White matter consequences of retinal receptor and ganglion cell damage.

PURPOSE Patients with Leber hereditary optic neuropathy (LHON) and cone-rod dystrophy (CRD) have central vision loss; but CRD damages the retinal photoreceptor layer, and LHON damages the retinal ganglion cell (RGC) layer. Using diffusion MRI, we measured how these two types of retinal damage affect the optic tract (ganglion cell axons) and optic radiation (geniculo-striate axons). METHODS Adult onset CRD (n = 5), LHON (n = 6), and healthy controls (n = 14) participated in the study. We used probabilistic fiber tractography to identify the optic tract and the optic radiation. We compared axial and radial diffusivity at many positions along the optic tract and the optic radiation. RESULTS In both types of patients, diffusion measures within the optic tract and the optic radiation differ from controls. The optic tract change is principally a decrease in axial diffusivity; the optic radiation change is principally an increase in radial diffusivity. CONCLUSIONS Both photoreceptor layer (CRD) and retinal ganglion cell (LHON) retinal disease causes substantial change in the visual white matter. These changes can be measured using diffusion MRI. The diffusion changes measured in the optic tract and the optic radiation differ, suggesting that they are caused by different biological mechanisms.

[1]  M. Claustres,et al.  [Molecular genetics of pigmentary retinopathies: identification of mutations in CHM, RDS, RHO, RPE65, USH2A and XLRS1 genes]. , 2000, Journal francais d'ophtalmologie.

[2]  Brian A. Wandell,et al.  Plasticity and Stability of the Visual System in Human Achiasma , 2012, Neuron.

[3]  P. V. van Zijl,et al.  Analysis of noise effects on DTI‐based tractography using the brute‐force and multi‐ROI approach , 2004, Magnetic resonance in medicine.

[4]  G. Fishman,et al.  Peripapillary retinal nerve fiber layer thinning in patients with autosomal recessive cone-rod dystrophy. , 2009, American journal of ophthalmology.

[5]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[6]  P. Win,et al.  Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve. , 2000, Transactions of the American Ophthalmological Society.

[7]  S. Jacobson,et al.  Cone-Rod Dystrophy: Phenotypic Diversity by Retinal Function Testing , 1989 .

[8]  V. Wedeen,et al.  Fiber crossing in human brain depicted with diffusion tensor MR imaging. , 2000, Radiology.

[9]  P. Chinnery,et al.  Gene–environment interactions in Leber hereditary optic neuropathy , 2009, Brain : a journal of neurology.

[10]  Karl J. Friston,et al.  Generative and recognition models for neuroanatomy , 2004, NeuroImage.

[11]  F. Garaci,et al.  3-T Diffusion tensor imaging of the optic nerve in subjects with glaucoma: correlation with GDx-VCC, HRT-III and Stratus optical coherence tomography findings , 2012, British Journal of Ophthalmology.

[12]  Anthony J. Sherbondy,et al.  Identifying the human optic radiation using diffusion imaging and fiber tractography. , 2008, Journal of vision.

[13]  P. Sieving,et al.  Mutations in the Cone-Rod Homeobox Gene Are Associated with the Cone-Rod Dystrophy Photoreceptor Degeneration , 1997, Neuron.

[14]  G. Savini,et al.  Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy. , 2005, Ophthalmology.

[15]  D. Purves,et al.  Correlated Size Variations in Human Visual Cortex, Lateral Geniculate Nucleus, and Optic Tract , 1997, The Journal of Neuroscience.

[16]  N. Yoshimura,et al.  Longitudinal analysis of the peripapillary retinal nerve fiber layer thinning in patients with retinitis pigmentosa , 2013, Eye.

[17]  Sabine Kastner,et al.  Functional imaging of the human lateral geniculate nucleus and pulvinar. , 2004, Journal of neurophysiology.

[18]  S. Nelson,et al.  Topographic organization of the optic radiation of the cat , 1985, The Journal of comparative neurology.

[19]  Jian Wang,et al.  Reduced white matter integrity in primary open-angle glaucoma: a DTI study using tract-based spatial statistics. , 2013, Journal of neuroradiology. Journal de neuroradiologie.

