the figure.
Modifiers can be assigned to each term and may relate to severity mild, moderate etc. The user can specify if a specific phenotype HPO term is present or absent in an individual.
Therefore, the higher in the ontology a term is located, the more general it is and the lesser its information content defined as the negative logarithm of its probability will be This work focuses on developing the ophthalmology-related component of two widely utilized biomedical ontologies, the Human Phenotype Ontology HPO and the Orphanet Rare Disease Ontology ORDO [ 3 , 10 , 12 , 13 ].
Each term in HPO describes a distinct phenotypic feature such as a symptom e. To set a robust ontological foundation for ocular phenotypes and REDs a multi-step approach was utilized.
The HPO project commenced in with the initial aim of aiding rare disease phenotyping and diagnostics [ 9 ]. Orphanet is an international data resource that was created in to address the scarcity and fragmentation of information on rare diseases.
This unique database has grown substantially over the past 20 years by incorporating expert advice and through extensive manual curation of medical literature. In this meeting, 60 members of the European Reference Network on rare eye diseases ERN-EYE from 29 centres of 13 countries [ 14 ] worked with international experts to enrich the HPO and Orphanet classifications and to agree on a broad range of terms.