Potenzial von fMRT für die Funktionsüberprüfung des pathologischen Sehsystems

Zusammenfassung

Aktuelle Entwicklungen zur funktionellen Magnetresonanztomografie (fMRT) des menschlichen visuellen Kortex haben eine Reihe von aussagekräftigen Ansätzen hervorgebracht, die vielversprechend für die moderne Ophthalmologie sind. Sie ermöglichen die objektive gesichtsfeldspezifische Überprüfung der Sehfunktion auch bei stark sehbehinderten Patienten und sogar die Untersuchung der funktionellen Organisation des visuellen Kortex von blinden Patienten. Damit eröffnen sie einerseits ein breites Anwendungsspektrum bei der ophthalmologischen Funktionsüberprüfung und andererseits grundlegende Einblicke in die Interaktion von Pathologie und Plastizität im menschlichen Sehsystem. Dies verdeutlichen aktuelle Studien an Patienten mit erworbenen und angeborenen Makuladefekten, Sehbahnabnormalitäten, flächigen Netzhautschäden und vollständiger Blindheit. Insbesondere zukünftige Therapieverfahren zur Restauration des visuellen Eingangs könnten hiervon wesentlich profitieren, sei es bei der Beurteilung der Erfolgschancen einer anstehenden retinalen Therapie oder als Biomarker für das objektive Auslesen des Therapieerfolgs.

Abstract

Current developments in functional magnetic resonance imaging (fMRI) of the human visual system have generated a set of powerful approaches that are of great promise for modern ophthalmology. These make it possible to perform an objective spatially resolved test of visual function in patients with strong visual impairment and even to investigate the functional organisation of the visual cortex in the blind. As a consequence, they open a broad field of applications for functional assessment in ophthalmology and provide fundamental insights into the interplay of pathology and plasticity in the human visual system. This is highlighted by current studies investigating patients with acquired or congenital defects of the macula, or with visual pathway abnormalities, extended retinal damage, and complete blindness. Therapeutic approaches targeting the restoration of visual input are expected to benefit from these fMRI applications, either for the estimation of the success rate of a planned retinal therapy or as an objective high-level biomarker for the readout of therapy success.

