Abstract
Purpose :
Light-evoked intrinsic optical signal (IOS) promises a noninvasive biomarker for objective assessment of retinal physiological function. This study demonstrates longitudinal IOS monitoring of photoreceptor development in wild type (WT) mice and comparative photoreceptor dysfunction in retinal degeneration mice.
Methods :
WT (C57BL/6J) and retinal degeneration 10 (rd10) mice at postnatal day (P) 14, P17, P21, and P28 were used in this study. A custom-built optical coherence tomography (OCT) system, providing 3 μm resolution of both axial and lateral directions, was used for retinal IOS imaging. Comparative full-field electroretinography (ERG) was implemented. A 10 ms green flash was delivered to the dark-adapted retina to elicit IOS response. For quantitative analysis, active-IOS pixels were extracted by a pixelwise OCT signal comparison between pre-stimulus and post-stimulus (Fig. 1A). Histological examination was also performed to correlate morphological change in the retina.
Results :
At P14, similar photoreceptor-IOS response was observed in WT and rd10 mice (Fig. 1B1). However, the IOS response was significantly larger in WT, compared to rd10, from P17 (WT’s active IOS: 79 ± 9.8; rd10’s active IOS: 25.8 ± 9.4; P < .001). Active IOS pixels in WT continued to increase with photoreceptor development and reached the maximum response level at P28. In contrary, there was no robust IOS observed in rd10 at P28, due to photoreceptor degeneration (Fig. 1B1). Active-IOS pixels were consistently observed between the interdigitation zone and the retinal pigment epithelium (RPE) (Fig. 1A). The ERG a-wave at P14 was comparable between WT (a-wave: 0.19 ± 0.02 mV) and rd10 (a-wave: 0.19 ± 0.01 mV). The a-wave amplitude of WT was gradually increased with age and saturated at P21; while the a-wave of rd10 was negatively correlated with age.
Conclusions :
Comparative IOS imaging of WT and rd10 indicates that the photoreceptor-IOS is highly sensitive to the photoreceptors’ maturity and functional integrity. Shrinkage-induced conformational change of rod outer segments is speculated to be the primary source of the photoreceptor-IOS response, and its onset time is clearly before the hyperpolarization of the photoreceptor. Further development of the functional IOS imaging promises an objective method for early detection of age-related macular degeneration (AMD) and retinitis pigmentosa (RP) that are known to produce photoreceptor dysfunctions.
This is a 2020 ARVO Annual Meeting abstract.