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Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics

| EXPLORING THE INTERFACE OF LIGHT AND BIOMEDICINE

  • Editor: Gregory W. Faris
  • Vol. 5, Iss. 7 — Apr. 26, 2010
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High spatiotemporal resolution imaging of fast intrinsic optical signals activated by retinal flicker stimulation

Yang-Guo Li, Qiu-Xiang Zhang, Lei Liu, Franklin R. Amthor, and Xin-Cheng Yao  »View Author Affiliations


Optics Express, Vol. 18, Issue 7, pp. 7210-7218 (2010)
http://dx.doi.org/10.1364/OE.18.007210


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Abstract

High resolution monitoring of stimulus-evoked retinal neural activities is important for understanding retinal neural mechanisms, and can be a powerful tool for retinal disease diagnosis and treatment outcome evaluation. Fast intrinsic optical signals (IOSs), which have the time courses comparable to that of electrophysiological activities in the retina, hold the promise for high resolution imaging of retinal neural activities. However, application of fast IOS imaging has been hindered by the contamination of slow, high magnitude optical responses associated with transient hemodynamic and metabolic changes. In this paper we demonstrate the feasibility of separating fast retinal IOSs from slow optical responses by combining flicker stimulation and dynamic (temporal) differential image processing. A near infrared flood-illumination microscope equipped with a high-speed (1000 Hz) digital camera was used to conduct concurrent optical imaging and ERG measurement of isolated frog retinas. High spatiotemporal resolution imaging revealed that fast IOSs could follow flicker frequency up to at least 6 Hz. Comparable time courses of fast IOSs and ERG kinetics provide evidence that fast IOSs are originated from stimulus activated retinal neurons.

© 2010 OSA

1. Introduction

High resolution imaging of stimulus-evoked retinal neural activities is important for understanding of visual information processing mechanisms in the retina. High resolution evaluation of localized retinal dysfunction can also be used in disease diagnosis and treatment outcome evaluation. It is well established that many eye diseases can cause pathological changes of photoreceptors and/or inner retinal neurons that ultimately lead to vision losses and even complete blindness. Different eye diseases, such as glaucoma [1

1. R. W. Nickells, “Ganglion cell death in glaucoma: from mice to men,” Vet. Ophthalmol. 10(s1Suppl 1), 88–94 (2007). [CrossRef] [PubMed]

, 2

2. R. S. Harwerth and H. A. Quigley, “Visual field defects and retinal ganglion cell losses in patients with glaucoma,” Arch. Ophthalmol. 124(6), 853–859 (2006). [CrossRef] [PubMed]

], diabetic retinopathy [3

3. B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007). [CrossRef]

, 4

4. Y. W. Qin, G. Z. Xu, and W. J. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006). [CrossRef] [PubMed]

], and macular degeneration [5

5. R. E. Hogg and U. Chakravarthy, “Visual function and dysfunction in early and late age-related maculopathy,” Prog. Retin. Eye Res. 25(3), 249–276 (2006). [CrossRef] [PubMed]

], are known to target at different types of retinal neurons, causing localized lesions. Electroretinogram (ERG) [6

6. H. P. Scholl and E. Zrenner, “Electrophysiology in the investigation of acquired retinal disorders,” Surv. Ophthalmol. 45(1), 29–47 (2000). [CrossRef] [PubMed]

] and multifocal ERG [7

7. D. C. Hood, J. G. Odel, C. S. Chen, and B. J. Winn, “The multifocal electroretinogram,” J. Neuroophthalmol. 23(3), 225–235 (2003). [PubMed]

, 8

8. D. C. Hood, “Assessing retinal function with the multifocal technique,” Prog. Retin. Eye Res. 19(5), 607–646 (2000). [CrossRef] [PubMed]

] are frequently used to measure retinal neural activities, but the spatial resolution of ERG may not be high enough to capture the subtle pathological changes in the early stage of these diseases because ERG signals are pooled from an extended retinal area. Given the delicate structures and complicated functional interactions of the retina, detection of localized dysfunction of different cell populations requires a method that can examine stimulus-evoked retinal neural activities at high spatial and temporal resolutions.

It is possible to optically record stimulus-evoked neural activities in 3 dimensions with high spatial (~µm) resolution. A variety of voltage-sensitive dyes and ion selective indicators have been used to facilitate optical imaging of dynamic neural activity [9

9. B. J. Baker, H. Lee, V. A. Pieribone, L. B. Cohen, E. Y. Isacoff, T. Knopfel, and E. K. Kosmidis, “Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells,” J. Neurosci. Methods 161(1), 32–38 (2007). [CrossRef]

, 10

10. M. Djurisic, M. Zochowski, M. Wachowiak, C. X. Falk, L. B. Cohen, and D. Zecevic, “Optical monitoring of neural activity using voltage-sensitive dyes,” Methods Enzymol. 361, 423–451 (2003). [CrossRef] [PubMed]

