Treatment modalities

Recent developments include therapeutic modalities associated with gene therapy aimed at correcting various specific mutations, cell transplantation to replace lost cells, pharmacologic options to help preserve photoreceptors and the use of neuroprosthetic devices to generate visual perception.

Gene therapy

Gene therapy aims at correcting various specific disease-causing mutations. By replacing or turning off the mutated gene, healthy genes can be inserted into the retina to restore the protein function. Different gene-mediated therapeutic strategies have been developed using either viral or non-viral vectors. The large number of genes however and the dominant inheritance of many types of RP are major challenges for the corrective gene therapy.

In mutations leading to loss of function (arRP or X-linked recessive retinal degenerations), the principle of gene therapy is to correct the genetic defect by the introduction of a wild-type version of the mutated gene into the cells in which normal functioning of this gene is required (photoreceptors or RPE cells). One notable gene-replacement approach targets the RPE65 gene.

Dominantly inherited mutations typically alter the transcribed aminoacid sequence and result in toxic variants of the encoded protein (gain-of-function or dominant-negative mutations). One strategy to treat these alterations is to eliminate the mutant gene (gene silencing). The remaining normal copy of the gene is expected to provide sufficient functional protein. Current experimental approaches used in autosomal dominant conditions include ribozyme-based or interference RNA (RNAi)-based gene therapy.

Gene therapy approaches have experimentally been shown to delay and reverse the course of RP, with associated improvement of photoreceptor function in various animal models. Long-term efficacy and safety of the gene therapy still needs to be established

Trophic factors

Neurotrophic factors such as basic fibroblast growth factors (bFGF or FGF-2) and ciliary neurotrophic factors (CNTF) are currently under investigation as therapeutic modalities in RP. It has been shown that FGF-2 exerts both histologic and functional rescue on degenerating photoreceptors. However, it also triggers pathological retinal neovascularization, which makes it unacceptable for human therapy. CNTF has been found to slow retinal degeneration in a number of animal models. Clinical studies have reported evidence of retinal thickening and measurable visual improvement after one year of treatment with CNTF. However, paradoxical decrease in both scotopic and photopic responses in CNTF-treated retina has also been described, leading to evaluation of other trophic factors. Among them, glial cell line-derived neurotrophic factor (GDNF), has been found to slow down the rod degeneration and preserve visual function.

Prevention the secondary degeneration of cones in RP represents a very promising approach. This because such a therapy could be applied in a wide range of mutations expressed in rods, and even at late stages of the disease. Rod-derived cone viability factor (RdCVF) has recently been shown to induce cone survival directly and to increase the cone numbers. Functional rescue and increased ERG-wave amplitudes have been documented. RdCVF trophic effects appear independent from the mechanisms and extent of rod degeneration that is one of the main advantages of this approach.

Neuroprosthetic devices

In RP, prosthesis can be designed to take over the function of the lost photoreceptors by electrical stimulation of the remaining healthy cells of the retina. Current implanted neuroprosthetic devices use optic nerve, retinal and cortical stimulation.

Optic nerve stimulation involves electrodes placed around the optic nerve, resulting in colored phosphenes throughout the visual field. By changing the duration and amplitude of the electrical stimulus, RP patients can perceive different levels of brightness of the generated phosphene.

Retinal stimulation includes both subretinal and epiretinal prostheses (phototransducing chip placed on the retinal surface). It consists of electrical current passing from individual electrodes that stimulate cells in the appropriate areas of the retina. At present, retinal prosthetics are still under clinical investigation and not available commercially.

Cortical stimulation (surface or intracortical stimulation) uses visual images captured by a camera that are collected on a computer base stimulator mounted on a pair of glasses. The main advantage of the cortical visual prosthesis is that it bypasses the damaged retina and directly stimulates the primary visual cortex. However, it is associated with increased risk of seizures. Low-resolution imaging, craniotomy-associated risks and the cost should be considered.

Visual prosthetics

The BrainPort vision device is a non-surgical assistive visual prosthetic that translates information from a digital video camera to the tongue through gentle electrical stimulation. It consists of a base unit, a head-mounted camera, a hand-held controller, and an electrode array that sit on top of the tongue. The system collects visual information through the camera, send it instantaneously to the base unit, which converts it into an electrical pattern. The latter is then displayed on the tongue though the electrode array. A tactile "image" is then created using electrical stimulation.

Artificial human vision and other future modalities

Recently, technology transforming the auditory information into visual sensory information has been developed (vOICe). It uses an extraocular camera placed within sunglasses. Visual images from the camera are then mapped into sound, which the subject must decode into visual input (seeing with sound). Yet, no large clinical trials have been conducted to assess the capacities of this technology.

Speech recognition software, light-sensitive microchip implantation, wearable computers, satellite positioning and other emerging technologies have been invented and can help the individuals with RP in the future. It is still to be established whether patients with RP achieve useful vision with these devices. Since about 2001, people with vision impairment may have access to commercial GPS-based navigations systems.

Potential future therapies

Cell transplantation

Cell transplantation consists in re-infusing of healthy cells into a sick retina. It aims at producing more healthy cells to replace the nonfunctional cells. Two different strategies have been developed: RPE transplantation (that attempts to obtain beneficial effects upon the adjacent photoreceptors) and retinal neuronal transplantation (that attempts to replace lost photoreceptor cells). Today, two main sources of cells for transplantation are used, retinal and stem cells.

Retinal cell transplantation is the introduction of healthy photoreceptor cells into the host. The advantage of this method over stem cell transplantation is that the retinal cells integrate well into the retinal layers and express specific retinal cell markers. In stem cell transplantation, the patient receives healthy stem cells, which may begin producing normal retinal cells. The main advantage of the stem cells is that they have the potential to differentiate into any type of cells, including retinal neural cells. Both adult bone marrow-derived stem cells and embryonic stem cells are under investigation. Subjective and objective visual improvement has been documented in a number of subjects following this cell transplantation method


Some degree of vision may potentially be restored if remaining neurons could directly respond to light and transmit information to visual centers. Recently, light-sensitive cation channels (Channelrhodopsins) and anion pumps (Halorhodopsins) were shown to modulate the neural activity in response to visible light. All known Channelrhodopsins are unspecific cation channels, conducting H+, Na+, K+, and Ca2+ ions. By targeting these rhodopsins, a virtual ON or OFF signaling pathway may potentially be generated and a new technology for vision restoration proposed.