Abstract
Spectral domain optical coherence tomography (SD-OCT) has recently been established as a method for in vivo imaging of fundus and retina in the mouse. It enables more effective studies of retinal diseases including investigations of etiopathologic mechanisms. In order to learn more about longitudinal fundus development and to enable recognition of disease-associated irregularities, we performed confocal scanning laser ophthalmoscopy (cSLO) and SD-OCT measurements in the inbred strains C57BL/6J, C3HeB/FeJ, FVB/NCrl, BALB/cByJ, and 129S2/SvJ when they were between 2 and 6 months of age. In general, cSLO and SD-OCT data did not reveal sex-specific or unilateral differences. C3HeB/FeJ and FVB/NCrl mice showed diffuse choroidal dysplasia. Choroidal vein-like structures appeared as dark fundus stripes in C3HeB/FeJ. In FVB/NCrl, fundus fleck accumulation was found. In contrast, only minor time-dependent changes of fundus appearance were observed in C57BL/6J, BALB/cByJ, and 129S2/SvJ. This was also found for individual fundic main blood vessel patterns in all inbred strains. Vessel numbers varied between 6 and 13 in C57BL/6J. This was comparable in most cases. We further found that retinae were significantly thicker in C57BL/6J compared to the other strains. Total retinal thickness generally did not change between 2 and 6 months of age. As a conclusion, our results indicate lifelong pathologic processes in C3HeB/FeJ and FVB/NCrl that affect choroid and orbital tissues. Inbred strains with regular retinal development did not reveal major time-dependent variations of fundus appearance, blood vessel pattern, or retinal thickness. Consequently, progressive changes of these parameters are suitable indicators for pathologic outliers.






Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.References
Ahmed ZM, Riazuddin S, Riazuddin S, Wilcox ER (2003) The molecular genetics of Usher syndrome. Clin Genet 63:431–444
Ashery-Padan R (2002) Somatic gene targeting in the developing and adult mouse retina. Methods 28:457–464
Bell BA, Kaul C, Rayborn ME, Hollyfield JG (2012) Baseline imaging reveals preexisting retinal abnormalities in mice. Adv Exp Med Biol 723:459–469
Brilliant MH (2001) The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH. Pigment Cell Res 14:86–93
Chang B, Hawes NL, Hurd RE, Davisson MT, Nusinowitz S, Heckenlively JR (2002) Retinal degeneration mutants in the mouse. Vis Res 42:517–525
Chou TH, Kocaoglu OP, Borja D, Ruggeri M, Uhlhorn SR, Manns F, Porciatti V (2011) Postnatal elongation of eye size in DBA/2J mice compared with C57BL/6J mice: in vivo analysis with whole-eye OCT. Invest Ophthalmol Vis Sci 52:3604–3612
Dalke C, Graw J (2005) Mouse mutants as models for congenital retinal disorders. Exp Eye Res 81:503–512
Dalke C, Löster J, Fuchs H, Gailus-Durner V, Soewarto D, Favor J, Neuhäuser-Klaus A, Pretsch W, Gekeler F, Shinoda K, Zrenner E, Meitinger T, Hrabé de Angelis M, Graw J (2004) Electroretinography as a screening method for mutations causing retinal dysfunction in mice. Invest Ophthalmol Vis Sci 45:601–609
Fischer MD, Huber G, Beck SC, Tanimoto NT, Muehlfriedel R, Fahl E, Grimm C, Wenzel A, Remé CE, van de Pavert SA, Wijnholds J, Pacal M, Bremner R, Seeliger MW (2009) Noninvasive, in vivo assessment of mouse retinal structure using optical coherence tomography. PLoS One 4:e7507
Fischer MD, Huber G, Paquet-Durand F, Humphries P, Redmond TM, Grimm C, Seeliger MW (2012) In vivo assessment of rodent retinal structure using spectral domain optical coherence tomography. Adv Exp Med Biol 723:489–494
