Comparative intrinsic optical signal imaging of wild-type and mutant mouse retinas

Abstract

Functional measurement is important for retinal study and disease diagnosis. Transient intrinsic optical signal (IOS) response, tightly correlated with functional stimulation, has been previously detected in normal retinas. In this paper, comparative IOS imaging of wild-type (WT) and rod-degenerated mutant mouse retinas is reported. Both 2-month and 1-year-old mice were measured. In 2-month-old mutant mice, time course and peak value of the stimulus-evoked IOS were significantly delayed (relative to stimulus onset) and reduced, respectively, compared to age matched WT mice. In 1-year-old mutant mice, stimulus-evoked IOS was totally absent. However, enhanced spontaneous IOS responses, which might reflect inner neural remodeling in diseased retina, were observed in both 2-month and 1-year-old mutant retinas. Our experiments demonstrate the potential of using IOS imaging for noninvasive and high resolution identification of disease-associated retinal dysfunctions. Moreover, high spatiotemporal resolution IOS imaging may also lead to advanced understanding of disease-associated neural remodeling in the retina.

Dynamic near-infrared imaging reveals transient phototropic change in retinal rod photoreceptors

“…3 indicate that the transient phototropic changes can partially contribute to IOS recording, which has the potential to be developed into a superior noninvasive method for spatiotemporal mapping of retinal function. 8,10 The different time courses of the IOSs at Zone 1 (periphery) and Zone 2 (center) suggest that the phototropic change of rod photoreceptors primarily contributes to the periphery IOS response. Multiple IOS origins, including neurotransmitter secretion, 32 refractive index change of neural tissues, 33 interactions between photoexcited rhodopsin and guanosine triphosphate (GTP)-binding protein, 34 disc shape change, 35 cell swelling, 36 etc., have been proposed.…”

“…10 A fast digital camera (Neo sCMOS, Andor Technology, Belfast, UK) with pixel size 6 × 6 μm 2 was used for retinal imaging. A 20× water immersion objective with 0.5 NA was used for frog experiments.…”

“…The three-sigma rule was used to set up a threshold to distinguish silent and active photoreceptors. 10 If the stimulus-evoked photoreceptor shifted above this threshold, then this photoreceptor was defined as active. Otherwise, it was defined as silent.…”

“…9 Protocols for handling mouse samples were previously reported. 10 Briefly, after the eyeball was enucleated from anesthetized mice, the retina was isolated from the eyeball in Ames media and then transferred to a recording chamber. During the experiment, the sample was continuously superfused with oxygenated bicarbonate-buffered Ames medium, maintained at pH 7.4 and 33°C to 37°C.…”

In vivooptical coherence tomography of stimulus-evoked intrinsic optical signals in mouse retinas

“…13,28 In vitro IOS imaging of normal and mutant mouse retinas has been conducted to demonstrate disease-produced IOS distortions. 30 Laser-injured frog eyes have been used to demonstrate in vivo IOS mapping of localized retinal dysfunction. 27 Both in vitro and in vivo studies have shown that fast IOSs have different polarities and mainly originate from the photoreceptor outer segments in frog retinas.…”