Introduction : l'Initiative Lasker

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The notion that restoring vision to the blind is possible has long been thought to be fanciful. However, beginning as far back as the 1960’s vision scientists began to investigate the possibility of restoring vision to the blind by activating neurons in the visual pathways beyond the eye, namely in the visual cortex. In recent years, a number of approaches have been undertaken to restore vision to the blind. The major cause of untreatable blindness is retinal degenerative disease, most often because of a loss of photoreceptor cells. Much emphasis in the quest to cure blindness is to restore photoreceptive function in blind eyes, or to substitute for the loss of photoreceptor function. Most success so far has come from two approaches. First, retinal prostheses have been developed that electrically stimulate the second or third order retinal neurons, namely the retinal bipolar or ganglion cells. The second approach is gene therapy, injecting a viral construct containing the normal gene into the eye, thus replacing the defective gene. A newer approach is a combination of the above two approaches, namely imparting light sensitivity to retinal neurons via genetic means called optogenetics. Genes that code for light-sensitive molecules are introduced into various retinal cells, most often bipolar or ganglion cells. Another approach is to replace damaged photoreceptor cells by transplanting healthy photoreceptor cells into the eyes of blind animals. Stem cells, which in theory can differentiate into any cell type, have also been introduced into blind eyes. Investigators are now inducing stem cells maintained in culture to differentiate into photoreceptor cells and then are injecting such cells into eyes, and this approach appears promising. Nonmammalian species, including amphibians and fish, can regenerate all retinal cell types endogenously, but mammals cannot. Why cold-blooded vertebrates can do this is an intriguing question that is now receiving substantial attention. The cells involved appear to be Muller (glial) cells and the retinal pigment epithelium, which act like stem cells.

The objective of the Lasker/IRRF initiative was to evaluate the various approaches presently underway, to identify the most promising and feasible approaches and to indicate the major problems and issues that must be overcome to make an approach useful and effective. In addition to the above, other topics were considered that may impact the approaches being taken. For example, the retinal prostheses that have been developed so far provide only low-level vision. Devices have been developed over the years to help those who are visually impaired. Can these devices be of use to those who have low vision restored as a result of an implanted visual prosthesis? Another area considered was neuroprotection, neuroactive substances that protect neurons and slow down degeneration. Can such molecules be used in conjunction with other restorative approaches to enhance effectiveness? A final topic was that of end points—what is the best way to measure the return of visual function in previously blind patients? The gold standard to evaluate vision ordinarily is visual acuity—but there is much more to vision than just acuity.