[20]  Eliza M. Gordon-Lipkin,et al.  Damage to the optic radiation in multiple sclerosis is associated with retinal injury and visual disability. , 2009, Archives of neurology.

[21]  B. Wandell,et al.  Tract Profiles of White Matter Properties: Automating Fiber-Tract Quantification , 2012, PloS one.

[22]  G. Plant,et al.  Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography. , 2009, Brain : a journal of neurology.

[23]  J. L. Stone,et al.  Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. , 1992, Archives of ophthalmology.

[24]  W F Hoyt,et al.  Magnetic resonance imaging of the human lateral geniculate body. , 1990, Archives of neurology.

[25]  D. Turnbull,et al.  The epidemiology of Leber hereditary optic neuropathy in the North East of England. , 2003, American journal of human genetics.

[26]  G. Savini,et al.  Retinal nerve fiber layer evaluation by optical coherence tomography in unaffected carriers with Leber's hereditary optic neuropathy mutations. , 2005, Ophthalmology.

[27]  P. Hüppi,et al.  Diffusion tensor imaging of normal and injured developing human brain ‐ a technical review , 2002, NMR in biomedicine.

[28]  B. Wandell,et al.  Cortical Maps and White Matter Tracts following Long Period of Visual Deprivation and Retinal Image Restoration , 2010, Neuron.

[29]  D. Yin,et al.  Whole-brain voxel-based analysis of diffusion tensor MRI parameters in patients with primary open angle glaucoma and correlation with clinical glaucoma stage , 2013, Neuroradiology.

[30]  Xuelin Zhang,et al.  Diffusion tensor imaging reveals normal geniculocalcarine-tract integrity in acquired blindness , 2012, Brain Research.

[31]  J. VanBuren.  TRANS-SYNAPTIC RETROGRADE DEGENERATION IN THE VISUAL SYSTEM OF PRIMATES. , 1963, Journal of neurology, neurosurgery, and psychiatry.

[32]  S. Rossi,et al.  Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research , 2009, Clinical Neurophysiology.

[33]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[34]  N. Yoshimura,et al.  Retinal nerve fiber layer thickness in patients with retinitis pigmentosa , 2009, Eye.

[35]  Jens Frahm,et al.  Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity , 2012, Nature.

[36]  P. Chinnery,et al.  Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies , 2011, Progress in Retinal and Eye Research.

[37]  Alice K. Cho,et al.  Retinal prostheses: current clinical results and future needs. , 2011, Ophthalmology.

[38]  V. Carelli,et al.  Mathematically modeling the involvement of axons in Leber's hereditary optic neuropathy. , 2012, Investigative ophthalmology & visual science.

[39]  Andrew S. Bock,et al.  Visual callosal topography in the absence of retinal input , 2013, NeuroImage.

[40]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[41]  M. Filippi,et al.  Evidence for retrochiasmatic tissue loss in Leber's hereditary optic neuropathy , 2010, Human brain mapping.

[42]  Joachim Hornegger,et al.  Glaucoma classification based on visual pathway analysis using diffusion tensor imaging. , 2013, Magnetic resonance imaging.

[43]  K. Sung,et al.  Comparison of retinal nerve fiber layer thickness measured by Cirrus HD and Stratus optical coherence tomography. , 2009, Ophthalmology.

[44]  N. Gupta,et al.  Atrophy of the lateral geniculate nucleus in human glaucoma detected by magnetic resonance imaging , 2008, British Journal of Ophthalmology.

[45]  P. Basser,et al.  Diffusion tensor MR imaging of the human brain. , 1996, Radiology.

[46]  S. Liebowitz.  Retinitis pigmentosa. , 1979, Journal - American Intra-Ocular Implant Society.

[47]  M. Kiyosawa,et al.  Positive correlation between the degree of visual field defect and optic radiation damage in glaucoma patients , 2013, Japanese Journal of Ophthalmology.

[48]  S. Schwartz,et al.  Embryonic stem cell trials for macular degeneration: a preliminary report , 2012, The Lancet.

