October 2014

Some exciting results from trails looking at embryonic stem cells in treating blindness! The future in this fascinating area looks bright. A basic science paper explains a new mechanism involved in photoreceptor cell death. And lastly may reading glasses be a thing of the past? Corneal inlays show some promising results.

 

Enjoy!

 

Ellie

 

How safe are human embryonic stem cell transplants?

 

Evidence of the medium- to long-term safety of transplanting human embryonic stem cells has been published for the first time, in a report in The Lancet.

 

Since 1981, when pluripotential cell cultures were first derived, human embryonic stem cells (hESCs) have been considered to be a potential source of cells to treat diseases caused by tissue loss or dysfunction. However, scientists were concerned that the self-renewing abilities of these cells could lead to problems such as tumor development. Despite plenty of animal studies over the past 3 decades, there have been no assessments of the long-term safety or effectiveness of hESCs in humans.

Embryonic stem cells have the potential to become any cell type in the body, but transplantation has been complicated by problems including the risk of teratoma formation and immune rejection. As a result, immunoprivileged sites (that do not produce a strong immune response) such as the eye have become the first parts of the human body to benefit from this technology.

Across two studies, hESCs were transplanted into 18 patients with severe vision loss. Nine of the patients had atrophic age-related macular degeneration and nine had Stargardt macular dystrophy - these conditions eventually cause complete blindness and there are no effective treatments for them. The participants were injected with a dose of either 50,000, 100,000, or 150,000 retinal cells under the retina in their eye that had the worst vision. The authors found that the hESC-derived cells were well tolerated for up to 37 months after transplantation. During a median follow-up of 22 months, no safety concerns were found. Some adverse events were associated with surgery and immunosuppression, but the authors state that these events were not related to the hESC-derived cells.

Follow-up testing in the first year after transplant demonstrated that eight of the patients were now able to read over 15 additional letters. In seven patients, visual acuity remained the same or improved. One patient, however, reported a decrease in visual acuity by more than 10 letters.

 

References:

Steven D Schwartz, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies,., The Lancet, http://dx.doi.org/10.1016/ S0140-6736(14)61820-1, published online 15 October 2014.

McNamee, D. (2014, October 15). "How safe are human embryonic stem cell transplants?." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/articles/283913.php. Accessed October 20th 2014.

Discovery of a new mechanism that can lead to blindness

It has been discovered that a protein found in the retina plays an essential role in the function and survival of light-sensing cells that are required for vision. These findings could have a significant impact on our understanding of retinal degenerative diseases that cause blindness.

A process called compartmentalization was studied, which establishes and maintains different compartments within a cell, each containing a specific set of proteins. This process is crucial for neurons (nerve cells) to function properly. Compartments within a cell are much like different parts of a car, in the same way that gas must be in the fuel tank in order to power the car's engine, proteins need to be in a specific compartment to properly exercise their functions. A good example of compartmentalization is observed in a specialized type of light-sensing neurons found in the retina, the photoreceptors, which are made up of different compartments containing specific proteins essential for vision.

The authors identified a new mechanism that explains how compartmentalization is achieved within photoreceptor cells. More specifically, a protein called Numb was found to function like a traffic controller to direct proteins to the appropriate compartments. In the absence of Numb, photoreceptors are unable to send a molecule essential for vision to the correct compartment, which causes the cells to progressively degenerate and ultimately die.

This is important because the death of photoreceptor cells is known to cause retinal degenerative diseases in humans that lead to blindness. This work therefore provides a new piece of the puzzle to help us better understand how and why the cells die. This could eventually have a substantial impact on the development of treatments for retinal degenerative diseases, like retinitis pigmentosa and Leber's congenital amaurosis, by providing novel drug targets to prevent photoreceptor degeneration.

References:

Ramamurthy et al. Numb Regulates the Polarized Delivery of Cyclic Nucleotide-Gated Ion Channels in Rod Photoreceptor Cilia The Journal of Neuroscience. 2014, 34(42): 13976-13987

IRCM. (2014, October 17). "Discovery of a new mechanism that can lead to blindness." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/284021.php.
 Accessed 20th October

 

Corneal inlays may remove need for reading glasses

Implantable eye devices called corneal inlays are designed to correct presbyopia - the age-related loss of near vision that affects over a billion people worldwide. Delegates at a recent scientific meeting learned how one such device - the KAMRA inlay - improved near vision well enough for 80% of study participants to be able to read a newspaper without impairing far distance vision for common activities such as driving.

Currently, there are three designs of corneal inlays, each varying in size, material and mechanism of action.

Generally, corneal inlays have complications such as haziness that can be treated with steroids, but newer designs are managing to minimize these. If necessary, corneal inlays can be removed, making the treatment reversible, unlike other procedures such as LASIK laser eye surgery for presbyopia.

John Vukich, a clinical adjunct professor in ophthalmology and vision sciences at the University of Wisconsin, Madison, presented the results of a study on the efficacy of the KAMRA corneal inlay at AAO 2014, the 118th annual meeting of the American Academy of Ophthalmology, that is running from October 17th to 21st in Chicago, IL.

Prof. Vukich says corneal inlays are "a great opportunity to improve vision with a safety net of removability," and the study results show the KAMRA inlay is "a solution that truly delivers near vision that transitions smoothly to far distance vision."

The KAMRA inlay is a thin, flexible ring with a diameter of 3.8 mm and a hole measuring 1.6 mm in the middle. Once implanted in the cornea - the clear tissue covering the front of the eye - it acts like a camera aperture, adjusting the depth of field to enable near and far vision. It takes about 10 minutes to implant the inlay, and the patient only needs a local anesthetic to numb the surface of the eye.

A prospective non-randomized study of the KAMRA inlay was carried out in 507 non-nearsighted patients with presbyopia aged between 45 and 60 who attended clinics in different parts of the US, Europe and Asia. After implanting the devices, they followed the patients for 3 years. Authors found that in 83% of the presbyopic patients, the corneal implant allowed them to see with 20/40 vision or better over the follow-up period. This is considered the standard for being able to read newsprint or drive a vehicle without requiring glasses. On average, the participants gained 2.9 lines on a reading chart, and the results remained steady over the follow-up.

The KAMRA inlay is already available for commercial use in Asia, Europe and South America. I

Two other types of corneal inlays - the Raindrop Near Vision Inlay that works by changing the shape of the cornea and the Presbia Flexivue Microlens that changes the refractive index of the cornea - are also in development for the US market.

References:

Treating emmetropic presbyopes with a small aperture inlay: three year results, presented by John Vukich, at AAO 2014, 118th annual meeting of the American Academy of Ophthalmology, October 17 -21, Chicago.

Paddock, C. (2014, October 20). "Corneal inlays may remove need for reading glasses." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/articles/284095.php. Accessed 27th October 2014.