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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 4, Iss. 8 — Aug. 1, 2013
  • pp: 1285–1293

In vivo two-photon imaging of the mouse retina

Robin Sharma, Lu Yin, Ying Geng, William H. Merigan, Grazyna Palczewska, Krzysztof Palczewski, David R. Williams, and Jennifer J. Hunter  »View Author Affiliations


Biomedical Optics Express, Vol. 4, Issue 8, pp. 1285-1293 (2013)
http://dx.doi.org/10.1364/BOE.4.001285


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Abstract

Though in vivo two-photon imaging has been demonstrated in non-human primates, improvements in the signal-to-noise ratio (SNR) would greatly improve its scientific utility. In this study, extrinsic fluorophores, expressed in otherwise transparent retinal ganglion cells, were imaged in the living mouse eye using a two-photon fluorescence adaptive optics scanning laser ophthalmoscope. We recorded two orders of magnitude greater signal levels from extrinsically labeled cells relative to previous work done in two-photon autofluorescence imaging of primates. Features as small as single dendrites in various layers of the retina could be resolved and predictions are made about the feasibility of measuring functional response from cells. In the future, two-photon imaging in the intact eye may allow us to monitor the function of retinal cell classes with infrared light that minimally excites the visual response.

© 2013 OSA

OCIS Codes
(170.0110) Medical optics and biotechnology : Imaging systems
(330.4460) Vision, color, and visual optics : Ophthalmic optics and devices
(180.4315) Microscopy : Nonlinear microscopy

ToC Category:
Ophthalmology Applications

History
Original Manuscript: March 4, 2013
Revised Manuscript: May 6, 2013
Manuscript Accepted: June 17, 2013
Published: July 9, 2013

Virtual Issues
August 13, 2013 Spotlight on Optics

Citation
Robin Sharma, Lu Yin, Ying Geng, William H. Merigan, Grazyna Palczewska, Krzysztof Palczewski, David R. Williams, and Jennifer J. Hunter, "In vivo two-photon imaging of the mouse retina," Biomed. Opt. Express 4, 1285-1293 (2013)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-4-8-1285


