One day, blind people may have their sight restored thanks to a new method of molecular therapy. It makes use of genes acquired from an unlikely source, algae. Recently a group of American scientists proved, that the therapy is successful in murine model. During a described trial (1), solution containing viruses, which carry the algal genes, was injected into the eyes of blind mice. It turned out that retinal cells became sensitive to light and mice could easily find their way out of a maze. According to WHO (2), it has been estimated that about 39 million people worldwide suffer from a severe vision impairment. Perhaps we could put an end to this problem by using a power of nature mixed with technological advance.
Top three causes of blindness in developed countries are glaucoma, agerelated macular degeneration (AMD) and diabetic retinopathy. The two last disorders share the same endpoint, which is a degeneration of neural cells of the eye. Although recent treatment advances can slow down the course of a disease, many patients still suffer from irreversible loss of vision. Retinitis pigmentosa (RP) is also mentioned as a hereditary condition that cannot be cured and inevitably progresses to blindness. The use of stem cells (3) and electronic implants (4) are examples of intensive attempts to find a cure for vision impairment, whereas gene therapy seems to be one of the most promising.
As a result of retinopathy, photoreceptor cells are destroyed. Thus the light signal cannot be received by ganglion cells of the retina and then transmitted to central nervous system. The main idea of presented gene therapy is to make the bipolar cells of retina, which form the second layer of retina, function as photoreceptors by producing a special light-sensitive protein. Channelrhodopsin-2 (ChR2) naturally appears in unicellular algae and takes part in phototaxis. Here, it receives the light signal and transfers it to ganglion cells. The gene encoding ChR2 is delivered to retina by a “tame” virus, which capsid was specially modified so as to enhance the transmission.
The team of researchers tested their method using three groups of mice: two groups of strains naturally blind in a similar way to people with RP and AMD and one with normal vision. One group of blind animals was treated with the gene therapy, while the other two groups were not. They injected the substance containing viruses subretinally and after 10 weekes the expression of ChR2 protein was assessed by means of immunolabeling. Physiological efficacy of the therapy was measured by taking into consideration a required intensity of light to generate an impulse. Behavioral tests involved placing mice in a water maze, where the exit was guided by light. Scientists checked a biodistribution, ocular toxicity and systemic immunity of the probes.
The results were successful. The expression of light-sensitive protein was high in bipolar cells and it was maintained till the 10th month, which was an endpoint of the study. It means that the therapy has a potential to be a onetime treatment. What is more, expression of ChR2 in bipolar cells can drive light-evoked responses in diseased retinas at a light intensity normally encountered during daylight activity. In the behavioural study, treated mice performed significantly better than their untreated counterparts. Biodistribution was basically limited to an eye, with little presence in other tissues. According to laboratory tests, no immune or toxic reaction to the body was registered.
Nowadays the world of medicine is being constantly under pressure of the society, which waits for major breakthroughs to cure common conditions. Scientists make a big effort to meet their wishes and investigate surprising solutions to diseases. Extracting a gene from algae and putting it into a virus led to restoring sight of mice. With help of the most up-to-date weapons of medicine, perhaps we can fight the diseases that seem untreatable. Viral delivery of protein ChR2 seems to be a safe, efficient and robust treatment option, which will hopefully one day become available for a large group of patients.
Written by: Natalia Neumann
1.Mol Ther. 2011 Apr 19. Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness. Doroudchi MM, Greenberg KP, Liu J, Silka KA, Boyden ES, Lockridge JA, Arman AC, Janani R, Boye SE, Boye SL, Gordon GM, Matteo BC, Sampath AP, Hauswirth WW, Horsager A.
3.Can J Ophthalmol. 2010 Aug;45(4):333-41. Current approaches and future prospects for stem cell rescue and regeneration of the retina and optic nerve. Dahlmann-Noor A, Vijay S, Jayaram H, Limb A, Khaw PT.
4.Proc Biol Sci. 2011 May 22;278(1711):1489-97. Epub 2010 Nov 3. Subretinal electronic chips allow blind patients to read letters and combine them to words. Zrenner, E, Bartz-Schmidt, KU, Benav, H, Besch, D, Bruckmann, A, Gabel, VP et al.