Safety and efficacy of human Wharton's Jelly-derived mesenchymal stem cells therapy for retinal degeneration

Purpose To investigate the safety and efficacy of subretinal injection of human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. Methods RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. Results No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. Conclusions Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies

Fractal Dimension Analysis of Transient Visual Evoked Potentials: Optimisation and Applications

Purpose The visual evoked potential (VEP) provides a time series signal response to an external visual stimulus at the location of the visual cortex. The major VEP signal components, peak latency and amplitude, may be affected by disease processes. Additionally, the VEP contains fine detailed and non-periodic structure, of presently unclear relevance to normal function, which may be quantified using the fractal dimension. The purpose of this study is to provide a systematic investigation of the key parameters in the measurement of the fractal dimension of VEPs, to develop an optimal analysis protocol for application. Methods VEP time series were mathematically transformed using delay time, τ, and embedding dimension, m, parameters. The fractal dimension of the transformed data was obtained from a scaling analysis based on straight line fits to the numbers of pairs of points with separation less than r versus log(r) in the transformed space. Optimal τ, m, and scaling analysis were obtained by comparing the consistency of results using different sampling frequencies. The optimised method was then piloted on samples of normal and abnormal VEPs. Results Consistent fractal dimension estimates were obtained using τ = 4 ms, designating the fractal dimension = D2 of the time series based on embedding dimension m = 7 (for 3606 Hz and 5000 Hz), m = 6 (for 1803 Hz) and m = 5 (for 1000Hz), and estimating D2 for each embedding dimension as the steepest slope of the linear scaling region in the plot of log(C(r)) vs log(r) provided the scaling region occurred within the middle third of the plot. Piloting revealed that fractal dimensions were higher from the sampled abnormal than normal achromatic VEPs in adults (p = 0.02). Variances of fractal dimension were higher from the abnormal than normal chromatic VEPs in children (p = 0.01). Conclusions A useful analysis protocol to assess the fractal dimension of transformed VEPs has been developed

Test-Retest Repeatability of Microperimetry at the Border of Deep Scotomas

Citation: Wu Z, Jung CJ, Ayton LN, Luu CD, Guymer RH. Test-retest repeatability of microperimetry at the border of deep scotomas. Invest Ophthalmol Vis Sci. 2015;56:2606-2611. DOI:10.1167/iovs.14-15977 PURPOSE. The purpose of this study was to examine the test-retest repeatability of microperimetric sensitivity at the border of deep scotomas. METHODS. Thirty normal participants underwent two examinations, each on the Macular Integrity Assessment (MAIA) microperimeter and on the MP-1 microperimeter (four examinations in total). A customized stimulus pattern allowed microperimetric sensitivity to be measured at the border of the optic nerve head (ONH), which acted as a model for the border of a deep scotoma-and also at the macular and peripapillary region. RESULTS. There were no significant changes in average point-wise sensitivity (PWS) values between the two examinations for all three regions using the MAIA microperimeter (P ‡ 0.262). The PWS coefficient of repeatability (CoR) was 612.99 dB at the border of the ONH, which was significantly larger than points in the macular and peripapillary regions (P > 0.001). A significant decrease in average PWS, using the MP-1 microperimeter at the macular and peripapillary region (P < 0.001), meant that the PWS CoR could not be determined in these regions. No significant changes in average PWS were observed at the border of the ONH (P ¼ 0.223), and the PWS CoR was 67.52 dB in this region. CONCLUSIONS. Microperimetric test-retest repeatability at the border of a deep scotoma was worse than at other areas of normal retina, and this highlights the limitation of applying a single estimate of test-retest repeatability to determine whether significant functional decline has occurred at the border of a deep scotoma

Beyond Disentangled Representations: An Attentive Angular Distillation Approach to Large-scale Lightweight Age-Invariant Face Recognition

Disentangled representations have been commonly adopted to Age-invariant Face Recognition (AiFR) tasks. However, these methods have reached some limitations with (1) the requirement of large-scale face recognition (FR) training data with age labels, which is limited in practice; (2) heavy deep network architecture for high performance; and (3) their evaluations are usually taken place on age-related face databases while neglecting the standard large-scale FR databases to guarantee its robustness. This work presents a novel Attentive Angular Distillation (AAD) approach to Large-scale Lightweight AiFR that overcomes these limitations. Given two high-performance heavy networks as teachers with different specialized knowledge, AAD introduces a learning paradigm to efficiently distill the age-invariant attentive and angular knowledge from those teachers to a lightweight student network making it more powerful with higher FR accuracy and robust against age factor. Consequently, AAD approach is able to take the advantages of both FR datasets with and without age labels to train an AiFR model. Far apart from prior distillation methods mainly focusing on accuracy and compression ratios in closed-set problems, our AAD aims to solve the open-set problem, i.e. large-scale face recognition. Evaluations on LFW, IJB-B and IJB-C Janus, AgeDB and MegaFace-FGNet with one million distractors have demonstrated the efficiency of the proposed approach. This work also presents a new longitudinal face aging (LogiFace) database for further studies in age-related facial problems in future.Comment: arXiv admin note: substantial text overlap with arXiv:1905.1062

Stimulation of a Suprachoroidal Retinal Prosthesis Drives Cortical Responses in a Feline Model of Retinal Degeneration

PURPOSE. Retinal prostheses have emerged as a promising technology to restore vision in patients with severe photoreceptor degeneration. To better understand how neural degeneration affects the efficacy of electronic implants, we investigated the function of a suprachoroidal retinal implant in a feline model. METHODS. Unilateral retinal degeneration was induced in four adult felines by intravitreal injection of adenosine triphosphate (ATP). Twelve weeks post injection, animals received suprachoroidal electrode array implants in each eye, and responses to electrical stimulation were obtained using multiunit recordings from the visual cortex. Histologic measurements of neural and glial changes in the retina at the implant site were correlated with cortical thresholds from individual stimulating electrodes. RESULTS. Adenosine triphosphate-injected eyes displayed changes consistent with mid-to-late stage retinal degeneration and remodeling. A significant increase in electrical charge was required to induce a cortical response from stimulation of the degenerated retina compared to that in the fellow control eye. Spatial and temporal characteristics of the electrically evoked cortical responses were no different between eyes. Individual electrode thresholds varied in both the control and the ATP-injected eyes and were correlated with ganglion cell density. In ATP-injected eyes, cortical threshold was also independently correlated with an increase in the extent of retinal gliosis. CONCLUSIONS. These data suggest that even when ganglion cell density remains unaffected, glial changes in the retina following degeneration can influence the efficacy of suprachoroidal electrical stimulation. A better understanding of how glial change impacts retinal prosthesis function may help to further the optimization of retinal implants