The Origins of Stimulus Dependent Intrinsic Optical Signals of the Retina

Abstract

Abstract: : Purpose: To better characterize the sources of functionally correlated intrinsic optical signals in the intact retina. Methods: Intrinsic optical signals of cat retina in vivo were recorded and imaged with a cooled CCD camera attached to a modified fundus camera. Retinal images in the near–infrared (700–900nm) were collected, while a visible (550nm) checkboard pattern stimulus was delivered to the retina. ERG/PERG/VEP recordings were performed to correlate the strength and characteristics of the intrinsic optical signals with an independent measure of retinal activity. Results: Multiple intrinsic signals were observed, depending on retinal location, that differed in amplitude and sign. Particularly striking was the presence of a positive (increase in reflectance) signal that was often spatially offset to the negative signal, and may reflect the architecture of the underlying retinal circulation. The asymmetric pattern of the positive and negative signal response, elicited with an increase in luminance over background, was found to invert with a decrease in luminance over background. Using stimuli at either 450nm or 550nm revealed that 450nm stimuli are similarly effective compared with 550nm in stimulating these optical signal responses, which suggests a significant rod or melanopsin component. By varying the illumination wavelengths, we have measured the action spectra of the optical signal response, which shows a monotonic decrease in fractional reflectance change from 700 to 900nm, including 805nm, a hemoglobin isobestic wavelength. The optical signal response was also found to increase linearly with increasing stimulus duration from 200ms to 10seconds. To determine the extent of ganglion cell layer contribution, optical and electrical recordings were performed before and after intravitreal injections of TTX. Preliminary results indicate that a significant component of the optical signal response survives the TTX injection, and, combined with other evidence, suggests an outer retinal origin of a portion of the optical signal response. Conclusions: These findings suggest that a significant component of the observed signal originates from outer retinal sources, with a contribution from the rods, or possibly from melanopsin cells. The action spectra data are consistent with a significant hemoglobin/blood volume component, and supplements other evidence supporting a component of these signals arising from hemodynamic sources.

Keywords: blood supply • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • retinal connections, networks, circuitry