Tag Archives: cornea

Eye macro photography.

Scientists are now able to bio-print corneas

This research could usher in corneas-on-demand, offering hope for the millions of patients awaiting transplant.

Eye macro photography.

Image via Publicdomainpictures.

Researchers at the Newcastle University, UK, have successfully 3D-printed human corneas — a world first. Their technique could eventually lead to a cornea mass-production system that could help the millions of people waiting for a transplant.

A feast for the eye

The cornea is the outer layer of the human eye and plays a central role in focusing our vision. It’s also a part of the eye that doesn’t always age gracefully and is susceptible to damage from infections or disease. As such, there are over 10 million people worldwide who risk corneal blindness from diseases such as trachoma (an infectious eye disease), and almost 5 million who are completely blind due to burns, lacerations or abrasion of the cornea.

Most of them are awaiting a transplant, but there are very few donors.

The team’s work aims to address this shortage. They used a mix of human corneal stromal (stem) cells harvested from donated healthy corneas, alginate, and collagen to create a firm but printable bio-ink. This material is based on previous work, in which the team developed a similar hydrogel that could keep cells alive for weeks at a time.

They fed this substance through a simple, low-cost 3D bio-printer into concentric circles roughly the shape of a human cornea. According to their scientific paper, it took under 10 minutes to print their proof-of-concept cornea. The final step is allowing this structure to grow into a cornea on a culture dish.

“Many teams across the world have been chasing the ideal bio-ink to make this process feasible,” says lead researcher Che Connon, a Professor of Tissue Engineering at Newcastle University.

“[The gel] keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer.”

The team also showed they can build corneas to match a patient’s unique needs and specifications. The dimensions required for this were originally taken from an actual cornea, the team writes. In the future, a simple scan of a patient’s eye will enable doctors to print a cornea that perfectly matches the size and shape of their eyeballs.

The 3D-printed corneas will have to undergo a lot of testing, probably over the span of a few years, before they’ll even be considered for use in transplants, the team explains. However, the ability to produce enough of them to treat all those awaiting transplant as well as the precision with which they can be crafted will is a game-changing prospect — one that’s bound to spur on further development.

The paper “3D bioprinting of a corneal stroma equivalent” has been published in the journal Experimental Eye Research.

How the eye works

 

Image via flickr. 

Doing some light reading

Touch interprets changes of pressure, texture and heat in the objects we come in contact with. Hearing picks up on pressure waves, and taste and smell read chemical markers. Sight is the only sense that allows us to make heads and tails of some of the electromagnetic waves that zip all around us — in other words, seeing requires light.

Apart from fire (and other incandescent materials), bioluminiscent sources and man-made objects (such as the screen you’re reading this on) our environment generally doesn’t emit light for our eyes to pick up on. Instead, objects become visible when part of the light from other sources reflects off of them.

Let’s take an apple tree as an example. Light travels in a (relatively) straight line from the sun to the tree, where different wavelengths are absorbed by the leaves, bark and apples themselves. What isn’t absorbed bounces back and is met with the first layer of our eyes, the thin surface of liquid tears that protects and lubricates the organ. Under it lies the cornea, a thin sheet of innervated transparent cells.

Behind them, there’s a body of liquid named the aqueous humor. This clear fluid keeps a constant pressure applied to the cornea so it doesn’t wrinkle and maintains its shape. This is a pretty important role, as that layer provides two-thirds of the eye’s optical power.

Anatomy of the eye.
Image via flikr

The light is then directed through the pupil. No, there’s no schoolkids in your eye; the pupil is the central, circular opening of the iris, the pretty-colored part of our eyes. The iris contracts or relaxes to allow an optimal amount of light to enter deeper into our eyes. Without it working to regulate exposure our eyes would be burned when it got bright and would struggle to see anything when it got dark.

The final part of our eye’s focusing mechanism is called the crystalline lens. It only has half the focusing power of the cornea but its most important function is that it can change how it does this. The crystalline is attached to a ring of fibrous tissue on its equator, that pull on the lens to change its shape (a process known as accommodation), allowing the eye to focus on objects at various distances.

Fun fact: You can actually observe how the lens changes shape. Looking at your monitor, hold your up hands some 5-10 centimeters (2-4 inches) in front of your eyes and look at them till the count of ten. Then put them down; those blurry images during the first few moments and the weird feeling you get in your eyes are the crystalline stretching to adapt to the different focal vision.
Science at its finest.

After going through the lens, light passes through a second (but more jello-like) body of fluid and falls on an area known as the retina. The retina lines the back of the eye and is the area that actually processes the light. There are a lot of different parts of the retina working together to keep our sight crispy clear, but three of them are important in understanding how we see.

