Purpose:
The purpose of this study is to compare intrinsic optical signal (IOS) changes in normal and mutant retinas, and therefore to demonstrate the potential of IOS mapping of diseases associated retinal dysfunctions. The retinal degeneration model chosen for study is the Cngb1 knockout mouse that initially exhibits attenuated rod function and gradually loses all rod function within 8 months.
Methods:
A near infared (NIR) microscope equipped with high speed (1000 frames/s) CMOS camera was employed to achieve dynamic IOS imaging of retinal response evoked by a 10-ms visible light flash. Freshly isolated (intact and living) mouse (Mus musculus) retinas(without RPE) were used for this study. Both two-month old and one-year old mice were investigated. During the experiment, the retina was continuously super-fused (~2ml/min) with oxygenated bicarbonate-buffered Ames medium, maintained at pH 7.4 and 33~37°C. Stimulus-evoked IOS changes in wild-type (WT) and Cngb1 knockout mutant mouse (Mus musculus) retinas were quantitatively compared.
Results:
In two-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 time matched WT mice(Figs. b-d). In one-year old mutant mice, stimulus-evoked IOS was totally absent. However, enhanced spontaneous activities, which might reflect inner neural remodeling in diseased retina, were observed in both two-month and one-year old mutant retinas (Figs. c-d).
Conclusions:
Unambiguous IOS abnormalities were observed in mutant mice. Our experiments demonstrate the potential of using IOS imaging for noninvasive and high resolution identification of diseased associated retinal dysfunctions. Moreover, high spatiotemporal resolution IOS imaging may lead to advanced understanding of diseases associated with neural remodeling in the retina.
Keywords: retinal connections, networks, circuitry • photoreceptors • retinal degenerations: cell biology