During the past year, we investigated effects of light adaptation on mouse photopic electroretinogram (ERG) responses. It is well-known that light adaptation alters cone mediated photopic ERG responses. To elucidate the mechanisms that mediating light-dependent changes in photopic ERG responses, we investigated effect of light adaptation on mouse photopic ERG and tested hypothesis that changes in ERG amplitude during light adaptation reflect the modulation of rod-cone coupling in retina. After over-night dark-adaptation, mouse ERG responses to a series of flash intensity were recorded using Espion system at 0, 5, 10, and 15 min after onset of adaptation light (20 cd/m2). Semisaturation constants (K) and maximum response amplitude (Rmax) were derived by fitting intensity-response data to Naka-Rushton equation. A band-pass (40-200 Hz) digital filter was used to isolate oscillatory potentials (OP). Light adaptation changes both sensitivity and maximum amplitude of photopic ERG recorded from wildtype mice (C57BL/6J). For photopic responses elicited by green flashes at 0, 5, 10, and 15 min after light adaptation, K and Rmax were 1.54, 2.28, 2.75, and 3.65 cd.s/m2 and 95.9, 148.4, 182.2 and 218.1V, respectively. The same light adaptation had minimal effects on sensitivity for ERG responses elicited with UV flashes (K values of 2.31, 2.90, 2.76, and 2.99 x103 photons/m2, respectively), but with similar enhancement for Rmax (91.8, 149.5, 182.3, and 220 V, respectively). The contribution of OP in mouse photopic ERG was only slightly reduced during the light adaptation. The ratios of summed OP to b-wave were 1.080.13, 1.060.10, 0.950.07, and 0.840.07, respectively, for responses elicited by 100 cd.s/m2 flashes. Compare with WT mice, the enhancements of response by light adaptation were greatly reduced in connexin36 knock out (Cx36KO) mice. Ratio of Rmax after 15 min light adaptation to those recorded at onset of light (light adaptation enhancement factor, LAEF) was 2.640.29 (n=5) for WT and 1.060.04 (n=4) for Cx36KO mice. Intraocular injection of meclofenamic acid (MFA), a gap junction blocker, also significantly reduced LAEF to 1.130.06 (n=3). LAEF depends on duration of prior dark-adaptation, with values of 1.550.21 (n=4) and 1.830.05 (n=4) for 30min and 1hr dark adaptation, respectively. In conclusion, our results indicate that, in addition to the reduction in sensitivity, light adaptation also enhances response amplitude for mouse photopic ERG. Enhancement of response amplitude is likely mediated by reduction of rod-cone coupling during the light adaptation. Our study provided a novel approach to noninvasively measure dynamics of rod-cone gap junction in intact eyes.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000530-06
Application #
9795936
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
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