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

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. Graphical Abstract

Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK‐ULK1 signaling

“…Photoreceptor degeneration contributes to irreversible visual loss 30 ; however, its mechanism is unclear. Although existing treatment methods include gene therapy, 31 stem cell transplantation, and visual prosthesis, 32 their therapeutic effects are unsatisfactory. Therefore, clarifying the pathogenic mechanisms and identifying therapeutic targets are imperative.…”

The Clinical Findings, Pathogenic Variants, and Gene Therapy Qualifications Found in a Leber Congenital Amaurosis Phenotypic Spectrum Patient Cohort

“…As a result, downstream enzyme reactions in the phototransduction cascade are impaired, preventing neuronal signals from reaching the visual cortex. There is, perhaps, a link to improper vitamin A metabolism and photoreceptor degeneration [6].…”

Alleviation of Photoreceptor Degeneration Based on Fullerenols in rd1 Mice by Reversing Mitochondrial Dysfunction via Modulation of Mitochondrial DNA Transcription and Leakage

“…Typical abnormalities in the fundus include bone spicule pigmentation in the periphery and/or mid‐periphery of the retina, which emerges owing to the degeneration of photoreceptors. Despite the wide genetic heterogeneity, [ 2 ] RP shares a general pathological process, namely the non‐genetic biological oxidative stress, [ 3 ] caused by excessive accumulation of reactive oxygen species (ROS). As photoreceptors maintain vigorous energy metabolism, ROS are constantly generated and accumulate in the degenerating retina.…”