Lecture 7 (Embryonic & Adult Stem Cells) Flashcards
Briefly summarise the early history of stem cell transplantation.
Work on adult stem cell transplantation started on bone marrow stem cells in the 1950s and the first successful bone marrow transplant was carried out at the University of Minnesota in 1968.
What is the function of the cornea?
The cornea acts as a powerful lens, and is responsible for around two thirds of the light refraction onto the retina, which is then able to convert the light energy into nerve impulses.
Describe the tear film and it’s associated disorders.
The tear film provides an interface between air and the ocular surface. It also lubricates the eyelids, provides and smooth optical surface, and acts as an anti-bacterial system due to it’s constituent lysozymes and immunoglobulins.
There are many clinical disorders due to an abnormal tear film, the most common of which is keratoconjunctivitis sicca, or dry eye. This is due to the insufficient production of tear fluid, which is ordinarily caused by the degeneration of the lacrimal glands, with typical onset occuring during late middle age. The consequences of dry eye syndrome range from subtle but constant irritation, to ocular inflammation of the anterior tissues of the eye and the destruction of the epithelial stem cells.
Describe the structure and function of the anterior corneal epithelium.
The anterior corneal epithelium protects the tissue from mechanical damage, which is typically caused by exposure to UV radiation or infectious agents, with the epithelial tight junctions preventing these agents, and the tear film, from entering the stroma. The corneal epithelium is about 5 layers thick and has a basement membrane called Bowman’s layer. The corneal epithelium is maintained by the corneal epithelial stem cells which are located on the limbus (the outer edge of the cornea) and, if damaged, can repair itself within days.
Describe the structure and function of the corneal stroma and it’s associated disorders.
The corneal stroma makes up over 90% of the thickness of the cornea, and consists of regular diameter collagen fibrils (mostly type I) embedded in a matrix of proteoglycans. The stroma is made up of layers called lamellae, with each lamellae comprised of collagen fibrils running at right angles to the fibrils of adjacent lamellae. This arraignment is very like plywood and gives the cornea great strength. There is also a sparse population of cells called keratocytes.
The collagen fibrils in the corneal stroma are packed regularly. This means that when light is scattered by the fibrils, only light which is scattered parallel to the incident light combines constructively, with light scattered at all other angles combining destructively. This means that if the collagen fibrils are disrupted from their regular arrangement, then the cornea becomes opaque. The stroma is especially vulnerable. There are many corneal diseases which result in disruption to the delicate arrangement of the collagen fibres in the corneal stroma leading to corneal opacity. The most prominent of these diseases is a condition called macular corneal dystrophy, a genetic disease which results in the production of an abnormal form of a proteoglycan called keratan sulphate.
Describe the structure and function of the corneal endothelium and it’s associated disorders.
On the inner surface of the cornea is single layer of cells called the cornea endothelium. The prime function of this cell layer is to pump water from the stroma to the aqueous humor. Water constantly leaks from the aqueous into the corneal stroma; if this is was not pumped back into the aqueous by the endothelium, the cornea would swell and become opaque. Endothelial cells cannot proliferate, and if they are lost or damaged this leads to corneal oedema. Oxygen gets to the endothelial cells by diffusion from the outer surface of the cornea.
Fuchs’ dystrophy is the most common reason for corneal transplants, with onset usually between 40 and 50 years of age. Fuch’s dystrophy is characterised by an inability to maintain proper hydration of cornea due to endothelium, and results in stromal swelling, epithelial edema, and subepithelial scarring.
Describe the causes and symptoms of limbal stem cell deficiency.
A deficiency of limbal stem cells occurs in a variety of disorders.
Some, such as aniridia are genetic, and occur as the result of a genetic (pax6) mutation where the limbal stem cells do not develop properly.
More commonly, however, limbal stem cell deficiency results from acquired factors such as:
chemical or thermal injury
Severe dry eye
ultraviolet and ionizing radiation
Stevens Johnson syndrome (immune disease)
advanced ocular pemphigoid (immune disease)
contact lens abuse
multiple surgeries
extensive microbial infection.
Limbal stem cell deficiency is characterised by:
Conjunctival invasion Vascularisation Inflammation Fibrous tissue ingrowths Stromal swelling and scarring
