Pharmaceutical compounds


Certain drugs are being developed that can protect or slow the damage photoreceptors in conditions like retinitis pigmentosa and AMD. The photoreceptor cells located the back of the retina are specially designed types of nerve cells; they convert light into electrical energy and pass this signal to other nerves, and eventually to the brain where vision is perceived.

In inherited retinal degenerations the photoreceptors degenerate due to a variety of gene defects within the cell itself, leading to the build-up of waste products which slowly damages the cell and causes it to die. In conditions like AMD the photoreceptors become damaged due to the fact that the support structures surrounding the photoreceptors become damaged. Gene therapy strategies are dependent on knowing the precise gene that is affected and the advantage with these novel drug therapies is that they are independent of the causative gene for the degeneration.

These neuroprotective therapies can be broadly broken down into two main areas; anti-apoptotic agents and anti-oxidant compounds.

Anti-Apoptotic Agents

Apoptosis is the term used to describe how cells decide to switch off and die. Apoptosis is a fundamental and essential process in the body. For example, in the womb, our fingers and toes are connected to one another by a sort of webbing. Apoptosis is what causes the webbed cells to die, leaving us with 10 separate digits. However, sometimes apoptosis occurs abnormally, and in retinal degenerations it can lead to the death of the important photoreceptor cells that are required for light and vision. Many compounds are currently being investigated for their “anti-apoptotic” properties.

An example is a recent technology involving the encapsulation of human cells that are genetically modified to secrete cillary neurotrophic factor (CNTF). CNTF is a human growth factor that preferentially stimulates and protects human cells. This implant is currently in human clinical trials and initial results have been very promising, with a slowing in progression of retinitis pigmentosa in treated patients. This is a long term study and these patients will be monitored for a number of years to determine the efficacy of this treatment.

Fighting Blindness currently fund a project regarding the development of anti-apoptotic compound for retinal degeneration which can found by accessing the link below.

Fighting Blindness Funded Research Projects

2012: Bringing a neuroprotective compound closer to the clinic for the potential treatment of Retinitis Pigmentosa. For more informtation, read point 1 below.

2005: Pro-apototic BH3-only protein BIM and the regulation of photoreceptor apoptosis in retinal degredation.

1. Bringing a neuroprotective compound closer to the clinic for the treatment of retinitis pigmentosa

PI: Prof. Tom Cotter, University College Cork

The loss of photoreceptor cells via apoptosis (the process by which cells switch off and die) is a central feature of Retinitis Pigmentosa. Previous work by Professor Tom Cotter and his team in University College Cork involved screening 1000 approved drugs to look for compounds that provide an anti-apoptotic effect to retinal cells. One of those screened drugs was Norgestrel, a very safe and extensively used drug that is the active component of the contraceptive “minipill.”

“The Norgestrel seems to work by stimulating the production of a protein survival factor called FGF from neighbouring cells in the eye and this helps the light detecting cells to survive and the animals to see,” says Professor Cotter.” FGF binds to the surface of the light detecting cells and sends a signal to their DNA to up-regulate strong cells survival pathways. In other words, it ‘beefs up’ the cells, makes them stronger and better able to resist the destructive effects of the damaged gene that causes the disease.

With this project grant, Professor Cotter and his team hope to carry out longer studies in animal models of retinitis pigmentosa to see how long the protective effects last for, what is the best method to deliver the compound and which doses will be most effective. They will investigate the mechanism of action in the retina of the Norgestrel compound to see how this drug works as a photoreceptor protectant.

Fighting Blindness will invest €150,000 in this work over the next three years in order to help progress this promising treatment closer to the clinic.


There are a large number of chemicals that can act as anti-oxidants in the eye. Some can be taken orally (like vitamin supplements), and others which must be delivered directly to the eye (e.g. in the form of eye drops). There is strong basic science support for the value of lutein, zeaxanthin, and omega-3 fatty acids in promoting eye health for patients with AMD, and the scientific and medical community are eagerly awaiting the release of a large clinical trial called age-related eye disease Study 2 (AREDS2) that will be published in 2013.

New drugs and combinations of drugs are also being investigated as antioxidants. Recent work from the University of Alicante and others has demonstrated that a compound known as TUDCA is a potent antioxidant. TUDCA is found in high quantities in the bile of black bears and has been synthetically available since 1954. Mice treated with TUDCA demonstrate lower numbers of photoreceptor cell death compared to controls. TUDCA also prevents the reorganisation of the retina seen in late stage of retinal injury and maintains the network of blood vessels of the retina in a mouse model of RP. Similarly, dietary supplementation with another compound known as Safranal, which is an extract from saffron, and noted for its antioxidant properties slows photoreceptor cell degeneration, and suggests that Safranal could potentially be useful to retard retinal degeneration in patients with RP.

Another example is a recent clinical trial led by Newcastle University that has shown that the potent antioxidant, Idebenone (Catena®), improved the vision and perception of colour in patients with Leber’s hereditary optic neuropathy (LHON).

In the phase 2 clinical trial in 2011, nine patients (12 eyes) out of 36 patients (61 eyes) taking Idebenone, had vision improved to the extent that they were able to read at least one row of letters on the chart. In contrast not a single patient of the 26 who were taking the placebo improved to that extent. The Idebenone drug was shown to be safe and well tolerated. The sponsors of the trial hope to begin phase 3 of this trial in a larger group of patients in 2013. Because of the urgent unmet medical need for a treatment for LHON combined with the promising results, have led the trial sponsor Santhera Pharmaceuticals to apply for marketing approval in Europe for Cantera® and is currently under regulatory review.

Anti-Vascular Agents

The most severe (wet) form of AMD is caused by the growth of abnormal blood vessels. These blood vessels damage the photoreceptor cells mechanically by invading the same space and additionally the new blood vessels are leaky, so both blood and toxic products can leak out, damaging the photoreceptor cells.

Blood vessels are stimulated to grow by a variety of factors, one of which is a protein called vascular endothelial growth factor. This growth factor can be neutralised by injecting an antibody to it into the eye. Drugs like Lucenits® and Avastin® are antibodies, and they bind to VEGF, preventing it from stimulating the growth of new blood vessels. However, these antibodies must be injected directly into the eye on a monthly basis, which is a significant disadvantage. There are other drugs that could prevent blood vessel growth when taken orally, however they cannot get inside the eye. One of our funded projects below has investigated a strategy to get around this problem.

Fighting Blindness Funded Research Projects

2009: Age related macular degeneration: validation of novel approaches to suppression of retinal neovascularisation. For more information, read point 1 below.

1. Age-related macular degeneration: validation in mice of novel approaches to suppression of retinal neovascularisation.

Principal Researcher on this research project, Professor Pete Humphries.

Aims of this grant

In the over 50s, age-related macular degeneration (AMD) is the leading cause of sight loss in Ireland, with over 7,000 new cases in Ireland every year. AMD affects the macula – an oval shaped yellow pigmented spot in the retina. This is the part of the part of the eye responsible for central vision which allows you to see detail.

Currently many important drugs for the wet form of AMD need to be injected directly into the eye e.g. Lucentis and Avastin. This is because the cells that line the blood vessels inside the eye don’t allow drugs to pass through into the retina if they are taken orally. This research aims to develop small molecules capable of opening and closing the retina blood barrier to allow drugs taken orally and dissolved in the blood access the inside of the eye, eliminating the need for regular injections.

Links to studies mentioned in this article

(Please note: Fighting Blindness cannot be held responsible for information from other websites)

AREDS2 study: