A major breakthrough has been accomplished in the use of genes to restore sight in a dog model of a retinal degeneration, called Leber’s Congenital Amourosis (LCA).
In LCA, an infant is born blind due to a retinal degeneration that affects both day and night vision. Infants with LCA typically have very little vision at birth, have nystagmus (“wondering eyes”) and have a tendency to rub their eyes excessively (oculo-digital sign). At least in some cases of LCA, the retinal degeneration is due to a mutation in gene RPE65 (the defective gene is called RPE65-/-). Once one infant is born with LCA, the same parents have a 25% chance of having another affected child. There is no known treatment for LCA and the infant with LCA faces a life with very little, if any, vision.
In the breakthrough research, collaborating researchers from a number of universities used dogs with a similar retinal degeneration as LCA and, through the marvels of gene therapy, were able to insert correct copies of RPE65 into cells that contained the defective gene RPE65-/-. The researchers injected the correct RPE65 gene (using a vector called adeno-associated virus) between the retina and another layer of cells critical for vision called the RPE (Retinal Pigment Epithelium). The retina is that part of the eye that contains the cone and rod photo-receptors needed for day vision and night vision, respectively. The RPE cells provide nourishment, including vitamin A, to the photo-receptors.
Ten months after the initial gene therapy, the treated dogs were found to have electroretinogram (ERG) or retinal electrical responses that appeared normal. The treated dogs also had pupil responses to light and had molecular findings indicating that the injected, corrected RPE65 cells were present. Most importantly, after gene therapy the treated dogs were able to use the treated eyes for sight! For example, the treated eyes could be used to follow one of the researchers walk across the room while the untreated eyes of the same dogs did not elicit a following response.
In contrast, when the same corrected gene RPE65 was injected into the gel part of the eye, called the vitreous, the gene therapy had, as expected, no change in vision, ERG or other measures. This latter condition is called a “control condition”, commonly used in research.
The significance of this gene therapy breakthrough cannot be overstated. While it will take several years of additional testing and experimentation in such animal models to ensure safety for human experimentation and treatment, the horizon looks promising. Such gene therapy could eventually be used to treat patients with LCA and possibly other genetic eye diseases such as Retinitis Pigmentosa (RP), the latter affects 1 in every 3600 people.
The Ohio LIONS Eye Research Foundation funds gene research in a number of eye diseases, including diseases of the cornea, retina and optic nerve. Gene research is being undertaken and funded at numerous sites including Case Western Reserve University, University of Cincinnati and Medical College of Ohio in Toledo. Many predict that within 10 years or so that there will be gene therapies for a host of eye diseases that cause blindness. With your help, the Ohio LIONS Eye Research Foundation will continue to provide seed money for such research…your vision and ours’ may depend upon it.
Acland et al. Gene Therapy restores vision in a canine model of childhood blindness. Nature Genetics, vol 28, p92 – 95, May, 2001.