Optical Coherence Tomography of Animal Models of Retinitis Pigmentosa: From Animal Studies to Clinical Applications

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2019 Nov 30

PMID 31781647

Citations 13

Authors

Mitsuru Nakazawa

Aiko Hara

Sei-Ichi Ishiguro

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of this study was to understand the relationship between the findings of spectral-domain optical coherence tomography (SD-OCT) of previously reported animal models of retinitis pigmentosa (RP) associated with known genetic mutations and their background structural and functional changes.

Methods: We reviewed previous publications reporting the SD-OCT findings of animal models of RP and summarized the characteristic findings of SD-OCT in nine different animal models ( , P23H, S334ter, , , rp12, (rd1 and rd10), and ) of human RP.

Results: Despite the various abnormal structural changes found in these different animal models, progressive thinning of the outer nuclear layer (ONL) and hyperreflective change in the inner and outer segment (IS-OS) layers of the photoreceptors were commonly observed on SD-OCT. In the rapidly progressive severe photoreceptor degeneration seen in rd10 and mice, the ONL appeared hyperreflective. Electroretinography revealed various degrees of disease severity in these animal models. : SD-OCT is sensitive enough to detect even mild changes in the photoreceptor OS. Conversely, SD-OCT cannot qualitatively differentiate the pathologic and functional differences in the photoreceptors associated with different genetic abnormalities, with the exception of the rapid progression of severe forms of photoreceptor degeneration. These findings can be of value to understand better the clinical findings and the heterogeneous degenerative processes in patients with RP.

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References

Monai N, Yamauchi K, Tanabu R, Gonome T, Ishiguro S, Nakazawa M . Characterization of photoreceptor degeneration in the rhodopsin P23H transgenic rat line 2 using optical coherence tomography. PLoS One. 2018; 13(3):e0193778. PMC: 5844545. DOI: 10.1371/journal.pone.0193778. View

Cideciyan A, Jacobson S, Beltran W, Sumaroka A, Swider M, Iwabe S . Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci U S A. 2013; 110(6):E517-25. PMC: 3568385. DOI: 10.1073/pnas.1218933110. View

Trifunovic D, Sahaboglu A, Kaur J, Mencl S, Zrenner E, Ueffing M . Neuroprotective strategies for the treatment of inherited photoreceptor degeneration. Curr Mol Med. 2012; 12(5):598-612. DOI: 10.2174/156652412800620048. View

Chang B, Hawes N, Pardue M, German A, Hurd R, Davisson M . Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene. Vision Res. 2007; 47(5):624-33. PMC: 2562796. DOI: 10.1016/j.visres.2006.11.020. View

Sato K, Nakazawa M, Takeuchi K, Mizukoshi S, Ishiguro S . S-opsin protein is incompletely modified during N-glycan processing in Rpe65(-/-) mice. Exp Eye Res. 2010; 91(1):54-62. DOI: 10.1016/j.exer.2010.03.020. View

Pennesi M, Nishikawa S, Matthes M, Yasumura D, LaVail M . The relationship of photoreceptor degeneration to retinal vascular development and loss in mutant rhodopsin transgenic and RCS rats. Exp Eye Res. 2008; 87(6):561-70. PMC: 3541029. DOI: 10.1016/j.exer.2008.09.004. View

Yoon C, Yu H . The Structure-Function Relationship between Macular Morphology and Visual Function Analyzed by Optical Coherence Tomography in Retinitis Pigmentosa. J Ophthalmol. 2013; 2013:821460. PMC: 3866715. DOI: 10.1155/2013/821460. View

Lin J, LaVail M . Misfolded proteins and retinal dystrophies. Adv Exp Med Biol. 2010; 664:115-21. PMC: 2955894. DOI: 10.1007/978-1-4419-1399-9_14. View

Ikeda H, Sasaoka N, Koike M, Nakano N, Muraoka Y, Toda Y . Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa. Sci Rep. 2014; 4:5970. PMC: 4122966. DOI: 10.1038/srep05970. View

10.

Znoiko S, Rohrer B, Lu K, Lohr H, Crouch R, Ma J . Downregulation of cone-specific gene expression and degeneration of cone photoreceptors in the Rpe65-/- mouse at early ages. Invest Ophthalmol Vis Sci. 2005; 46(4):1473-9. DOI: 10.1167/iovs.04-0653. View

11.

Moreno M, Merida S, Bosch-Morell F, Miranda M, Villar V . Autophagy Dysfunction and Oxidative Stress, Two Related Mechanisms Implicated in Retinitis Pigmentosa. Front Physiol. 2018; 9:1008. PMC: 6070619. DOI: 10.3389/fphys.2018.01008. View

12.

Mizukoshi S, Nakazawa M, Sato K, Ozaki T, Metoki T, Ishiguro S . Activation of mitochondrial calpain and release of apoptosis-inducing factor from mitochondria in RCS rat retinal degeneration. Exp Eye Res. 2010; 91(3):353-61. DOI: 10.1016/j.exer.2010.06.004. View

13.

Marlhens F, Bareil C, Griffoin J, Zrenner E, AMALRIC P, Eliaou C . Mutations in RPE65 cause Leber's congenital amaurosis. Nat Genet. 1997; 17(2):139-41. DOI: 10.1038/ng1097-139. View

14.

Ruggeri M, Wehbe H, Jiao S, Gregori G, Jockovich M, Hackam A . In vivo three-dimensional high-resolution imaging of rodent retina with spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2007; 48(4):1808-14. DOI: 10.1167/iovs.06-0815. View

15.

Redmond T, Yu S, Lee E, Bok D, HAMASAKI D, Chen N . Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Nat Genet. 1998; 20(4):344-51. DOI: 10.1038/3813. View

16.

Dowling J, Sidman R . Inherited retinal dystrophy in the rat. J Cell Biol. 1962; 14:73-109. PMC: 2106090. DOI: 10.1083/jcb.14.1.73. View

17.

Sayo A, Ueno S, Kominami T, Okado S, Inooka D, Komori S . Significant Relationship of Visual Field Sensitivity in Central 10° to Thickness of Retinal Layers in Retinitis Pigmentosa. Invest Ophthalmol Vis Sci. 2018; 59(8):3469-3475. DOI: 10.1167/iovs.18-24635. View

18.

Sakami S, Kolesnikov A, Kefalov V, Palczewski K . P23H opsin knock-in mice reveal a novel step in retinal rod disc morphogenesis. Hum Mol Genet. 2013; 23(7):1723-41. PMC: 3943518. DOI: 10.1093/hmg/ddt561. View

19.

Toda K, Bush R, Humphries P, Sieving P . The electroretinogram of the rhodopsin knockout mouse. Vis Neurosci. 1999; 16(2):391-8. DOI: 10.1017/s0952523899162187. View

20.

Orhan E, Dalkara D, Neuille M, Lechauve C, Michiels C, Picaud S . Genotypic and phenotypic characterization of P23H line 1 rat model. PLoS One. 2015; 10(5):e0127319. PMC: 4444340. DOI: 10.1371/journal.pone.0127319. View