]. However, potential phototoxicity of the dyes and the difficult loading procedures limit the applications of these techniques, especially in human subjects. Optical imaging of transient changes of intrinsic optical parameters in activated neural tissues avoids exogenous dyes or indicators. Fast intrinsic optical signals (IOSs) that are closely associated with action potentials and postsynaptic potentials have been observed in dissected neural tissue [11

11. L. B. Cohen, R. D. Keynes, and B. Hille, “Light scattering and birefringence changes during nerve activity,” Nature 218(5140), 438–441 (1968). [CrossRef] [PubMed]

, 12

12. I. Tasaki, A. Watanabe, R. Sandlin, and L. Carnay, “Changes in fluorescence, turbidity, and birefringence associated with nerve excitation,” Proc. Natl. Acad. Sci. U.S.A. 61(3), 883–888 (1968). [CrossRef] [PubMed]

]. Transient IOSs tightly correlated with phototransduction procedures have been also detected in isolated outer segments of photoreceptors [13

13. K. P. Hofmann, R. Uhl, W. Hoffmann, and W. Kreutz, “Measurements on fast light-induced light-scattering and -absorption changes in outer segments of vertebrate light sensitive rod cells,” Biophys. Struct. Mech. 2(1), 61–77 (1976). [CrossRef] [PubMed]

15

15. M. Michel-Villaz, A. Brisson, Y. Chapron, and H. Saibil, “Physical analysis of light-scattering changes in bovine photoreceptor membrane suspensions,” Biophys. J. 46(5), 655–662 (1984). [CrossRef] [PubMed]

] and isolated retinas [16

16. H. H. Harary, J. E. Brown, and L. H. Pinto, “Rapid light-induced changes in near infrared transmission of rods in Bufo marinus,” Science 202(4372), 1083–1085 (1978). [CrossRef] [PubMed]

, 17

17. D. R. Pepperberg, M. Kahlert, A. Krause, and K. P. Hofmann, “Photic modulation of a highly sensitive, near-infrared light-scattering signal recorded from intact retinal photoreceptors,” Proc. Proc. Natl. Acad. Sci. 85(15), 5531–5535 (1988). [CrossRef]

]. Both time-domain [18

18. X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005). [CrossRef] [PubMed]

, 19

19. K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, “Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography,” Proc. Natl. Acad. Sci. U.S.A. 103(13), 5066–5071 (2006). [CrossRef] [PubMed]

] and frequency-domain [20

20. V. J. Srinivasan, M. Wojtkowski, J. G. Fujimoto, and J. S. Duker, “In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography,” Opt. Lett. 31(15), 2308–2310 (2006). [CrossRef] [PubMed]

, 21

21. V. J. Srinivasan, Y. Chen, J. S. Duker, and J. G. Fujimoto, “In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT,” Opt. Express 17(5), 3861–3877 (2009). [CrossRef] [PubMed]

] optical coherence tomography (OCT) imagers have been used for depth-resolved recording of IOSs from isolated retinas [18

18. X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005). [CrossRef] [PubMed]

, 19

19. K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, “Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography,” Proc. Natl. Acad. Sci. U.S.A. 103(13), 5066–5071 (2006). [CrossRef] [PubMed]

] and in intact eyes [20

20. V. J. Srinivasan, M. Wojtkowski, J. G. Fujimoto, and J. S. Duker, “In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography,” Opt. Lett. 31(15), 2308–2310 (2006). [CrossRef] [PubMed]

, 21

21. V. J. Srinivasan, Y. Chen, J. S. Duker, and J. G. Fujimoto, “In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT,” Opt. Express 17(5), 3861–3877 (2009). [CrossRef] [PubMed]

]. Recent development of adaptive optics imagers [22

22. K. Grieve and A. Roorda, “Intrinsic signals from human cone photoreceptors,” Invest. Ophthalmol. Vis. Sci. 49(2), 713–719 (2008). [CrossRef] [PubMed]

, 23

23. R. S. Jonnal, J. Rha, Y. Zhang, B. Cense, W. H. Gao, and D. T. Miller, “In vivo functional imaging of human cone photoreceptors,” Opt. Express 15(24), 16141–16160 (2007). [CrossRef] [PubMed]

] has made in vivo IOS imaging of phototransduction changes of individual photoreceptors possible. However, clinical applications of IOSs for retinal diseases diagnosis have been hindered by their low sensitivity and limited specificity.

