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Congenital Blindness and Eye Diseases

Genetic diseases of the eye can arise from one of 160 mutations. Because the eye does not normally mount an immune response, the eye may not reject the new genetic material or the new cells as readily as other tissues. Gene therapy trials for 2 eye diseases, Leber congenital amaurosis (LCA) and Stargardt disease, are ongoing or recently completed. Transplantation of limbal epithelial stem cells for treatment of their deficiency is the first cell therapy for ocular diseases in clinical practice. Patients enrolled in clinical trials have observed benefits which provide proof of feasibility of treating damaged eyes. Although challenges still exist in the treatment of eye diseases, the improved vision of the treated patients are very encouraging. Development of gene and cell therapies for eye diseases is a hotly pursued field.

LCA is a rare disease that can be caused by one of 15 genetically changed genes, such as the retinal protein RPE65 that is crucial for visual stimulation from the retina to the brain. Although the protein does not maintain its function, the retinal cells remain alive and wired into the optic nerve for sight. Twelve patients with defective RPE65 were treated by gene therapy to correct this genetic defect in a phase I clinical trial. They were administered a low, medium or high dose of a viral vector that could produce the normal RPE65 protein in the retina of afflicted patients. Treated patients showed at least a 100-fold improvement in light sensitivity for the length of the study (up to 2 years) [Lancet. 2009 Nov 7;374(9701):1597-605]. Remarkably, in another trial, at least a 64,000-fold recovery in local light sensitivity was shown in one patient that was treated, and every patient analyzed in the same trial has gained more than a 100-fold improvement thus far (Cideciyan, et al, PNAS 105:15112). As Maquire et al wrote, “all patients showed improvement in …vision” including improved walking ability around objects. Children had the most improvement. This trial acts as a proof of concept or proof of feasibility for treating genetic eye diseases with gene therapy. Studies in large animals are investigating the safety profile of treating the second eye of patients with LCA.

Stargardt disease is the most common form of inherited juvenile macular degeneration that begins in late childhood and lead to legal blindness. The mutations are in a gene called ABCA4 responsible for the majority of Stargardt disease children. In November 2010, the FDA approved a Phase I/II multicenter clinical trial using retinal cells derived from human embryonic stem cells (hESCs) to treat patients with Stargardt’s Macular Dystrophy (SMD).

Scientists and clinicians are also interested in treating other hereditary and non-hereditary eye diseases. In some eye diseases, different cell populations, including the retinal cells, rods, cones or limbal epithelial stem cells atrophy or die. Thus, stem cells or stem cells expressing the corrected/normal gene would be needed because of the lack of intact cells. For example, limbal epithelial stem cells can also die by exposure to chemicals and their deficiency causes pain, light sensitivity, and cloudy vision. Transplantation of limbal epithelial stem cells for treatment of this deficiency is the first cell therapy for ocular diseases in clinical practice. These human studies provide proof of feasibility of replacing damaged or lost cells in the eye with stem cell therapy. Although challenges still exist in the treatment of eye diseases, the improved vision of some of the treated patients are very encouraging.

Click here to read an interview on the New York Times, published on September 21, 2011, titled, "Experimental Treatment for Macular Degeneration."

For more information on congenital blindness and eye diseases, please visit the following websites:

Foundation Fighting Blindness
Foundation for Retinal Research

Genetic and Rare Diseases Information Center (GARD)
National Eye Institute