  • First, the macula. This is the “bull’s eye” of the retina. At the center of the macula there’s a slight dip named the fovea centralis (fovea is latin for pit). As it lies at the focal point of the eye, the fovea is jam-packed with light sensitive nerve endings called photoreceptors.
  • Photoreceptors. These differentiate in two categories: rods and cones. They’re structurally and functionally different, but both serve to encode light as electro-chemical signals.
  • Retinal pigment epithelium. The REP is a layer of dark tissue whose cells absorb excess light to improve the accuracy of our photoreceptors’ readings. It also delivers nutrients to and clears waste from the retina’s cells.

So far you’ve learned about the internal structure of your eyes, how they capture electromagnetic light, focus it and translate it into electro-chemical signals. They’re wonderfully complex systems, and you have two of them. Enjoy!

There’s still something I have to tell you about seeing, however. Don’t be alarmed but….

The images are all in your head

While eyes focus and encode light into the electrical signals our nervous system uses to communicate, they don’t see per se. Information is carried by the optical nerves to the back of the brain for processing and interpretation. This all takes place in an area of our brain known as the visual cortex.

Brain shown from the side, facing left. Above: view from outside, below: cut through the middle. Orange = Brodmann area 17 (primary visual cortex)
Image via wikipedia

Because they’re wedged in your skull a short distance apart from each other, each of your eyes feeds a slightly different picture to your brain. These little discrepancies are deliberate; by comparing the two, the brain can tell how far an object is. This is the mechanism that ‘magic eye’ or autostereogram pictures attempt to trick, causing 2D images to appear three dimensional.  Other clues like shadows, textures and prior knowledge also help us to judge depth and distance.

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The neurons work together to reconstruct the image based on the raw information the eyes feed them. Many of these cells respond specifically to edges orientated in a certain direction. From here, the brain builds up the shape of an object. Information about color and shading are also used as further clues to compare what we’re seeing with the data stored in our memory to understand what we’re looking at. Objects are recognized mostly by their edges, and faces by their surface features.

Brain damage can lead to conditions that impair object recognition (an inability to recognize the objects one is seeing) such as agnosia.  A man suffering from agnosia was asked to look at a rose and described it as ‘about six inches in length, a convoluted red form with a linear green attachment’. He described a glove as ‘a continuous surface infolded on itself, it appears to have five outpouchings’. His brain had lost its ability to either name the objects he was seeing or recognize what they were used for, even though he knew what a rose or a glove was. Occasionally, agnosia is limited to failure to recognize faces or an inability to comprehend spoken words despite intact hearing, speech production and reading ability.

The brain also handles recognition of movement in images. Akinetopsia, a movement-recognition impairing condition is caused by lesions in the posterior side of the visual cortex. People suffering from it stop seeing objects as moving, even though their sight is otherwise normal. One woman, who suffered such damage following a stroke, described that when she poured a cup of tea the liquid appeared frozen in mid-air, like ice. When walking down the street, she saw cars and trams change position, but not actually move.

restored_cornea

Better, simple way to regrow damaged corneas shines hope for blind patients

restored_cornea

A restored, functioning cornea found in a mouse, that used human harvested limbal stem cells. Image:  Kira Lathrop, Bruce Ksander, Markus Frank, and Natasha Frank

A novel and highly effective technique was found to enhance regrowth of human corneal tissue to restore vision, using a newly identified molecule that acts as a marker for limbal cells – stem cells that are paramount to retinal regeneration. The findings could greatly improve the vision of patients suffering from severe burns, victims of chemical injury, and others with damaging eye diseases.

Eyeing elusive stem cells

A healthy, transparent ocular surface is made up of non-keratinized, stratified squamous epithelium that is highly differentiated. The corneal epithelium is constantly renewed and maintained by the corneal epithelial stem cells, or limbal stem cells (LSCs) that are presumed to reside at the limbus, the junction between the cornea and conjunctiva. Patients who have lost these special stem cells due to disease or injury typically go blind. In fact, there are over 3.2 million people worldwide recognized as bilateral blind from corneal diseases, most of which were struck by limbal stem cell deficiency (LSCD).

Typically, doctors use tissue or cell transplants to help the cornea regenerate, but since they never know whether there are any actual limbal stem cells in the grafts, or how many, the results have always been inconsistent. A new collaborative effort that joins scientists from the Massachusetts Eye and Ear/Schepens Eye Research Institute, Boston Children’s Hospital , Brigham and Women’s Hospital, and the VA Boston Healthcare System may change this.

 In this study, researchers were able to use antibodies detecting the marker molecule to zero in on the stem cells in tissue from deceased human donors and use it to regrow anatomically correct, fully functional human corneas in mice.