Transient IOSs recorded in the retina usually consist of stimulus-evoked retinal neural activities and corresponding metabolic changes of neural- and non-neural (such as glial) cells and hemodynamic activities. IOSs associated with hemodynamic and metabolic changes [24

24. D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005). [PubMed]

, 25

25. M. D. Abràmoff, Y. H. Kwon, D. Ts’o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, “Visual stimulus-induced changes in human near-infrared fundus reflectance,” Invest. Ophthalmol. Vis. Sci. 47(2), 715–721 (2006). [CrossRef] [PubMed]

] can be used to infer the physiological well-being of the retina, but they are not direct measure of neural activities. On the other hand, it has been demonstrated that fast IOSs have the time courses that are comparable to that of the retinal electrophysiological kinetics, i.e., electroretinogram (ERG) responses [26

26. J. L. Schei, M. D. McCluskey, A. J. Foust, X. C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008). [CrossRef] [PubMed]

, 27

27. X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008). [CrossRef] [PubMed]

]. Imaging fast IOSs may thus provide a new method to directly evaluate the functional integrity of photoreceptors and inner retina neurons. However, clinical applications of fast IOSs imaging require effective control of the signal contamination from the slow optical responses of hemodynamic and metabolic changes. Electrophysiological studies have demonstrated that only neural cells can track fast temporal changes (e.g., > 2 Hz) in light stimulus, and it is well established that flicker ERG can be used to separate electrophysiological responses of different retinal cells, such as rod- and cone-systems [28

28. N. S. Peachey, K. R. Alexander, D. J. Derlacki, and G. A. Fishman, “Light adaptation, rods, and the human cone flicker ERG,” Vis. Neurosci. 8(2), 145–150 (1992). [CrossRef] [PubMed]

]. We demonstrate in this paper the feasibility of separating fast IOSs from slow optical responses by combining dynamic differential imaging and high frequency flicker stimulation. High-speed (1000 Hz) differential imaging revealed that fast IOSs could follow flicker stimuli up to at least 6 Hz, similar to the simultaneously recorded ERG signals.

2. Methods

2.1. Preparation of isolated retinas

2.2. Experimental setup

A flood-illumination microscope was modified for near infrared (NIR) light imaging of dynamic IOSs in stimulus activated isolated retinas. As shown in Fig. 1
Fig. 1 Schematic diagram of the flood-illumination imager for NIR light imaging of fast IOSs. During the measurement, the isolated frog retina was illuminated continuously by the NIR light for recording of stimulus-evoked IOSs; while the visible light stimulator was used for retinal stimulation. Concurrent ERG measurement was conducted to record electrophysiological responses associated with retinal activation. At the dichroic mirror (DM), visible stimulus light was reflected and NIR recording light was passed through. The NIR filter was used to block visible stimulus light, and allow the NIR probe light to reach the CMOS camera.
, the imaging system consisted of two (i.e., NIR and visible) light sources. The NIR light was used for IOS recording, and the visible light was used for retinal stimulation. The NIR light was produced by a 12-V 100-W halogen lamp (PHILIPS7724) with a band-pass filter (wavelength band: 800-1000 nm) in front, and the visible light stimulator was a fiber-coupled green light emitting diode (LED) with the central wavelength at 505-nm. The overall power of the NIR light delivered at the retina was ~1mW. Visible flicker stimuli between 1 and 6 Hz were used in this study. These were square pulses from a dark background. Each stimulus pulse had a 10-ms duration, with an intensity of ~104 505-nm photons·µm−2·ms−1. Each recording session consisted of a 0.5-s pre-stimulus baseline image recording phase in total darkness, followed by a 3-s flicker stimulus phase, and then followed by a 1.5-s post-stimulus images recording phase, again in total darkness. It was estimated that <1% of the total photopigment was bleached by each stimulus pulse.

The images shown in this paper were recorded using a 10 bit CMOS camera (PCO1200, PCO AG, Kelheim, Germany), running at a frame rate of 1000 frames/s and spatial size of 400 x 400 pixels. The CMOS camera has 2 GB built-in RAM for fast image recording with a transfer speed of 820 MB/s. The ultrafast transfer speed made it possible to collect optical images at a high frame rate while allowing sufficient exposure time to ensure image quality. This imager allowed us to characterize fast IOSs with ms temporal resolution and µm spatial resolution. During the recording session, the frog retina was immersed in Ringer solution and pressed to a multi-electrode array. The photoreceptor layer was upward, closest to the visible light stimulus. The ganglion cell layer was in contact with the multi-electrode array for ERG measurement [18

18. X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005). [CrossRef] [PubMed]

].

2.3. Data processing

IOS images shown in Fig. 2a
Fig. 2 (a) IOS imaging of frog retina activated by 1.0 Hz flicker stimulation. Arrowheads represent the delivery of the flicker pulses. (b) Dynamic differential IOS imaging of the same retina shown in a. Raw images were acquired with a frame speed of 1000 frames/s. Each illustrated frame is an average of 250 frames over 250 ms interval. Each stimulus pulse lasted 10 ms (c) Enlargement of the 7th frame in b. (d) Gray and black traces 1-3 show IOSs and dynamic differential IOSs of retinal areas marked by the red squares 1-3 in c. Green trace depicts the flicker stimuli. (e) Statistics of IOSs in the activated retina shown in a. (f) Statistics of dynamic differential IOSs in the activated retina shown in b. A threshold (0.5% ΔI/I) was used to reduce the effect of background noises on the statistics. In e and f, the red and blue traces present the ratios of retinal areas with positive and negative IOSs, respectively. The black trace shows the difference (i.e. subtraction of the red and blue traces) of the retinal areas with positive and negative IOSs.
are stimulus-evoked optical responses represented in the unit of ΔI/I, where ΔI is the dynamic optical changes and I is the background light intensity. The IOS images were constructed using the following procedure [27

27. X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008). [CrossRef] [PubMed]

]: 1) The images from the 0.5-s pre-stimulus baseline recording phase were averaged, pixel by pixel, and the averaged intensity of each pixel was taken as the background intensity I of each pixel; 2) The background intensity I was subtracted from each subsequent recorded frame, pixel by pixel, to get the ΔI of each pixel. 3) The ΔI/I image sequence was constructed to show the dynamic IOS patterns of the retina.