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References

  1. J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A14(11), 2884–2892 (1997). [CrossRef] [PubMed]
  2. A. Roorda, F. Romero-Borja, W. Donnelly Iii, H. Queener, T. Hebert, and M. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express10(9), 405–412 (2002). [CrossRef] [PubMed]
  3. D. C. Gray, W. Merigan, J. I. Wolfing, B. P. Gee, J. Porter, A. Dubra, T. H. Twietmeyer, K. Ahamd, R. Tumbar, F. Reinholz, and D. R. Williams, “In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells,” Opt. Express14(16), 7144–7158 (2006). [CrossRef] [PubMed]
  4. Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express3(4), 715–734 (2012). [CrossRef] [PubMed]
  5. J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci.50(3), 1350–1359 (2008). [CrossRef] [PubMed]
  6. A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(7), 1864–1876 (2011). [CrossRef] [PubMed]
  7. D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol.9(1), 1–9 (2009). [CrossRef] [PubMed]
  8. E. A. Rossi, M. Chung, A. Dubra, J. J. Hunter, W. H. Merigan, and D. R. Williams, “Imaging retinal mosaics in the living eye,” Eye (Lond.)25(3), 301–308 (2011). [CrossRef] [PubMed]
  9. Y. Imanishi, M. L. Batten, D. W. Piston, W. Baehr, and K. Palczewski, “Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye,” J. Cell Biol.164(3), 373–383 (2004). [CrossRef] [PubMed]
  10. Y. Imanishi, K. H. Lodowski, and Y. Koutalos, “Two-photon microscopy: shedding light on the chemistry of vision,” Biochemistry46(34), 9674–9684 (2007). [CrossRef] [PubMed]
  11. J. J. Hunter, B. Masella, A. Dubra, R. Sharma, L. Yin, W. H. Merigan, G. Palczewska, K. Palczewski, and D. R. Williams, “Images of photoreceptors in living primate eyes using adaptive optics two-photon ophthalmoscopy,” Biomed. Opt. Express2(1), 139–148 (2010). [CrossRef] [PubMed]
  12. T. Euler, P. B. Detwiler, and W. Denk, “Directionally selective calcium signals in dendrites of starburst amacrine cells,” Nature418(6900), 845–852 (2002). [CrossRef] [PubMed]
  13. L. Tian, S. A. Hires, T. Mao, D. Huber, M. E. Chiappe, S. H. Chalasani, L. Petreanu, J. Akerboom, S. A. McKinney, E. R. Schreiter, C. I. Bargmann, V. Jayaraman, K. Svoboda, and L. L. Looger, “Imaging neural activity in worms, flies, and mice with improved GCaMP calcium indicators,” Nat. Methods6(12), 875–881 (2009). [CrossRef] [PubMed]
  14. K. Ohki, S. Chung, Y. H. Ch’ng, P. Kara, and R. C. Reid, “Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex,” Nature433(7026), 597–603 (2005). [CrossRef] [PubMed]
  15. L. Yin, Y. Geng, F. Osakada, R. Sharma, A. H. Cetin, E. M. Callaway, D. R. Williams, and W. H. Merigan, “Imaging light responses of retinal ganglion cells in the living mouse eye,” J. Neurophysiol.109(9), 2415–2421 (2013). [CrossRef] [PubMed]
  16. A. Dubra and Z. Harvey, “Registration of 2D Images from Fast Scanning Ophthalmic Instruments,” in Biomedical Image Registration, Lecture Notes in Computer Science, B. Fischer, B. Dawant, and C. Lorenz, eds. (Springer Berlin / Heidelberg, 2010), 6204, 60–71.
  17. J. T. Dobbins III, “Image quality metrics for digital system,” in Handbook of Medical Imaging, Volume 1. Physics and Psychophysics, R. L. Van Metter, J. Beutel, and H. L. Kundel, eds. (SPIE, 2000).
  18. L. Yin, K. Greenberg, J. J. Hunter, D. Dalkara, K. D. Kolstad, B. D. Masella, R. Wolfe, M. Visel, D. Stone, R. T. Libby, D. Diloreto, D. Schaffer, J. Flannery, D. R. Williams, and W. H. Merigan, “Intravitreal injection of AAV2 transduces macaque inner retina,” Invest. Ophthalmol. Vis. Sci.52(5), 2775–2783 (2011). [CrossRef] [PubMed]
  19. F. Osakada, T. Mori, A. H. Cetin, J. H. Marshel, B. Virgen, and E. M. Callaway, “New rabies virus variants for monitoring and manipulating activity and gene expression in defined neural circuits,” Neuron71(4), 617–631 (2011). [CrossRef] [PubMed]
  20. W. Wei, J. Elstrott, and M. B. Feller, “Two-photon targeted recording of GFP-expressing neurons for light responses and live-cell imaging in the mouse retina,” Nat. Protoc.5(7), 1347–1352 (2010). [CrossRef] [PubMed]
  21. M. Pottek, G. C. Knop, R. Weiler, and K. Dedek, “Electrophysiological characterization of GFP-expressing cell populations in the intact retina,” J. Vis. Exp. (57), 13473–13474 (2011). [CrossRef] [PubMed]
  22. B. G. Borghuis, L. Tian, Y. Xu, S. S. Nikonov, N. Vardi, B. V. Zemelman, and L. L. Looger, “Imaging light responses of targeted neuron populations in the rodent retina,” J. Neurosci.31(8), 2855–2867 (2011). [CrossRef] [PubMed]
  23. J. Coombs, D. van der List, G.-Y. Wang, and L. M. Chalupa, “Morphological properties of mouse retinal ganglion cells,” Neuroscience140(1), 123–136 (2006). [CrossRef] [PubMed]
  24. F. Naarendorp, T. M. Esdaille, S. M. Banden, J. Andrews-Labenski, O. P. Gross, and E. N. Pugh., “Dark light, rod saturation, and the absolute and incremental sensitivity of mouse cone vision,” J. Neurosci.30(37), 12495–12507 (2010). [CrossRef] [PubMed]
  25. Y. V. Wang, M. Weick, and J. B. Demb, “Spectral and temporal sensitivity of cone-mediated responses in mouse retinal ganglion cells,” J. Neurosci.31(21), 7670–7681 (2011). [CrossRef] [PubMed]
  26. T. D. Lamb, “Photoreceptor spectral sensitivities: common shape in the long-wavelength region,” Vision Res.35(22), 3083–3091 (1995). [CrossRef] [PubMed]
  27. E. J. Gualda, J. M. Bueno, and P. Artal, “Wavefront optimized nonlinear microscopy of ex vivo human retinas,” J. Biomed. Opt.15(2), 026007 (2010). [CrossRef] [PubMed]
  28. R.-W. Lu, Y.-C. Li, T. Ye, C. Strang, K. Keyser, C. A. Curcio, and X.-C. Yao, “Two-photon excited autofluorescence imaging of freshly isolated frog retinas,” Biomed. Opt. Express2(6), 1494–1503 (2011). [CrossRef] [PubMed]

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