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Review
.2022 Dec 7;20(1):572.
doi: 10.1186/s12967-022-03738-4.

Potential therapeutic strategies for photoreceptor degeneration: the path to restore vision

Affiliations
Review

Potential therapeutic strategies for photoreceptor degeneration: the path to restore vision

Fereshteh Karamali et al. J Transl Med..

Abstract

Photoreceptors (PRs), as the most abundant and light-sensing cells of the neuroretina, are responsible for converting light into electrical signals that can be interpreted by the brain. PR degeneration, including morphological and functional impairment of these cells, causes significant diminution of the retina's ability to detect light, with consequent loss of vision. Recent findings in ocular regenerative medicine have opened promising avenues to apply neuroprotective therapy, gene therapy, cell replacement therapy, and visual prostheses to the challenge of restoring vision. However, successful visual restoration in the clinical setting requires application of these therapeutic approaches at the appropriate stage of the retinal degeneration. In this review, firstly, we discuss the mechanisms of PR degeneration by focusing on the molecular mechanisms underlying cell death. Subsequently, innovations, recent developments, and promising treatments based on the stage of disorder progression are further explored. Then, the challenges to be addressed before implementation of these therapies in clinical practice are considered. Finally, potential solutions to overcome the current limitations of this growing research area are suggested. Overall, the majority of current treatment modalities are still at an early stage of development and require extensive additional studies, both pre-clinical and clinical, before full restoration of visual function in PR degeneration diseases can be realized.

© 2022. The Author(s).

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Progression of retinal degeneration. The healthy retina consists of five major classes of neurons: photoreceptors, bipolar cells, retinal ganglion cells, horizontal cells, and amacrine cells, as well as the non-neuronal pigment epithelium. The early, intermediate, advanced, and late-stage of the retinal degenerative process results in changes in the function and morphology of the retina over time. These changes include truncation of the outer segments of PRs, reduction in cell numbers due to cell degeneration and death, appearance of reactive glial cells, hypertrophy of Müller cells, migration of neuronal cells, translocation of amacrine and bipolar cells into other layers, deep synaptic change, cell death progresses, the absence of visual capacity, deterioration of blood-retinal barrier and disruption of RPE and Brunch's membrane. The current therapeutic approaches have also been presented for each degeneration phase
Fig. 2
Fig. 2
Schematic presentation of various routes for drug delivery to retina, including topical, intravitreal, systemic, and periocular and sub-retinal routes
Fig. 3
Fig. 3
Nanoparticle-based drug delivery systems. Common carrier-based drug delivery systems of therapeutic nanoparticles: nanosphere, liposome, nanomicelle, nanocapsule, dendrimer, hydrogel, and lipid nanoparticle
Fig. 4
Fig. 4
Different approaches for retinal regeneration. Current therapy methods have been categorized in neuroprotection, gene therapy, cell therapy, and visual prosthesis
Fig. 5
Fig. 5
visual cycle pathway. Schematic representation of the phototransduction cascade and the visual cycle. In the left, the outer segment of PR was surrounded by the microvilli of the RPE apical membrane. In close, the biochemical events of RPE/ PR interaction have been presented. Upon light absorption by 11-cis-retinal opsin (inactive rhodopsin), the 11-cis- retinal rapidly is photo-isomerized to all-trans-retinal to form activated rhodopsin which in turn activates the heterotrimeric G-protein transducin and initiates the downstream signaling
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