In order to reduce the contamination of optical signal due to metabolic changes of activated retinal cells, a dynamic differential processing procedure was used to separate fast IOSs from slow optical changes (Fig. 4a
Fig. 4 (a) P1 and T1 present the peak magnitude and time delay (relative to the stimulus onset) of the optical response evoked by the first stimulus flash, and P2 and T2 show averaged peak magnitude and time delay of optical responses elicited by the following stimuli. (b) Comparison of P1 and P2 at different stimulus frequencies shown in Fig. 3c. (c) Comparison of T1 and T2 at different stimulus frequencies shown in Fig. 3c. (d) Both a- and b-waves were observed in the ERG response evoked by the first stimulus flash. b1 and b2 show peak magnitude of ERG b-waves elicited by the first and subsequent stimulus flashes. Ta and Tb show the time delays, relative to the stimulus onset, of the a- and b-waves. (e) Comparison of b1 and b2 at different stimulus frequencies shown in Fig. 3c. (f) Comparison of Ta and Tb at different stimulus frequencies shown in Fig. 3c.
). Dynamic differential IOS images were constructed using the following equation [30

30. X. C. Yao, L. Liu, and Y. G. Li, “Intrinsic optical signal imaging of retinal activity in frog eye,” J. Inn. Opt. Health Scie. 2(02), 201–208 (2009). [CrossRef]

]:
IOSt(x,y)=It(x,y)Iref(x,y)Iref(x,y)
(1)
where It(x,y) was the intensity value of a pixel (x, y) at a time point t; Iref(x,y)was the dynamic reference baseline of m consecutive frames, which could be quantified by:
Iref(x,y)=i=tmi=t1Ii(x,y)m
(2)
In other words, the averaged pixel value of m consecutive frames recorded before the time point t was used as a reference baseline to calculate the differential IOS. For the dynamic differential IOSs shown in this article, we selected m = 100 (i.e., images recorded over 100 ms) for the dynamic reference baseline.

3. Results

Figure 3 compares concurrent IOS and ERG recordings of the frog retina activated by flicker stimuli from 1.0 to 6.0 Hz. The time courses of both IOS and ERG responses were tightly correlated with the flicker stimulus. In order to ensure the repeatability of the IOSs, two experimental trials were conducted at each stimulus frequency. The results shown in Fig. 3c and 3d indicate that both IOS and ERG responses were very repeatable. The experiments demonstrated that the dynamic differential IOSs can follow flicker stimuli up to at least 6 Hz. For higher frequency flickers (4 and 6 Hz), an additional OFF response (arrowheads in Fig. 3c) was detected in both IOS and ERG signals. For the 6 Hz flicker stimulus, the IOS and ERG OFF response reached their magnitude peaks at ~350 ms and ~325 ms after the onset of the last flash, respectively. Dynamic differential IOS imaging consistently showed positive and negative optical responses. Figure 3c shows that the fast IOSs in response to the first visible light flash was positive-going, and the fast IOSs elicited by the following flashes were negative-going IOSs. The peak magnitude (4.1-4.5%) and the time-to-peak (~120 ms) of the fast IOS response evoked by the first stimulus flash are almost constant across the stimulus frequencies (1-6 Hz). However, the magnitude and time delay of the IOS responses evoked by following flashes were gradually reduced with increasing stimulus frequency (Fig. 4b and 4c).

Similar changes were also observed in concurrent ERG recording (Fig. 3c). In each retinal flicker measurement, the first visible light flash typically evoked a rapid (time-to-peak: ~100 ms), but low magnitude, negative (decreasing) a-wave which was followed by a high magnitude positive (increasing) b-wave (Fig. 3c and Fig. 4d). The ERG signals elicited by the following flashes were mainly positive b-waves (Fig. 3c). The time-to-peak (~110 ms) of the ERG a-wave evoked by the first stimulus flash is constant across the stimulus frequencies (1-6 Hz). The peak magnitude (108-125 mV) and time-to-peak (~200 ms) of the first b-wave is also quite repeated (Fig. 3c). However, the magnitude and time delay of the ERG responses evoked by the following flashes were reduced with increasing stimulus frequency (Fig. 4e and 4f).

