Abstract
Rapid dilation of retinal vessels in response to flickering light (functional hyperemia) is a well-known autoregulatory response driven by increased neural activity in the inner retina. Little is known about flicker-induced changes of activity of retinal neurons themselves. We non-invasively investigated flicker-induced changes of retinal ganglion cell (RGC) function in common inbred mouse strains using the pattern electroretinogram (PERG), a sensitive measure of RGC function. Flicker was superimposed on the pattern stimulus at frequencies that did not generate measurable flicker-ERG and alter the PERG response. Transition from flicker at 101 Hz (control) to flicker at 11 Hz (test) at constant mean luminance induced a slow reduction of PERG amplitude to a minimum (39% loss in C57BL/6J mice and 52% loss in DBA/2J mice) 4–5 minutes after 11 Hz flicker onset, followed by a slow recovery to baseline over 20 minutes. Results demonstrate that the magnitude and temporal dynamics of RGC response induced by flicker at 11 Hz can be non-invasively assessed with PERG in the mouse. This allows investigating the functional phenotype of different mouse strains as well as pathological changes in glaucoma and optic nerve disease. The non-contact flicker-PERG method opens the possibility of combined assessment of neural and vascular response dynamics.
Highlights
Rapid dilation of retinal vessels in response to flickering light is a well-known autoregulatory response driven by increased neural activity in the inner retina
Generalized Estimating Equation (GEE) statistics for longitudinal data using pattern electroretinogram (PERG) amplitude as dependent variable and test period (PERG #1,2,3,4) and strain (B6, D2) as predictor variables revealed a strong effect of period (P < 0.0001), no significant effect of strain (P = 0.35), but a strong interaction between period and strain (P < 0.001)
As a control that the results were not biased by progressive decrease of amplitude with time due to unrelated factors such anesthesia level, we recorded in different B6 mice and D2 mice (N = 4 for each group) sequential PERGs with constant superimposition of 101 Hz flicker
Summary
Rapid dilation of retinal vessels in response to flickering light (functional hyperemia) is a well-known autoregulatory response driven by increased neural activity in the inner retina. Results demonstrate that the magnitude and temporal dynamics of RGC response induced by flicker at 11 Hz can be non-invasively assessed with PERG in the mouse. This allows investigating the functional phenotype of different mouse strains as well as pathological changes in glaucoma and optic nerve disease. Rapid dilation of retinal vessels in response to flickering light (functional hyperemia) is a well-known autoregulatory response[1,2,3] that is believed to reflect an increase in blood flow to meet the increased metabolic demand of activated amacrine cells and ganglion cells (RGC) in the inner retina[1]. We non-invasively investigate flicker-induced changes of RGC function in common inbred mouse strains
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