[49]  T. Struffert,et al.  A new approach to assess intracranial white matter abnormalities in glaucoma patients: changes of fractional anisotropy detected by 3T diffusion tensor imaging. , 2012, Academic Radiology.

[50]  D. Manners,et al.  Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy , 2012, PloS one.

[51]  M. Filippi,et al.  Patterns of white matter diffusivity abnormalities in Leber’s hereditary optic neuropathy: a tract-based spatial statistics study , 2012, Journal of Neurology.

[52]  N. Gupta,et al.  Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex , 2006, British Journal of Ophthalmology.

[53]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[54]  J. Vonsattel,et al.  Direct demonstration of transsynaptic degeneration in the human visual system: a comparison of retrograde and anterograde changes , 1982, Journal of neurology, neurosurgery, and psychiatry.

[55]  Geoff J M Parker,et al.  Optic radiation changes after optic neuritis detected by tractography‐based group mapping , 2005, Human brain mapping.

[56]  Christine C. Boucard,et al.  Automated morphometry of the visual pathway in primary open-angle glaucoma. , 2011, Investigative ophthalmology & visual science.

[57]  R. Sergott.  Natural History of Leber's Hereditary Optic Neuropathy: Longitudinal Analysis of the Retinal Nerve Fiber Layer by Optical Coherence Tomography , 2010 .

[58]  A. Flanders.  Optic Nerve and Optic Radiation Neurodegeneration in Patients with Glaucoma: In Vivo Analysis with 3-T Diffusion-Tensor MR Imaging , 2010 .

[59]  A. Sher,et al.  Photovoltaic Retinal Prosthesis with High Pixel Density , 2012, Nature Photonics.

[60]  Anthony J. Sherbondy,et al.  ConTrack: finding the most likely pathways between brain regions using diffusion tractography. , 2008, Journal of vision.

[61]  Giacinto Bagetta,et al.  Brain involvement in glaucoma: advanced neuroimaging for understanding and monitoring a new target for therapy. , 2013, Current opinion in pharmacology.

[62]  N. Newman,et al.  The neuro-ophthalmology of mitochondrial disease. , 2010, Survey of ophthalmology.

[63]  U. Ebeling,et al.  Neurosurgical topography of the optic radiation in the temporal lobe , 2005, Acta Neurochirurgica.

[64]  J. M. Buren.  Trans-synaptic retrograde degeneration in the visual system of primates , 1963, Journal of neurology, neurosurgery, and psychiatry.

[65]  U. Bürgel,et al.  Diffusion tensor imaging in acquired blind humans , 2006, Neuroscience Letters.

[66]  Michael Erb,et al.  NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels , 2011, PloS one.

[67]  B. Wandell,et al.  Functional organization of human occipital-callosal fiber tracts. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[68]  A. Milam,et al.  Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa. , 1999, Investigative ophthalmology & visual science.

[69]  F. Goldby.  A NOTE ON TRANSNEURONAL ATROPHY IN THE HUMAN LATERAL GENICULATE BODY , 1957, Journal of neurology, neurosurgery, and psychiatry.

[70]  R. A. Pearson,et al.  Advances in repairing the degenerate retina by rod photoreceptor transplantation☆ , 2014, Biotechnology advances.

[71]  John Russell,et al.  Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water , 2002, NeuroImage.

[72]  T. M. Phan,et al.  Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy. , 2012, Ophthalmology.

[73]  T. Hirai,et al.  MR changes in the calcarine area resulting from retinal degeneration. , 1997, AJNR. American journal of neuroradiology.

[74]  Stephen W Scherer,et al.  Cone-Rod Dystrophy Due to Mutations in a Novel Photoreceptor-Specific Homeobox Gene ( CRX ) Essential for Maintenance of the Photoreceptor , 1997, Cell.

[75]  P. Basser,et al.  Comprehensive approach for correction of motion and distortion in diffusion‐weighted MRI , 2004, Magnetic resonance in medicine.

[76]  Jessica I. Wolfing,et al.  High-resolution retinal imaging of cone-rod dystrophy. , 2006, Ophthalmology.