4. Discussion

Moreover, the different light sensitivities of rod- and cone-systems may also affect the spatial patterns of positive and negative IOSs. Because of the high light sensitivity of the rod-system, diffused visible light in the surrounding area may provide enough stimulation for the rod-system, but not for the cone-system. As shown in Fig. 2a and Fig. 3b, the negative IOSs were primarily confined in the center area of the stimulus, but positive IOSs could spread into a relatively larger area. We speculate that the first stimulus flash evoked IOSs in the dark-adapted retina, and acted as a light adaptation illumination for the following flashes. Therefore, the IOSs may be sensitive to the light adaptation condition. Further experiments with variable background light levels will allow better understanding of the IOS patterns evoked by flickers. It is well established that, in coordination with controlled light adaptation, flicker ERG can be used to dissect electrophysiological responses of different retinal cells, such as rod- and cone-dominated systems [28

28. N. S. Peachey, K. R. Alexander, D. J. Derlacki, and G. A. Fishman, “Light adaptation, rods, and the human cone flicker ERG,” Vis. Neurosci. 8(2), 145–150 (1992). [CrossRef] [PubMed]

, 41

41. T. E. Frumkes and T. Eysteinsson, “Suppressive rod-cone interaction in distal vertebrate retina: intracellular records from Xenopus and Necturus,” J. Neurophysiol. 57(5), 1361–1382 (1987). [PubMed]

, 42

42. T. E. Frumkes and S. M. Wu, “Independent influences of rod adaptation on cone-mediated responses to light onset and offset in distal retinal neurons,” J. Neurophysiol. 64(3), 1043–1054 (1990). [PubMed]

]. We anticipate that further development of IOS imaging of retinal flicker responses will lead to a new method for retinal diseases detection and treatment outcome evaluation.

Acknowledgements

This work is supported by DANA Foundation (Brain and Immuno-Imaging Grant Program), Eyesight Foundation of Alabama, and NIH (1R21RR025788-01).

References and links

1.

R. W. Nickells, “Ganglion cell death in glaucoma: from mice to men,” Vet. Ophthalmol. 10(s1Suppl 1), 88–94 (2007). [CrossRef] [PubMed]

2.

R. S. Harwerth and H. A. Quigley, “Visual field defects and retinal ganglion cell losses in patients with glaucoma,” Arch. Ophthalmol. 124(6), 853–859 (2006). [CrossRef] [PubMed]

3.

B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007). [CrossRef]

4.

Y. W. Qin, G. Z. Xu, and W. J. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006). [CrossRef] [PubMed]

5.

R. E. Hogg and U. Chakravarthy, “Visual function and dysfunction in early and late age-related maculopathy,” Prog. Retin. Eye Res. 25(3), 249–276 (2006). [CrossRef] [PubMed]

6.

H. P. Scholl and E. Zrenner, “Electrophysiology in the investigation of acquired retinal disorders,” Surv. Ophthalmol. 45(1), 29–47 (2000). [CrossRef] [PubMed]

7.

D. C. Hood, J. G. Odel, C. S. Chen, and B. J. Winn, “The multifocal electroretinogram,” J. Neuroophthalmol. 23(3), 225–235 (2003). [PubMed]

8.

D. C. Hood, “Assessing retinal function with the multifocal technique,” Prog. Retin. Eye Res. 19(5), 607–646 (2000). [CrossRef] [PubMed]

9.

B. J. Baker, H. Lee, V. A. Pieribone, L. B. Cohen, E. Y. Isacoff, T. Knopfel, and E. K. Kosmidis, “Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells,” J. Neurosci. Methods 161(1), 32–38 (2007). [CrossRef]

10.

M. Djurisic, M. Zochowski, M. Wachowiak, C. X. Falk, L. B. Cohen, and D. Zecevic, “Optical monitoring of neural activity using voltage-sensitive dyes,” Methods Enzymol. 361, 423–451 (2003). [CrossRef] [PubMed]

11.

L. B. Cohen, R. D. Keynes, and B. Hille, “Light scattering and birefringence changes during nerve activity,” Nature 218(5140), 438–441 (1968). [CrossRef] [PubMed]

12.

I. Tasaki, A. Watanabe, R. Sandlin, and L. Carnay, “Changes in fluorescence, turbidity, and birefringence associated with nerve excitation,” Proc. Natl. Acad. Sci. U.S.A. 61(3), 883–888 (1968). [CrossRef] [PubMed]

13.

K. P. Hofmann, R. Uhl, W. Hoffmann, and W. Kreutz, “Measurements on fast light-induced light-scattering and -absorption changes in outer segments of vertebrate light sensitive rod cells,” Biophys. Struct. Mech. 2(1), 61–77 (1976). [CrossRef] [PubMed]

14.

H. Kühn, N. Bennett, M. Michel-Villaz, and M. Chabre, “Interactions between photoexcited rhodopsin and GTP-binding protein: kinetic and stoichiometric analyses from light-scattering changes,” Proc. Natl. Acad. Sci. U.S.A. 78(11), 6873–6877 (1981). [CrossRef] [PubMed]

15.

M. Michel-Villaz, A. Brisson, Y. Chapron, and H. Saibil, “Physical analysis of light-scattering changes in bovine photoreceptor membrane suspensions,” Biophys. J. 46(5), 655–662 (1984). [CrossRef] [PubMed]

16.