Schlüsselwörter

Genetik - Neuroophthalmologie - Retina

Key words

genetics - neuroophthalmology - retina

• Literatur

• 1 Hoffmann MB, Kaule F, Grzeschik R. et al. [Retinotopic mapping of the human visual cortex with functional magnetic resonance imaging – basic principles, current developments and ophthalmological perspectives]. Klin Monatsbl Augenheilkd 2011; 228: 613-620
• 2 Stingl K, Bartz-Schmidt KU, Besch D. et al. Subretinal Visual Implant Alpha IMS—Clinical trial interim report. Vision Res 2015; 111: 149-160
• 3 Zobor D, Zobor G, Kohl S. Achromatopsia: on the doorstep of a possible therapy. Ophthalmic Res 2015; 54: 103-108
• 4 Wandell BA, Winawer J. Computational neuroimaging and population receptive fields. Trends Cogn Sci 2015; 19: 349-357
• 5 Horton JC, Hoyt WF. The representation of the visual field in human striate cortex. A revision of the classic Holmes map. Arch Ophthal 1991; 109: 816-824
• 6 Wandell BA, Dumoulin SO, Brewer AA. Visual field maps in human cortex. Neuron 2007; 56: 366-383
• 7 Logothetis NK, Pauls J, Augath M. et al. Neurophysiological investigation of the basis of the fMRI signal. Nature 2001; 412: 150-157
• 8 Engel SA, Rumelhart DE, Wandell BA. et al. fMRI of human visual cortex. Nature 1994; 369: 525
• 9 Engel SA, Glover GH, Wandell BA. Retinotopic organization in human visual cortex and the spatial precision of functional MRI. Cereb Cortex 1997; 7: 181-192
• 10 Sereno MI, Dale AM, Reppas JB. et al. Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging. [see comment]. Science 1995; 268: 889-893 comment in: Science 1995; 268: 803–804
• 11 DeYoe EA, Carman GJ, Bandettini P. et al. Mapping striate and extrastriate visual areas in human cerebral cortex. Proc Natl Acad Sci U S A 1996; 93: 2382-2386
• 12 Dumoulin SO, Wandell BA. Population receptive field estimates in human visual cortex. Neuroimage 2008; 39: 647-660
• 13 Ackroyd C, Humphrey NK, Warrington EK. Lasting effects of early blindness. A case study. Q J Exp Psychol 1974; 26: 114-124
• 14 Carlson S, Hyvarinen L, Raninen A. Persistent behavioural blindness after early visual deprivation and active visual rehabilitation: a case report. Br J Ophthalmol 1986; 70: 607-611
• 15 Ostrovsky Y, Andalman A, Sinha P. Vision following extended congenital blindness. Psychol Sci 2006; 17: 1009-1014
• 16 Fine I, Wade AR, Brewer AA. et al. Long-term deprivation affects visual perception and cortex. Nat Neurosci 2003; 6: 915-916
• 17 Levin N, Dumoulin SO, Winawer J. et al. Cortical maps and white matter tracts following long period of visual deprivation and retinal image restoration. Neuron 2010; 65: 21-31
• 18 Baker CI, Dilks DD, Peli E. et al. Reorganization of visual processing in macular degeneration: replication and clues about the role of foveal loss. Vision Res 2008; 48: 1910-1919
• 19 Schumacher EH, Jacko JA, Primo SA. et al. Reorganization of visual processing is related to eccentric viewing in patients with macular degeneration. Restor Neurol Neurosci 2008; 26: 391-402
• 20 Dilks DD, Baker CI, Peli E. et al. Reorganization of visual processing in macular degeneration is not specific to the “preferred retinal locus”. J Neurosci 2009; 29: 2768-2773
• 21 Masuda Y, Dumoulin SO, Nakadomari S. et al. V1 projection zone signals in human macular degeneration depend on task, not stimulus. Cereb Cortex 2008; 18: 2483-2493
• 22 Sunness JS, Liu T, Yantis S. Retinotopic mapping of the visual cortex using functional magnetic resonance imaging in a patient with central scotomas from atrophic macular degeneration. Ophthalmology 2004; 111: 1595-1598
• 23 Baseler HA, Gouws A, Morland AB. The organization of the visual cortex in patients with scotomata resulting from lesions of the central retina. Neuroophthalmology 2009; 33: 149-157
• 24 Wandell BA, Smirnakis SM. Plasticity and stability of visual field maps in adult primary visual cortex. Nat Rev Neurosci 2009; 10: 873-884
• 25 Baseler HA, Gouws A, Haak KV. et al. Large-scale remapping of visual cortex is absent in adult humans with macular degeneration. Nat Neurosci 2011; 14: 649-655
• 26 Barton B, Brewer AA. fMRI of the rod scotoma elucidates cortical rod pathways and implications for lesion measurements. Proc Natl Acad Sci U S A 2015; 112: 5201-5206
• 27 Baseler HA, Brewer AA, Sharpe LT. et al. Reorganization of human cortical maps caused by inherited photoreceptor abnormalities. Nat Neurosci 2002; 5: 364-370
• 28 Michalakis S, Mühlfriedel R, Tanimoto N. et al. Restoration of cone vision in the CNGA3-/- mouse model of congenital complete lack of cone photoreceptor function. Mol Ther 2010; 18: 2057-2063
• 29 Montoliu L, Gronskov K, Wei AH. et al. Increasing the complexity: new genes and new types of albinism. Pigment Cell Melanoma Res 2013; 27: 11-18
