Fundus autofluorescence and ellipsoid zone (EZ) line width can be an outcome measurement in RHO-associated autosomal dominant retinitis pigmentosa
- 18 Downloads
To evaluate the progression of retinitis pigmentosa (RP) due to mutations in rhodopsin (RHO) by measuring the short-wavelength autofluorescence (SW-AF) increased autofluorescence ring and ellipsoid zone (EZ)-line width.
Fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) images were obtained from 10 patients with autosomal dominant RP due to mutations in the RHO gene. Measurements of ring area on FAF images, as well as the EZ line width on SD-OCT images and horizontal, vertical diameter, were performed by two independent masked graders.
The ring area decreased by a rate of 0.6 ± 0.2 mm2 per year. We observed that the EZ line width decreased by an average of 152 ± 37 μm per year, while the horizontal and vertical diameters decreased by 106 ± 35 μm and 125 ± 29 μm per year, respectively. Progression rates were similar between eyes.
We observed SW-AF ring constriction and a progressive loss of EZ line width over time.
KeywordsRetinitis pigmentosa RHO Autosomal dominant Disease progression
The Jonas Children’s Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory are supported by the National Institutes of Health [P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437], National Cancer Institute Core [5P30CA013696], Foundation Fighting Blindness [TA-NMT-0116-0692-COLU], the Research to Prevent Blindness (RPB) Physician-Scientist Award, and unrestricted funds from RPB, New York, NY, USA. S.H.T. is a member of the RD-CURE Consortium and is supported by ARVO/Genentech, Kobi and Nancy Karp, the Crowley Family Fund, the Rosenbaum Family Foundation, the Tistou and Charlotte Kerstan Foundation, the Schneeweiss Stem Cell Fund, New York State [C029572], and the Gebroe Family Foundation.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Boughman JA, Conneally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32:223–235Google Scholar
- 3.Sullivan LS, Bowne SJ, Birch DG et al (2006) Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families. Investig Ophthalmol Vis Sci. https://doi.org/10.1167/iovs.05-1443
- 4.Tsang SH (2006) GAP-independent termination of photoreceptor light response by excess subunit of the cGMP-phosphodiesterase. J Neurosci. https://doi.org/10.1523/JNEUROSCI.4775-05.2006
- 5.Woodruff ML, Janisch KM, Peshenko IV et al (2008) Modulation of phosphodiesterase6 turnoff during background illumination in mouse rod photoreceptors. J Neurosci. https://doi.org/10.1523/JNEUROSCI.2973-07.2008
- 6.Janz JM, Fay JF, Farrens DL (2003) Stability of dark state rhodopsin is mediated by a conserved ion pair in intradiscal loop E-2. J Biol Chem. https://doi.org/10.1074/jbc.M210567200
- 7.Yan ECY, Kazmi MA, Ganim Z et al (2003) Retinal counterion switch in the photoactivation of the G protein-coupled receptor rhodopsin. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.1531970100
- 8.Tsang SH, Burns ME, Calvert PD et al (1998) Role for the target enzyme in deactivation of photoreceptor G protein in vivo. Science (80- ). https://doi.org/10.1126/science.282.5386.117
- 9.Woodruff ML, Wang Z, Chung HY et al (2003) Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis. Nat Genet. https://doi.org/10.1038/ng1246
- 12.Sancho-Pelluz J, Tosi J, Hsu C-W et al (2012) Mice with a D190N mutation in the gene encoding rhodopsin: a model for human autosomal-dominant retinitis pigmentosa. Mol Med. https://doi.org/10.2119/molmed.2011.00475
- 14.Robson AG, Saihan Z, Jenkins SA et al (2006) Functional characterisation and serial imaging of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Br J Ophthalmol. https://doi.org/10.1136/bjo.2005.082487
- 16.Robson AG, Tufail A, Fitzke F et al (2011) Serial imaging and structure-function correlates of high-density rings of fundus autofluorescence in retinitis pigmentosa. Retina. https://doi.org/10.1097/IAE.0b013e318206d155
- 20.Kremmer S (1997) Ocular findings in patients with autosomal dominant retinitis pigmentosa and Cys110Phe, Arg135Gly, and Gln344stop mutations of rhodopsin. Graefes Arch Clin Exp Ophthalmol. https://doi.org/10.1007/BF00947087
- 25.Tsai Y-T, Wu W-H, Lee T-T et al (2018) Clustered regularly interspaced short palindromic repeats-based genome surgery for the treatment of autosomal dominant retinitis pigmentosa. Ophthalmology. https://doi.org/10.1016/j.ophtha.2018.04.001
- 27.Latella MC, Di Salvo MT, Cocchiarella F et al (2016) In vivo editing of the human mutant rhodopsin gene by electroporation of plasmid-based CRISPR/Cas9 in the mouse retina. Mol Ther - Nucleic Acids. https://doi.org/10.1038/mtna.2016.92
- 28.Mao H, Gorbatyuk MS, Rossmiller B et al (2012) Long-term rescue of retinal structure and function by rhodopsin RNA replacement with a single adeno-associated viral vector in P23H RHO transgenic mice. Hum Gene Ther. https://doi.org/10.1089/hum.2011.213
- 29.Bassuk AG, Zheng A, Li Y et al (2016) Precision medicine: genetic repair of retinitis pigmentosa in patient-derived stem cells. Sci Rep. https://doi.org/10.1038/srep19969
- 30.Sujirakul T, Davis R, Erol D et al (2015) Bilateral concordance of the fundus hyperautofluorescent ring in typical retinitis pigmentosa patients. Ophthalmic Genet. https://doi.org/10.3109/13816810.2013.841962
- 31.Iriyama A, Yanagi Y (2012) Fundus autofluorescence and retinal structure as determined by spectral domain optical coherence tomography, and retinal function in retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol. https://doi.org/10.1007/s00417-011-1823-5