H. H. Harary, J. E. Brown, and L. H. Pinto, “Rapid light-induced changes in near infrared transmission of rods in Bufo marinus,” Science 202(4372), 1083–1085 (1978). [CrossRef] [PubMed]

17.

D. R. Pepperberg, M. Kahlert, A. Krause, and K. P. Hofmann, “Photic modulation of a highly sensitive, near-infrared light-scattering signal recorded from intact retinal photoreceptors,” Proc. Proc. Natl. Acad. Sci. 85(15), 5531–5535 (1988). [CrossRef]

18.

X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005). [CrossRef] [PubMed]

19.

K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, “Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography,” Proc. Natl. Acad. Sci. U.S.A. 103(13), 5066–5071 (2006). [CrossRef] [PubMed]

20.

V. J. Srinivasan, M. Wojtkowski, J. G. Fujimoto, and J. S. Duker, “In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography,” Opt. Lett. 31(15), 2308–2310 (2006). [CrossRef] [PubMed]

21.

V. J. Srinivasan, Y. Chen, J. S. Duker, and J. G. Fujimoto, “In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT,” Opt. Express 17(5), 3861–3877 (2009). [CrossRef] [PubMed]

22.

K. Grieve and A. Roorda, “Intrinsic signals from human cone photoreceptors,” Invest. Ophthalmol. Vis. Sci. 49(2), 713–719 (2008). [CrossRef] [PubMed]

23.

R. S. Jonnal, J. Rha, Y. Zhang, B. Cense, W. H. Gao, and D. T. Miller, “In vivo functional imaging of human cone photoreceptors,” Opt. Express 15(24), 16141–16160 (2007). [CrossRef] [PubMed]

24.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005). [PubMed]

25.

M. D. Abràmoff, Y. H. Kwon, D. Ts’o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, “Visual stimulus-induced changes in human near-infrared fundus reflectance,” Invest. Ophthalmol. Vis. Sci. 47(2), 715–721 (2006). [CrossRef] [PubMed]

26.

J. L. Schei, M. D. McCluskey, A. J. Foust, X. C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008). [CrossRef] [PubMed]

27.

X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008). [CrossRef] [PubMed]

28.

N. S. Peachey, K. R. Alexander, D. J. Derlacki, and G. A. Fishman, “Light adaptation, rods, and the human cone flicker ERG,” Vis. Neurosci. 8(2), 145–150 (1992). [CrossRef] [PubMed]

29.

P. A. Sieving, K. Murayama, and F. Naarendorp, “Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave,” Vis. Neurosci. 11(3), 519–532 (1994). [CrossRef] [PubMed]

30.

X. C. Yao, L. Liu, and Y. G. Li, “Intrinsic optical signal imaging of retinal activity in frog eye,” J. Inn. Opt. Health Scie. 2(02), 201–208 (2009). [CrossRef]

31.

X. C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005). [CrossRef] [PubMed]

32.

X. C. Yao, D. M. Rector, and J. S. George, “Optical lever recording of displacements from activated lobster nerve bundles and Nitella internodes,” Appl. Opt. 42(16), 2972–2978 (2003). [CrossRef] [PubMed]

33.

I. Tasaki and P. M. Byrne, “Rapid structural changes in nerve fibers evoked by electric current pulses,” Biochem. Biophys. Res. Commun. 188(2), 559–564 (1992). [CrossRef] [PubMed]

34.

L. B. Cohen, “Changes in neuron structure during action potential propagation and synaptic transmission,” Physiol. Rev. 53(2), 373–418 (1973). [PubMed]

35.

G. H. Kim, P. Kosterin, A. L. Obaid, and B. M. Salzberg, “A Mechanical Spike Accompanies the Action Potential in Mammalian Nerve Terminals,” Biophys. J. (2007).

36.

A. J. Foust and D. M. Rector, “Optically teasing apart neural swelling and depolarization,” Neuroscience 145(3), 887–899 (2007). [CrossRef] [PubMed]

37.

B. M. Salzberg, A. L. Obaid, and H. Gainer, “Large and rapid changes in light scattering accompany secretion by nerve terminals in the mammalian neurohypophysis,” J. Gen. Physiol. 86(3), 395–411 (1985). [CrossRef] [PubMed]

38.

D. Landowne, “Measuring nerve excitation with polarized light,” Jpn. J. Physiol. 43(Suppl 1), S7–S11 (1993). [PubMed]

39.

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991). [CrossRef] [PubMed]

40.

S. M. Dawis and M. Rossetto, “Light-evoked changes in near-infrared transmission by the ON and OFF channels of the anuran retina,” Vis. Neurosci. 10(4), 687–692 (1993). [CrossRef] [PubMed]

41.

T. E. Frumkes and T. Eysteinsson, “Suppressive rod-cone interaction in distal vertebrate retina: intracellular records from Xenopus and Necturus,” J. Neurophysiol. 57(5), 1361–1382 (1987). [PubMed]

42.

