Neural organoids provide a powerful tool for investigating neural development, modeling neural diseases, screening drugs, and developing cell-based therapies. Somatic cells have previously been reprogrammed by transcription factors (TFs) into sensory ganglion (SG) neurons but not SG organoids. We identify a combination of triple TFs Ascl1, Brn3b/3a, and Isl1 (ABI) as an efficient means to reprogram mouse and human fibroblasts into self-organized and networked induced SG (iSG) organoids. The iSG neurons exhibit molecular features, subtype diversity, electrophysiological and calcium response properties, and innervation patterns characteristic of peripheral sensory neurons. Moreover, we have defined retinal ganglion cell (RGC)–specific identifiers to demonstrate the ability for ABI to reprogram induced RGCs (iRGCs) from fibroblasts. Unlike iSG neurons, iRGCs maintain a scattering distribution pattern characteristic of endogenous RGCs. iSG organoids may serve as a model to decipher the pathogenesis of sensorineural diseases and screen effective drugs and a source for cell replacement therapy.
The aim of this study was to identify the morphological features of the retina and choroid in Macaca fascicularis of different ages using multimodal imaging. Methods A total of 27 Macaca fascicularis with no ocular diseases were studied (mean age, 104.2 months; range, 1.2-223.6 months). Multimodal imaging was obtained from each subject. The morphological features were compared within four subgroups according to age. Results On spectrum-domain optical coherence tomography (SD-OCT), four hyper-reflective bands could be observed in the outer retina in non-infant macaques (21/21, 100%), while the interdigitation zone could not be observed in the six infant macaques. A narrow hypo-reflective band just posterior to the retinal pigment epithelium (RPE) was noted in most eyes (25/ 27, 92.6%). The choroidal-scleral junction (CSJ) was visible in 83.3% of infants but only in 12.5% of adults and 14.3% of the geriatric population, and it could not be seen in juveniles. There was a significant difference in CSJ visibility between the infant group and the other three groups (P < 0.001). Tessellated fundus, in which the choroidal vessels are visible through the retina, could be observed clearly with near-infrared reflectance imaging (NIR). Some granular spots were noted in juveniles, and they accumulated dramatically with age, but were absent in infants. Conclusion Notable morphological features can be observed in the Macaca fascicularis subjects using multimodal imaging, and these features vary distinctly according to their age. It is important to note that infant macaques had no interdigitation zone, while the other macaques had no visible CSJ but did have well-defined choroidal capillaries. Age and the features should be considered seriously in future animal studies.
Macular structure and function can progressively improve in the first year after successful RRD repair, including in the external limiting membrane, damage to which has previously been thought to be irreversible. SD-OCT serves as a useful tool to monitor postoperative retinal recovery.
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