Abstract
Retinitis pigmentosa (RP) is a group of genetic disorders resulting in inherited blindness due to the degeneration of rod and cone photoreceptors. The various mechanisms underlying rod degeneration primarily rely on genetic mutations, leading to night blindness initially. Cones gradually degenerate after rods are almost eliminated, resulting in varying degrees of visual disability and blindness. The mechanism of cone degeneration remains unclear. An understanding of the mechanisms underlying cone degeneration in RP, a highly heterogeneous disease, is essential to develop novel treatments of RP. Herein, we review recent advancements in the five hypotheses of cone degeneration, including oxidative stress, trophic factors, metabolic stress, light damage, and inflammation activation. We also discuss the connection among these theories to provide a better understanding of secondary cone degeneration in RP.
Graphical Abstract
Five current mechanisms of cone degenerations in RP Interactions among different pathways are involved in RP.
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Data Availability
Enquiries about data availability should be directed to the authors.
Abbreviations
- BSG1:
-
Basigin-1
- CNTF:
-
Ciliary neurotrophic factor
- CR3:
-
Complement receptor 3
- CRALBP:
-
Cellular retinaldehyde-binding protein
- CX3CL1:
-
Fractalkine
- ERG:
-
Photopic electroretinography
- GDNF:
-
Glial cell line-derived neurotrophic factor
- GLUT1:
-
Glucose transporter
- mTOR:
-
Mammalian target of rapamycin
- NOXs:
-
NADPH oxidases
- ONL:
-
Outer nuclear layer
- PI3K:
-
Phosphoinositide 3 kinase
- RdCVF:
-
Rod-derived cone viability factor
- RGR:
-
RPE-retinal G protein-coupled receptor
- RHO:
-
Rhodopsin
- ROS:
-
Reactive oxygen species
- RP:
-
Retinitis pigmentosa
- RPE:
-
Retinal pigment epithelial
- RPE65:
-
RPE-specific 65 kDa protein
- SOD:
-
Superoxide dismutase
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We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
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This work was supported by grants from the National Natural Science Foundation of China (No. 82171053 and No. 81570864) and the Natural Science Foundation of Jilin Province (No. 20200801043GH and No. 20190201083JC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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All authors contributed to the study conception and design. DJS and XLB designed and wrote the initial manuscript. BF and GYL made the revision. All authors read and approved the final manuscript.
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Song, DJ., Bao, XL., Fan, B. et al. Mechanism of Cone Degeneration in Retinitis Pigmentosa. Cell Mol Neurobiol 43, 1037–1048 (2023). https://doi.org/10.1007/s10571-022-01243-2
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DOI: https://doi.org/10.1007/s10571-022-01243-2