T. E. Frumkes and S. M. Wu, “Independent influences of rod adaptation on cone-mediated responses to light onset and offset in distal retinal neurons,” J. Neurophysiol. 64(3), 1043–1054 (1990). [PubMed]

OCIS Codes
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(330.4270) Vision, color, and visual optics : Vision system neurophysiology
(330.5310) Vision, color, and visual optics : Vision - photoreceptors
(330.5380) Vision, color, and visual optics : Physiology

ToC Category:
Vision, Color, and Visual Optics

History
Original Manuscript: December 16, 2009
Revised Manuscript: February 11, 2010
Manuscript Accepted: February 23, 2010
Published: March 24, 2010

Virtual Issues
Vol. 5, Iss. 7 Virtual Journal for Biomedical Optics

Citation
Yang-Guo Li, Qiu-Xiang Zhang, Lei Liu, Franklin R. Amthor, and Xin-Cheng Yao, "High spatiotemporal resolution imaging of fast intrinsic optical signals activated by retinal flicker stimulation," Opt. Express 18, 7210-7218 (2010)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-18-7-7210


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References

  1. R. W. Nickells, “Ganglion cell death in glaucoma: from mice to men,” Vet. Ophthalmol. 10(s1Suppl 1), 88–94 (2007). [CrossRef] [PubMed]
  2. R. S. Harwerth and H. A. Quigley, “Visual field defects and retinal ganglion cell losses in patients with glaucoma,” Arch. Ophthalmol. 124(6), 853–859 (2006). [CrossRef] [PubMed]
  3. B. Meyer-Rüsenberg, M. Pavlidis, T. Stupp, and S. Thanos, “Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 245(7), 1009–1018 (2007). [CrossRef]
  4. Y. W. Qin, G. Z. Xu, and W. J. Wang, “Dendritic abnormalities in retinal ganglion cells of three-month diabetic rats,” Curr. Eye Res. 31(11), 967–974 (2006). [CrossRef] [PubMed]
  5. R. E. Hogg and U. Chakravarthy, “Visual function and dysfunction in early and late age-related maculopathy,” Prog. Retin. Eye Res. 25(3), 249–276 (2006). [CrossRef] [PubMed]
  6. H. P. Scholl and E. Zrenner, “Electrophysiology in the investigation of acquired retinal disorders,” Surv. Ophthalmol. 45(1), 29–47 (2000). [CrossRef] [PubMed]
  7. D. C. Hood, J. G. Odel, C. S. Chen, and B. J. Winn, “The multifocal electroretinogram,” J. Neuroophthalmol. 23(3), 225–235 (2003). [PubMed]
  8. D. C. Hood, “Assessing retinal function with the multifocal technique,” Prog. Retin. Eye Res. 19(5), 607–646 (2000). [CrossRef] [PubMed]
  9. B. J. Baker, H. Lee, V. A. Pieribone, L. B. Cohen, E. Y. Isacoff, T. Knopfel, and E. K. Kosmidis, “Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells,” J. Neurosci. Methods 161(1), 32–38 (2007). [CrossRef]
  10. M. Djurisic, M. Zochowski, M. Wachowiak, C. X. Falk, L. B. Cohen, and D. Zecevic, “Optical monitoring of neural activity using voltage-sensitive dyes,” Methods Enzymol. 361, 423–451 (2003). [CrossRef] [PubMed]
  11. L. B. Cohen, R. D. Keynes, and B. Hille, “Light scattering and birefringence changes during nerve activity,” Nature 218(5140), 438–441 (1968). [CrossRef] [PubMed]
  12. I. Tasaki, A. Watanabe, R. Sandlin, and L. Carnay, “Changes in fluorescence, turbidity, and birefringence associated with nerve excitation,” Proc. Natl. Acad. Sci. U.S.A. 61(3), 883–888 (1968). [CrossRef] [PubMed]
  13. K. P. Hofmann, R. Uhl, W. Hoffmann, and W. Kreutz, “Measurements on fast light-induced light-scattering and -absorption changes in outer segments of vertebrate light sensitive rod cells,” Biophys. Struct. Mech. 2(1), 61–77 (1976). [CrossRef] [PubMed]
  14. H. Kühn, N. Bennett, M. Michel-Villaz, and M. Chabre, “Interactions between photoexcited rhodopsin and GTP-binding protein: kinetic and stoichiometric analyses from light-scattering changes,” Proc. Natl. Acad. Sci. U.S.A. 78(11), 6873–6877 (1981). [CrossRef] [PubMed]
  15. M. Michel-Villaz, A. Brisson, Y. Chapron, and H. Saibil, “Physical analysis of light-scattering changes in bovine photoreceptor membrane suspensions,” Biophys. J. 46(5), 655–662 (1984). [CrossRef] [PubMed]
  16. H. H. Harary, J. E. Brown, and L. H. Pinto, “Rapid light-induced changes in near infrared transmission of rods in Bufo marinus,” Science 202(4372), 1083–1085 (1978). [CrossRef] [PubMed]
