In a review published in the 10th Anniversary Series of Science Translational Medicine, it was depicted that advances in preclinical research are now being translated into an innovative clinical solution for blindness. Authored by Jose Sahel, Jean Bennett, and Botond Roska, the review summarizes new therapeutic strategies for treating blinding diseases which are quite encouraging.
Apart from reversing vision loss, gene replacement, or gene editing strategies could lead to close to typical visual outcomes. Early intervention during the early stages of retinal degeneration when the photoreceptor cells (rods and cones) are still intact, is particularly promising. The first approved gene therapy for Leber congenital amaurosis (LCA) with confirmed biallelic RPE65 mutations such as those in clinical phase III for choroideremia, achromatopsia, and Leber hereditary optic neuropathy.
Gene-independent aims to prevent or slow the progressive degeneration of photoreceptor cells with neuroprotective agents for a broad spectrum of retinal dystrophies. Neuroprotective strategies, particularly those for preserving cones, are the best approach for treating disease where there is ongoing photoreceptor cell degeneration.
Scientists use stem cell therapy, optogenetic therapy, and retinal prostheses to restore vision during the later stages of retinal degeneration. It is possible to apply these approaches independently of the causal mutation and is expected to restore a low degree of vision in blind patients.
Stem cells therapies to replace degenerated cells for restoring vision are under development or clinical evaluation in a broader range of retinal degenerative conditions such as the "non-neovascular" form (associated with gradual loss of photoreceptors and RPE cells) of age-related macular degeneration (AMD), for inherited retinal dystrophies (IRDs) and retinal pigment epithelium (RPE) replacement.
Brain-machine interface technologies using electrode arrays or optogenetics can stimulate the visual pathway downstream of the retina. Electrical stimulation of the primary visual cortex is one possible scenario that is currently in clinical trials.
Cells are light sensitive through optogenetic therapy with the expression of an optogenetic encoding a light-activated channel or pump in the remaining inner retinal cells. It could be used to resensitize a degenerated retina to visible light independent of the mutation causing photoreceptor cells loss.
There is a potential for retinal prostheses to reactivate remaining retinal circuits at the level of bipolar or ganglion cells after photoreceptor cell loss. Both epiretinal and subretinal implants can stimulate a light-insensitive degenerated retina and restore partial vision in blind individuals.
Specific qualities make the eye particularly suited for diagnostic and therapeutic exploration; easy access, small volume, high internal compartmentalization, and stable cells explorations. The optical transparency of the eye allows direct visualization with high-resolution imaging and precise evaluation of disease stage and response to therapy.
The relative immune privilege of the eye, especially the subretinal space, reduces adverse responses to injected vectors and gene products. Progress in ophthalmology, however, is intrinsically connected to increased understanding of the morphology and function of the visual system.