• 30 Hoffmann MB, Lorenz B, Morland AB. et al. Misrouting of the optic nerves in albinism: estimation of the extent with visual evoked potentials. Invest Ophthalmol Vis Sci 2005; 46: 3892-3898
• 31 Hoffmann MB, Tolhurst DJ, Moore AT. et al. Organization of the visual cortex in human albinism. J Neurosci 2003; 23: 8921-8930
• 32 Hoffmann MB, Dumoulin SO. Congenital visual pathway abnormalities: a window onto cortical stability and plasticity. Trends Neurosci 2015; 38: 55-65
• 33 Hoffmann MB, Kaule FR, Levin N. et al. Plasticity and stability of the visual system in human achiasma. Neuron 2012; 75: 393-401
• 34 Kaule FR, Wolynski B, Gottlob I. et al. Impact of chiasma opticum malformations on the organization of the human ventral visual cortex. Hum Brain Mapp 2014; 35: 5093-5105
• 35 Wolynski B, Kanowski M, Meltendorf S. et al. Self-organisation in the human visual system—visuo-motor processing with congenitally abnormal V1 input. Neuropsychologia 2010; 48: 3834-3845
• 36 Guillery RW. Anatomical pathways that link perception and action. Prog Brain Res 2005; 149: 235-256
• 37 Klemen J, Hoffmann MB, Chambers CD. Cortical plasticity in the face of congenitally altered input into V1. Cortex 2012; 48: 1362-1365
• 38 Hoffmann MB, Seufert PS, Schmidtborn LC. Perceptual relevance of abnormal visual field representations – static visual field perimetry in human albinism. Br J Ophthalmol 2007; 91: 509-513
• 39 Sengupta A, Kaule FR, Guntupalli JS. et al. A studyforrest extension, retinotopic mapping and localization of higher visual areas. Sci Data 2016; 3: 160093
• 40 Benson NC, Butt OH, Datta R. et al. The retinotopic organization of striate cortex is well predicted by surface topology. Curr Biol 2012; 22: 2081-2085
• 41 Benson NC, Butt OH, Brainard DH. et al. Correction of distortion in flattened representations of the cortical surface allows prediction of V1-V3 functional organization from anatomy. PLoS Comput Biol 2014; 10: e1003538
• 42 Bainbridge JW, Smith AJ, Barker SS. et al. Effect of gene therapy on visual function in Leberʼs congenital amaurosis. N Engl J Med 2008; 358: 2231-2239
• 43 Maguire AM, Simonelli F, Pierce EA. et al. Safety and efficacy of gene transfer for Leberʼs congenital amaurosis. N Engl J Med 2008; 358: 2240-2248
• 44 Hauswirth WW, Aleman TS, Kaushal S. et al. Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther 2008; 19: 979-990
• 45 Cideciyan AV, Aleman TS, Boye SL. et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci U S A 2008; 105: 15112-15117
• 46 Ashtari M, Cyckowski LL, Monroe JF. et al. The human visual cortex responds to gene therapy-mediated recovery of retinal function. J Clin Invest 2011; 121: 2160-2168
• 47 Bennett J, Ashtari M, Wellman J. et al. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med 2012; 4: 120ra115
• 48 Koenekoop RK, Sui R, Sallum J. et al. Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial. Lancet 2014; 384: 1513-1520
• 49 Cideciyan AV, Aguirre GK, Jacobson SG. et al. Pseudo-fovea formation after gene therapy for RPE65-LCA. Invest Ophthalmol Vis Sci 2015; 56: 526-537
• 50 Hanke M, Baumgartner FJ, Ibe P. et al. A high-resolution 7-Tesla fMRI dataset from complex natural stimulation with an audio movie. Sci Data 2014; 1: 140003
• 51 Arcaro MJ, Honey CJ, Mruczek RE. et al. Widespread correlation patterns of fMRI signal across visual cortex reflect eccentricity organization. Elife 2015;
• 52 Gravel N, Harvey B, Nordhjem B. et al. Cortical connective field estimates from resting state fMRI activity. Front Neurosci 2014; 8: 339
• 53 Haak KV, Winawer J, Harvey BM. et al. Connective field modeling. Neuroimage 2013; 66: 376-384
• 54 Striem-Amit E, Ovadia-Caro S, Caramazza A. et al. Functional connectivity of visual cortex in the blind follows retinotopic organization principles. Brain 2015; 138: 1679-1695
• 55 Bock AS, Binda P, Benson NC. et al. Resting-State Retinotopic Organization in the Absence of Retinal Input and Visual Experience. J Neurosci 2015; 35: 12366-12382
• 56 Hernowo AT, Prins D, Baseler HA. et al. Morphometric analyses of the visual pathways in macular degeneration. Cortex 2014; 56: 99-110
• 57 Boucard CC, Hanekamp S, Curcic-Blake B. et al. Neurodegeneration beyond the primary visual pathways in a population with a high incidence of normal-pressure glaucoma. Ophthalmic Physiol Opt 2016; 36: 344-353
• 58 Hernowo AT, Boucard CC, Jansonius NM. et al. Automated morphometry of the visual pathway in primary open-angle glaucoma. Invest Ophthalmol Vis Sci 2011; 52: 2758-2766
• 59 Prins D, Hanekamp S, Cornelissen FW. Structural brain MRI studies in eye diseases: are they clinically relevant? A review of current findings. Acta Ophthalmol 2016; 94: 113-121