Research progress of cyclic guanosine monophosphate in inherited retinal degeneration_Chinese Journal of Ocular Fundus Diseases

Authors：

Liu Zishi ,  Li Tong , Sun Xiaodong

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Ophthalmic Diseases, Shanghai Key Laboratory of Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China;

Corresponding author：

Li Tong, Email: litong_linda@outlook.com

Keywords：

Inherited retinal degeneration; Cyclic guanosine monophosphate; Phototransduction; Review

DOI：

10.3760/cma.j.cn511434-20240701-00246

Video：

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Abstract Full text Figures/Tables Video References Cited by

Inherited retinal degeneration (IRD) is a group of fundus diseases characterized by a high degree of genetic heterogeneity and clinical heterogeneity, and more than 300 genetic mutations have been identified in association with IRD. Dysregulation of the intracellular second messenger cyclic guanosine monophosphate (cGMP) plays an important role in the development of IRD. cGMP participates in phototransduction process in photoreceptors. Abnormally elevated cGMP over-activate protein kinase G and cyclic nucleotide-gated channel, causing protein phosphorylation and Ca²⁺ overload, respectively, and these two cGMP-dependent pathways may individually or collectively drive photoreceptor degenerative lesions and death; therefore, reducing cGMP synthesis and blocking downstream signaling can be considered as treatment strategies. Investigating the molecular mechanisms of cGMP dysregulation in photoreceptor degeneration may provide a more comprehensive picture of the pathogenesis of IRD, as well as ideas for finding new therapeutic targets and designing therapeutic programs.

Citation： Liu Zishi, Li Tong, Sun Xiaodong. Research progress of cyclic guanosine monophosphate in inherited retinal degeneration. Chinese Journal of Ocular Fundus Diseases, 2024, 40(11): 898-904. doi: 10.3760/cma.j.cn511434-20240701-00246 Copy