  17. D. R. Pepperberg, M. Kahlert, A. Krause, and K. P. Hofmann, “Photic modulation of a highly sensitive, near-infrared light-scattering signal recorded from intact retinal photoreceptors,” Proc. Proc. Natl. Acad. Sci. 85(15), 5531–5535 (1988). [CrossRef]
  18. X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005). [CrossRef] [PubMed]
  19. K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, “Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography,” Proc. Natl. Acad. Sci. U.S.A. 103(13), 5066–5071 (2006). [CrossRef] [PubMed]
  20. V. J. Srinivasan, M. Wojtkowski, J. G. Fujimoto, and J. S. Duker, “In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography,” Opt. Lett. 31(15), 2308–2310 (2006). [CrossRef] [PubMed]
  21. V. J. Srinivasan, Y. Chen, J. S. Duker, and J. G. Fujimoto, “In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT,” Opt. Express 17(5), 3861–3877 (2009). [CrossRef] [PubMed]
  22. K. Grieve and A. Roorda, “Intrinsic signals from human cone photoreceptors,” Invest. Ophthalmol. Vis. Sci. 49(2), 713–719 (2008). [CrossRef] [PubMed]
  23. R. S. Jonnal, J. Rha, Y. Zhang, B. Cense, W. H. Gao, and D. T. Miller, “In vivo functional imaging of human cone photoreceptors,” Opt. Express 15(24), 16141–16160 (2007). [CrossRef] [PubMed]
  24. D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005). [PubMed]
  25. M. D. Abràmoff, Y. H. Kwon, D. Ts’o, P. Soliz, B. Zimmerman, J. Pokorny, and R. Kardon, “Visual stimulus-induced changes in human near-infrared fundus reflectance,” Invest. Ophthalmol. Vis. Sci. 47(2), 715–721 (2006). [CrossRef] [PubMed]
  26. J. L. Schei, M. D. McCluskey, A. J. Foust, X. C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008). [CrossRef] [PubMed]
  27. X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008). [CrossRef] [PubMed]
  28. N. S. Peachey, K. R. Alexander, D. J. Derlacki, and G. A. Fishman, “Light adaptation, rods, and the human cone flicker ERG,” Vis. Neurosci. 8(2), 145–150 (1992). [CrossRef] [PubMed]
  29. P. A. Sieving, K. Murayama, and F. Naarendorp, “Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave,” Vis. Neurosci. 11(3), 519–532 (1994). [CrossRef] [PubMed]
  30. X. C. Yao, L. Liu, and Y. G. Li, “Intrinsic optical signal imaging of retinal activity in frog eye,” J. Inn. Opt. Health Scie. 2(02), 201–208 (2009). [CrossRef]
  31. X. C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005). [CrossRef] [PubMed]
  32. X. C. Yao, D. M. Rector, and J. S. George, “Optical lever recording of displacements from activated lobster nerve bundles and Nitella internodes,” Appl. Opt. 42(16), 2972–2978 (2003). [CrossRef] [PubMed]
  33. I. Tasaki and P. M. Byrne, “Rapid structural changes in nerve fibers evoked by electric current pulses,” Biochem. Biophys. Res. Commun. 188(2), 559–564 (1992). [CrossRef] [PubMed]
  34. L. B. Cohen, “Changes in neuron structure during action potential propagation and synaptic transmission,” Physiol. Rev. 53(2), 373–418 (1973). [PubMed]
  35. G. H. Kim, P. Kosterin, A. L. Obaid, and B. M. Salzberg, “A Mechanical Spike Accompanies the Action Potential in Mammalian Nerve Terminals,” Biophys. J. (2007).
  36. A. J. Foust and D. M. Rector, “Optically teasing apart neural swelling and depolarization,” Neuroscience 145(3), 887–899 (2007). [CrossRef] [PubMed]
  37. B. M. Salzberg, A. L. Obaid, and H. Gainer, “Large and rapid changes in light scattering accompany secretion by nerve terminals in the mammalian neurohypophysis,” J. Gen. Physiol. 86(3), 395–411 (1985). [CrossRef] [PubMed]
  38. D. Landowne, “Measuring nerve excitation with polarized light,” Jpn. J. Physiol. 43(Suppl 1), S7–S11 (1993). [PubMed]
  39. R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991). [CrossRef] [PubMed]
  40. S. M. Dawis and M. Rossetto, “Light-evoked changes in near-infrared transmission by the ON and OFF channels of the anuran retina,” Vis. Neurosci. 10(4), 687–692 (1993). [CrossRef] [PubMed]
  41. T. E. Frumkes and T. Eysteinsson, “Suppressive rod-cone interaction in distal vertebrate retina: intracellular records from Xenopus and Necturus,” J. Neurophysiol. 57(5), 1361–1382 (1987). [PubMed]
  42. T. E. Frumkes and S. M. Wu, “Independent influences of rod adaptation on cone-mediated responses to light onset and offset in distal retinal neurons,” J. Neurophysiol. 64(3), 1043–1054 (1990). [PubMed]

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