In this study, researchers were able to use antibodies detecting the marker molecule to zero in on the stem cells in tissue from deceased human donors and use it to regrow anatomically correct, fully functional human corneas in mice.

The researchers found that an antibody, known as ABCB5, was being produced in tissue precursor cells in human skin and intestine. Tests on a mouse model showed ABCB5 also occurs in limbal stem cells and is required for their maintenance and survival, and for corneal development and repair. Essentially, ABCB5 can be used as an effective marker to zero in on the limbal stem cells. For instance, mice lacking a functional ABCB5 gene lost their limbal stem cells, and their corneas healed poorly after injury.

“Limbal stem cells are very rare, and successful transplants are dependent on these rare cells,” said Bruce Ksander of Mass. Eye and Ear, co-lead author on the study with postdoctoral fellow Paraskevi Kolovou. “This finding will now make it much easier to restore the corneal surface. It’s a very good example of basic research moving quickly to a translational application.”

Using ABCB5 antibodies, the researchers successfully identified the LSCs in tissue from deceased human donors, then used these to regrow anatomically correct, fully functional human corneas in mice.

“ABCB5 allows limbal stem cells to survive, protecting them from apoptosis [programmed cell death],” said Markus Frank. “The mouse model allowed us for the first time to understand the role of ABCB5 in normal development, and should be very important to the stem cell field in general,” according to Natasha Frank.

Rewriting the anatomy books – new layer of human cornea discovered

Scientists at The University of Nottingham have come across what can be a monumental discovery, demonstrating for the first time a new layer of the human cornea. The layer, which was described in a paper in Ophthalmology, could help surgeons to dramatically improve outcomes for patients with severe cornea affections and those undergoing surgery.

cornea

The new layer has been named Dua’s layer, after academic Professor Harminder Dua, who made the discovery.

“This is a major discovery that will mean that ophthalmology textbooks will literally need to be re-written. Having identified this new and distinct layer deep in the tissue of the cornea, we can now exploit its presence to make operations much safer and simpler for patients,” says Dua, a professor of ophthalmology and visual sciences. “From a clinical perspective, there are many diseases that affect the back of the cornea which clinicians across the world are already beginning to relate to the presence, absence or tear in this layer.”

The cornea is the transparent part of the front of the eye which covers the iris, pupil, and anterior chamber. Along with the anterior chamber, the cornea acts like a lens, refracting and bending light to best suit the view. It is responsible for about two-thirds of the eye’s total optical power.

The newly discovered layer is just 15 microns thick – which may not seem like much, but when you compare it to the cornea’s entire thickness, which is about 550 microns, it becomes significant. Ophtalmologists proved the existence of this layer by simulating human corneal transplants and grafts on eyes donated for research purposes to eye banks located in Bristol and Manchester.

Their discovery has the potential to help hundreds of thousands of people, or even more – giving a better understanding on corneal problems and providing better solution, both in terms of treatment and surgery.

Full paper here

Artificial Cornea Saves Eyesight

 

cornea

With the growing number of people with eye problems it is harder and harder to find answers to problems raised;  some cases are so bad that there is no other sollution and a cornea transplant is needed. Every year, in Germany alone, around 7000 people wait for a new cornea to save their eyesight. The bad thing is that there are not nearly that many around.

In an EU project, researchers have developed an artificial cornea which is to be clinically tested in early 2008. A man who has a damaged or worse cornea because of a congenital malformation, hereditary disease or corrosion is at risk of going blind, and often the only solution is to implant a donor cornea. Many attempts have therefore been made at producing artificial corneas, so far with little success. This is due to the conflicting requirements imposed; it has to grow firmly but the cells have to deposit themselves at the center of the cornea, as this impairs the patient’s vision.

The research scientists at the Fraunhofer Institute for Applied Polymer Research (IAP) in Potsdam and the Department of Ophthalmology at the University Hospital of Regensburg have worked with other colleagues in the EU-funded CORNEA project and they have found a solution.

“Our artificial corneas are based on a commercially available polymer which absorbs no water and allows no cells to grow on it,” says IAP project manager Dr. Joachim Storsberg. “Once our partner Dr. Schmidt Intraokularlinsen GmbH has suitably shaped the polymers, we selectively coat the implants: We lay masks on them and apply a special protein to the edge of the cornea, which the cells of the natural cornea can latch onto. In this way, the cornea implant can firmly connect with the natural part of the cornea, while the center remains free of cells and therefore clear.”

They have tested the corneas in the laboratory and found that their cells graft very well at the edge. This means that the optical center of the implant manages to stay clear. The first implants have already been tested in rabbits’ eyes and the results are very good so humans are probably going to benefit from this.