Fuchs H, Gailus-Durner V, Neschen S, Adler T, Afonso LC, Aguilar-Pimentel JA et al (2012) Innovations in phenotyping of mouse models in the German Mouse Clinic. Mamm Genome 23:611–622
Hawes NL, Smith RS, Chang B, Davisson M, Heckenlively JR, John SW (1999) Mouse fundus photography and angiography: a catalogue of normal and mutant phenotypes. Mol Vis 5:22
Hoerster R, Muether PS, Vierkotten S, Schröder S, Kirchhof B, Fauser S (2012) In-vivo and ex vivo characterization of laser-induced choroidal neovascularization variability in mice. Graefes Arch Clin Exp Ophthalmol 250:1579–1586
Huber G, Beck SC, Grimm C, Sahaboglu-Tekgoz A, Paquet-Durand F, Wenzel A, Humphries P, Redmond TM, Seeliger MW, Fischer MD (2009) Spectral domain optical coherence tomography in mouse models of retinal degeneration. Invest Ophthalmol Vis Sci 50:5888–5895
Johnson KR, Zheng QY, Noben-Trauth K (2006) Strain background effects and genetic modifiers of hearing in mice. Brain Res 1091:79–88
Kang TH, Ryu YH, Kim IB, Oh GT, Chun MH (2004) Comparative study of cholinergic cells in retinas of various mouse strains. Cell Tissue Res 317:109–115
Knott EJ, Sheets KG, Zhou Y, Gordon WC, Bazan NG (2011) Spatial correlation of mouse photoreceptor-RPE thickness between SD-OCT and histology. Exp Eye Res 92:155–160
Naash MI, Ripps H, Li S, Goto Y, Peachey NS (1996) Polygenic disease and retinitis pigmentosa: albinism exacerbates photoreceptor degeneration induced by the expression of a mutant opsin in transgenic mice. J Neurosci 16:7853–7858
Nagpal K, Nagpal M, Narendra GV, Nagpal PN (2004) Optical coherence tomography. J Bombay Ophthalmol Assoc 13:4–10
Puk O, Dalke C, Favor J, Hrabé de Angelis MH, Graw J (2006) Variations of eye size parameters among different strains of mice. Mamm Genome 17:851–857
Puk O, Dalke C, Hrabé de Angelis M, Graw J (2008) Variation of the response to the optokinetic drum among various strains of mice. Front Biosci 13:6269–6275
Rao A, Padhi TR, Jena S, Mandal S, Das T (2012) Atypical features of nanophthalmic macula—a spectral domain OCT study. BMC Ophthalmol 12:12
Schraermeyer U, Heimann K (1999) Current understanding on the role of retinal pigment epithelium and its pigmentation. Pigment Cell Res 12:219–236
Secondi R, Kong J, Blonska AM, Staurenghi G, Sparrow JR (2012) Fundus autofluorescence findings in a mouse model of retinal detachment. Invest Ophthalmol Vis Sci 53:5190–5197
Shibahara S, Okinaga S, Tomita Y, Takeda A, Yamamoto H, Sato M, Takeuchi T (1990) A point mutation in the tyrosinase gene of BALB/c albino mouse causing the cysteine → serine substitution at position 85. Eur J Biochem 189:455–461
Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia A, McInnes RR, van der Kooy D (2000) Retina stem cells in the adult mammalian eye. Science 287:2032–2036
Yeritsyan N, Lehmann K, Puk O, Graw J, Löwel S (2012) Visual capabilities and cortical maps in BALB/c mice. Eur J Neurosci 36:2801–2811
Acknowledgments
We thank Erika Bürkle, Maria Kugler, and Nadine Senger for expert technical assistance and Lillian Garrett for critical reading of the manuscript. This work was supported by National Genome Network Grant NGFN-Plus (BMBF 01GS0850), Infrafrontier (Grants BMBF 01KX1011 and BMBF 01KX1012), and EUMODIC (European Mouse Disease Clinic; Grant LSHG-2006-037188).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Puk, O., de Angelis, M.H. & Graw, J. Longitudinal fundus and retinal studies with SD-OCT: a comparison of five mouse inbred strains. Mamm Genome 24, 198–205 (2013). https://doi.org/10.1007/s00335-013-9457-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00335-013-9457-z

