Salvaging Ruins: Reverting Blind Retinas into Functional Visual Sensors

Abstract

Blindness is one of the most devastating conditions affecting the quality of life. Hereditary degenerative diseases, such as retinitis pigmentosa, are characterized by the progressive loss of photoreceptors, leading to complete blindness. No treatment is known, the current state-of-the-art of restoring vision are implanted electrode arrays. As a recently discovered alternative, optical neuromodulators, such as channelrhodopsin, allow new strategies for treating these diseases by imparting light-sensitivity onto the remaining retinal neurons after photoreceptor cell death. Retinal degeneration is a heterogeneous set of diseases with diverse secondary effects on the retinal circuitry. Successful treatment strategies have to take into account this diversity, as only the existing retinal hardware can serve as substrate for optogenetic intervention. The goal is to salvage the retinal ruins and to revert the leftover tissue into a functional visual sensor that operates as optimally as possible. Here, we discuss three different successful approaches that have been applied to degenerated mouse retina.

Pulse trains to percepts: the challenge of creating a perceptually intelligible world with sight recovery technologies

“…Although optogenetics and small molecule photoswitches can be targeted with varying degrees of cell specificity (e.g. to cones [44], ganglion cells [4,5,7,[12][13][14], bipolar ON cells [7,13,15], and even ganglion cell dendrites and soma [45]), none of the rstb.royalsocietypublishing.org Phil. Trans.…”

“…All three approaches are capable of producing very low vision in either animal models or humans (optogenetics: [4,7], prostheses: [8,[12][13][14][15], small molecule photoswitches: [16 -18]). However, these are early days: no approach to date has convincingly proved capable of reliably eliciting behavioural performance levels equivalent to that of human patients with, for example, finger counting levels of vision.…”

Retinal gene therapy: current progress and future prospects

“…In addition to being gene-independent, the advantage of this strategy is to restore visual function following loss of photoreceptor cells. While thoroughly reviewed elsewhere [146,147], optogenetics briefly works through expression of light-sensitive proteins in residual inner retinal cells, such as retinal ganglion cells or bipolar cells. Expression of channelrhodopsin-2 (ChR2) and halorhodopsin, ionotropic rhodopsins found in green algae and halobacteria, respond to light stimulation through conformational changes that cause opening of the channel and cell depolarization [146].…”

Inherited Retinal Disease Therapies Targeting Precursor Messenger Ribonucleic Acid

“…The first of these is most appropriate for patients who present with end stage disease where few photoreceptors remain and retinal function is restored through cell replacement therapy or bionic vision via retinal visual prosthesis implant. Recent studies have discussed the benefits and disadvantages of these approaches in animal models and human patients with retinitis pigmentosa and age-related macular degeneration as their last resort for restoring vision [11,12,13,14,15]. In contrast, the ultimate aim of neuro-preservation strategies is to rescue neurons involved in neurodegeneration or slow down the degenerative process.…”