Retinal Thickness Normative Data in Wild-Type Mice Using Customized Miniature SD-OCT

Objective To report normative data for retinal thickness in wild-type C57BL/6 mouse utilizing a miniature SD-OCT system. Methods Thirty adult mice (range: 3–5 months) were anesthetized and secured into the Bioptigen Spectral Domain Ophthalmic Imaging System. Right eye SD-OCT images were standardized by centralizing the optic nerve head (ONH) prior to image acquisition. Global and quadrant total retinal thickness (TRT) values were measured from retinal nerve fiber layer to retinal pigment epithelial layer. Posterior segment analyses also included the outer retinal layer (ORL) and inner retinal layer (IRL). Further sublayer analyses of four layers from the ORL and three layers comprising the IRL were also performed. Results The overall mean±SD global TRT in a C57BL/6 mouse model was 204.41±5.19 µm. Quadrant mean TRT values were 204.85±5.81 µm inferiorly, 204.97±6.71 µm nasally, 205.08±5.44 µm temporally, and 202.74±4.85 µm superiorly. Mean±SD thickness for ORL, and IRL were 126.37±10.01 µm, and 107.03±10.98 µm respectively. The mean±SD estimates for the four layers of the ORL were 18.23±2.73 µm, 26.04±4.21 µm, 63.8±6.23 µm, and 19.22±4.34 µm. Mean±SD values for the three IRL sublayers were 27.82±4.04 µm, 59.62±6.66 µm and 19.12±3.71 µm. Conclusion This study established normative values for the total retinal thickness and sublayer thickness for the wild-type C57BL/6 mice. Moreover, it provides a standard of retinal morphology, in a commonly used animal model, for evaluating therapeutic interventions and retinal disease pathophysiology.

[1]  J. Duker,et al.  Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography. , 2005, Ophthalmology.

[2]  Y Zhao,et al.  Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Koulen,et al.  NORMATIVE DATA SET IDENTIFYING PROPERTIES OF THE MACULA ACROSS AGE GROUPS: Integration of Visual Function and Retinal Structure With Microperimetry and Spectral-Domain Optical Coherence Tomography , 2011, Retina.

[4]  S. Donovan,et al.  Retinal degeneration in Aipl1-deficient mice: a new genetic model of Leber congenital amaurosis. , 2004, Brain research. Molecular brain research.

[5]  R. Radu,et al.  Light exposure stimulates formation of A2E oxiranes in a mouse model of Stargardt's macular degeneration. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Lois E. H. Smith,et al.  Oxygen-induced retinopathy in the mouse. , 1994, Investigative ophthalmology & visual science.

[7]  J. Hurley,et al.  Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Michael I Dorrell,et al.  Chapter 6. Ocular models of angiogenesis. , 2008, Methods in enzymology.

[9]  D. Reitze,et al.  Noninvasive imaging by optical coherence tomography to monitor retinal degeneration in the mouse. , 2001, Investigative ophthalmology & visual science.

[10]  Andreas Wenzel,et al.  Noninvasive, In Vivo Assessment of Mouse Retinal Structure Using Optical Coherence Tomography , 2009, PloS one.

[11]  Andreas Wenzel,et al.  Spectral domain optical coherence tomography in mouse models of retinal degeneration. , 2009, Investigative ophthalmology & visual science.

[12]  Robert J Zawadzki,et al.  Clinical application of rapid serial fourier-domain optical coherence tomography for macular imaging. , 2006, Ophthalmology.

[13]  M. Naash,et al.  The relationship between opsin overexpression and photoreceptor degeneration. , 2001, Investigative ophthalmology & visual science.

[14]  W. Feuer,et al.  Spectral domain optical coherence tomography in a murine retinal detachment model. , 2009, Experimental eye research.

[15]  Mineo Kondo,et al.  Nrl is required for rod photoreceptor development , 2001, Nature Genetics.

[16]  C. Grimm,et al.  New views on RPE65 deficiency: the rod system is the source of vision in a mouse model of Leber congenital amaurosis , 2001, Nature Genetics.

[17]  D. Chen,et al.  Vascular damage in a mouse model of diabetic retinopathy: relation to neuronal and glial changes. , 2005, Investigative ophthalmology & visual science.

[18]  T. Kern,et al.  Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes , 2007, Diabetologia.

[19]  E. Strettoi,et al.  Inner retinal abnormalities in a mouse model of Leber's congenital amaurosis , 2004, The Journal of comparative neurology.

[20]  A. Hackam,et al.  In vivo three-dimensional high-resolution imaging of rodent retina with spectral-domain optical coherence tomography. , 2007, Investigative ophthalmology & visual science.

[21]  Naoyuki Maeda,et al.  Effects of age, sex, and axial length on the three-dimensional profile of normal macular layer structures. , 2011, Investigative ophthalmology & visual science.

[22]  W. Hauswirth,et al.  Retinal degeneration 12 (rd12): a new, spontaneously arising mouse model for human Leber congenital amaurosis (LCA). , 2005, Molecular vision.

[23]  C. Cepko,et al.  Synaptogenesis and outer segment formation are perturbed in the neural retina of Crx mutant mice , 2005, BMC Neuroscience.

[24]  K. Takahashi,et al.  Optical coherence tomography (OCT) findings in normal retina and laser-induced choroidal neovascularization in rats , 2001, Graefe's Archive for Clinical and Experimental Ophthalmology.

[25]  Vikram S Brar,et al.  Normative data for macular thickness by high-definition spectral-domain optical coherence tomography (spectralis). , 2009, American journal of ophthalmology.

[26]  T. Kern,et al.  A mouse model of diabetic retinopathy. , 1996, Archives of ophthalmology.

[27]  M. Seeliger,et al.  Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[28]  W. Baehr,et al.  Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene of the rd mouse. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Hiroshi Ishikawa,et al.  Reproducibility of spectral-domain optical coherence tomography total retinal thickness measurements in mice. , 2010, Investigative ophthalmology & visual science.

[30]  Hemant Khanna,et al.  Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors. , 2004, Human molecular genetics.

[31]  E. Scott,et al.  Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization , 2002, Nature Medicine.