Quantification of microvascular change of retinal degeneration in Royal College of Surgeons rats using high-resolution spectral domain optical coherence tomography angiography.

Significance: For research on retinitis pigmentosa in humans, the Royal College of Surgeons (RCS) rat is commonly used as the primary animal model since the disease process is similar. Therefore, it is necessary to understand how the disease develops and determine whether the treatment is effective. Aim: In this study, structural and microvascular change of retinal degeneration in RCS rats was assessed non-invasively on specific dates over 3.5 months. Approach: Using a high-resolution spectral domain (SD) optical coherence tomography angiography (OCTA), the retinal degeneration in RCS rats, from day 14 until day 126, was qualitatively and quantitatively analyzed. Results: Aside from the thinning of the retina thickness starting from 2 weeks of age, blood vessels in the deep layer of the retina also began to degenerate at about 4 weeks of age. Hole structures appeared at the inner nuclear layer and the inner plexiform layer by the age of 10 weeks. Observations of abnormal angiogenesis in the choroid began by 12 weeks of age. Conclusions: We conducted a longitudinal study of retina degeneration structure and vascular changes in an RCS rat model using a supercontinuum laser based high-resolution SD-OCTA. Combined with OCTA, OCT leads to a better understanding of photoreceptor pathology as retinal degeneration by identifying tissue and vessel loss.

Inhibition of DUSP6 Activates Autophagy and Rescues the Retinal Pigment Epithelium in Sodium Iodate-Induced Retinal Degeneration Models In Vivo and In Vitro.

Autophagy plays a protective role in the retinal pigment epithelium (RPE) by eliminating damaged organelles in response to reactive oxygen species (ROS). Dual-specificity protein phosphatase 6 (DUSP6), which belongs to the DUSP subfamily, works as a negative-feedback regulator of the extracellular signal-regulated kinase (ERK) pathway. However, the complex interplay between DUSP6 and autophagy induced by ROS in RPE is yet to be investigated. To investigate the relationship between DUSP6 and autophagy, we exposed the ARPE-19 cell line and C57BL/6N mice to sodium iodate (NaIO3) as an oxidative stress inducer. Our data showed that the inhibition of DUSP6 activity promotes autophagy flux through the ERK pathway via the upregulation of immunoblotting expression in ARPE-19 cells. Live imaging showed a significant increase in autophagic flux activities, which suggested the restoration autophagy after treatment with the DUSP6 inhibitor. Furthermore, the mouse RPE layer exhibited an irregular structure and abnormal deposits following NaIO3 injection. The retina layer was recovered after being treated with DUSP6 inhibitor; this suggests that DUSP6 inhibitor can rescue retinal damage by restoring the mouse retina's autophagy flux. This study suggests that the upregulation of DUSP6 can cause autophagy flux malfunctions in the RPE. The DUSP6 inhibitor can restore autophagy induction, which may serve as a potential therapeutic approach for retinal degeneration disease.

The use of intensity-based Doppler variance method for single vessel response to functional neurovascular activation.

This study presents 1 use of optical coherence tomography (OCT) angiography technique to examine neurovascular coupling effect. Repeated B-scans OCT recording is performed on the rat somatosensory cortex with cranial window preparation while its contralateral forepaw is electrically stimulated to activate the neurons in rest. We use an intensity-based Doppler variance (IBDV) algorithm mapped cerebral blood vessels in the cortex, and the temporal alteration in blood perfusion during neurovascular activation is analyzed using the proposed IBDV quantitative parameters. By using principal component analysis-based Fuzzy C Means clustering method, the stimulus-evoked vasomotion patterns were classified into 3 categories. We found that the response time of small vessels (resting diameter 14.9 ±6.6 µm), middle vessels (resting diameter 21.1 ±7.9 µm) and large vessels (resting diameter 50.7 ±6.5 µm) to achieve 5% change of vascular dilation after stimulation was 1.5, 2 and 5.5 seconds, respectively. Approximately 5% peak change of relative blood flow (RBF) in both small and middle vessels was observed. The large vessels react slowly and their responses nearly 4 seconds delayed, but no significant change in RBF of the large vessels was seen.

Supercontinuum source-based multi-contrast optical coherence tomography for rat retina imaging.

This study proposed an ultrahigh-resolution multi-contrast optical coherence tomography system integrated with fundus photography for in vivo retinal imaging of rodents. A supercontinuum light source was used in the system, providing an axial resolution of less than 3 µm within 1.8 mm (in the tissue). Three types of tissue contrast based on backscattered intensity, phase retardation, and microvasculature at a capillary level can be simultaneously obtained using the proposed system. Pigmented Long-Evans, non-pigmented (albino) Sprague Dawley, and Royal College of Surgeons rats were imaged and compared. In vivo imaging results were validated with histology.