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1. Arango-Gonzalez B, Trifunovic D, Sahaboglu A, et al. Identification of a common non-apoptotic cell death mechanism in hereditary retinal degeneration[J/OL]. PLoS One, 2014, 9(11): e112142[2014-11-13]. https://www.ncbi.nlm.nih.gov/pubmed/25392995/. DOI: 10.1371/journal.pone.0112142.
2. Vighi E, Trifunovic D, Veiga-Crespo P, et al. Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration[J/OL]. Proc Natl Acad Sci USA, 2018, 115(13): E2997-3006[2018-03-12]. https://www.ncbi.nlm.nih.gov/pubmed/29531030/. DOI: 10.1073/pnas.1718792115.
3. Paquet-Durand F, Marigo V, Ekstrom P. RD genes associated with high photoreceptor cGMP-levels (mini-review)[J]. Adv Exp Med Biol, 2019, 1185: 245-249. DOI: 10.1007/978-3-030-27378-1_40.
4. Friebe A, Sandner P, Schmidtko A. cGMP: a unique 2nd messenger molecule-recent developments in cGMP research and development[J]. Naunyn Schmiedebergs Arch Pharmacol, 2020, 393(2): 287-302. DOI: 10.1007/s00210-019-01779-z.
5. Tucker CL, Woodcock SC, Kelsell RE, et al. Biochemical analysis of a dimerization domain mutation in RetGC-1 associated with dominant cone-rod dystrophy[J]. Proc Natl Acad Sci USA, 1999, 96(16): 9039-9044. DOI: 10.1073/pnas.96.16.9039.
6. Dell'orco D, Schmidt H, Mariani S, et al. Network-level analysis of light adaptation in rod cells under normal and altered conditions[J]. Mol Biosyst, 2009, 5(10): 1232-1246. DOI: 10.1039/b908123b.
7. Pugh EN Jr, Lamb TD. Cyclic GMP and calcium: the internal messengers of excitation and adaptation in vertebrate photoreceptors[J]. Vision Res, 1990, 30(12): 1923-1948. DOI: 10.1016/0042-6989(90)90013-b.
8. Ebrey T, Koutalos Y. Vertebrate photoreceptors[J]. Prog Retin Eye Res, 2001, 20(1): 49-94. DOI: 10.1016/s1350-9462(00)00014-8.
9. Hagins WA, Penn RD, Yoshikami S. Dark current and photocurrent in retinal rods[J]. Biophys J, 1970, 10(5): 380-412. DOI: 10.1016/S0006-3495(70)86308-1.
10. Den Hollander AI, Roepman R, Koenekoop RK, et al. Leber congenital amaurosis: genes, proteins and disease mechanisms[J]. Prog Retin Eye Res, 2008, 27(4): 391-419. DOI: 10.1016/j.preteyeres.2008.05.003.
11. Gill JS, Georgiou M, Kalitzeos A, et al. Progressive cone and cone-rod dystrophies: clinical features, molecular genetics and prospects for therapy[J]. Br J Ophthalmol, 2019, 103(5): 711-720. DOI: 10.1136/bjophthalmol-2018-313278.
12. Sato M, Nakazawa M, Usui T, et al. Mutations in the gene coding for guanylate cyclase-activating protein 2 (GUCA1B gene) in patients with autosomal dominant retinal dystrophies[J]. Graefe's Arch Clin Exp Ophthalmol, 2005, 243(3): 235-242. DOI: 10.1007/s00417-004-1015-7.
13. Li Y, Wang H, Peng J, et al. Mutation survey of known LCA genes and loci in the Saudi Arabian population[J]. Invest Ophthalmol Vis Sci, 2009, 50(3): 1336-1343. DOI: 10.1167/iovs.08-2589.
14. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa[J]. Lancet, 2006, 368(9549): 1795-1809. DOI: 10.1016/S0140-6736(06)69740-7.
15. Power M, Das S, Schutze K, et al. Cellular mechanisms of hereditary photoreceptor degeneration-focus on cGMP[J/OL]. Prog Retin Eye Res, 2020, 74: 100772[2019-07-30]. https://pubmed.ncbi.nlm.nih.gov/31374251/. DOI: 10.1016/j.preteyeres.2019.07.005.
16. Weisschuh N, Stingl K, Audo I, et al. Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia[J]. Hum Mutat, 2018, 39(10): 1366-1371. DOI: 10.1002/humu.23606.
17. Kohl S, Coppieters F, Meire F, et al. A nonsense mutation in PDE6H causes autosomal-recessive incomplete achromatopsia[J]. Am J Hum Genet, 2012, 91(3): 527-532. DOI: 10.1016/j.ajhg.2012.07.006.
18. Sohocki MM, Perrault I, Leroy BP, et al. Prevalence of AIPL1 mutations in inherited retinal degenerative disease[J]. Mol Genet Metab, 2000, 70(2): 142-150. DOI: 10.1006/mgme.2000.3001.
19. Méjécase C, Laurent-Coriat C, Mayer C, et al. Identification of a novel homozygous nonsense mutation confirms the implication of GNAT1 in rod-cone dystrophy[J/OL]. PLoS One, 2016, 11(12): e0168271[2016-12-15]. https://www.ncbi.nlm.nih.gov/pubmed/27977773/. DOI: 10.1371/journal.pone.0168271.
20. Carrigan M, Duignan E, Humphries P, et al. A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration[J]. Br J Ophthalmol, 2016, 100(4): 495-500. DOI: 10.1136/bjophthalmol-2015-306939.
21. Felden J, Baumann B, Ali M, et al. Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene[J]. Hum Mutat, 2019, 40(8): 1145-1155. DOI: 10.1002/humu.23768.
22. Wissinger B, Gamer D, Jägle H, et al. CNGA3 mutations in hereditary cone photoreceptor disorders[J]. Am J Hum Genet, 2001, 69(4): 722-737. DOI: 10.1086/323613.
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