ABSTRACT
Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal MÏller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozygous or homozygous loss-of-function mutants of Ptbp1 in adult retinal MÏller glia does not lead to any detectable level of neuronal conversion. Only a few changes in gene expression are observed in MÏller glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage-tracing methods in studying cell-type conversion.
Subject(s)
Heterogeneous-Nuclear Ribonucleoproteins , Polypyrimidine Tract-Binding Protein , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Neuroglia/metabolism , Neurons/metabolism , Polypyrimidine Tract-Binding Protein/genetics , Polypyrimidine Tract-Binding Protein/metabolism , Retina/metabolismABSTRACT
PURPOSE: The objective of this case series was to describe the clinical and imaging features of focal choroidal elevations (FCE), which are chorioretinal contour changes induced by individual choroidal vessels within an overall thin-appearing choroid. METHODS: A total of 787 enhanced depth imaging (EDI) spectral domain optical coherence tomography (SD-OCT) patient images were initially screened for the presence of FCE. Prospective imaging analysis of 38 patients with FCE was done. Mean central macular choroidal thickness (CMCT), FCE location, FCE vessel lumen diameter, patient demographics, cycloplegic autorefraction, ophthalmoscopic findings, and presence of choroidal neovascularization (CNV) in the fellow eye were recorded. RESULTS: FCE were observed in 25 patients with age-related macular degeneration (ARMD), in 5 patients with high myopia, and in 8 patients with age-related choroidal atrophy (ARCA). Mean patient age was 80 ± 9.4 years. Mean CMCT was 86 ± 40 µm. Mean lumen diameter of the vessels inducing FCE was 131 ± 33 µm. CONCLUSIONS: FCE are relatively frequently encountered morphologic features of elderly patients with ARMD, high myopia, and ARCA, and have a distinct clinical and imaging morphology which differs from classically described chorioretinal folds. The lesions may commonly be mistaken for pigment epithelial detachments on ophthalmoscopy, may be associated with CNV in fellow eyes, and have a characteristic SD-OCT appearance.
ABSTRACT
Improvements in retinal imaging have recently elucidated structural patterns in the development of macular edema, particularly involving the inner nuclear layer. Here, the authors describe two cases of isolated inner nuclear layer cystic changes in the phakic fellow eye of patients with pseudophakic cystoid macular edema. Both cases improved with treatment of their fellow eye and resolution of contralateral macular edema. The authors hypothesize potential pathomechanisms for this likely common but under-recognized phenomenon. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:522-524.].
Subject(s)
Macular Edema/pathology , Pseudophakia/pathology , Acute Disease , Aged , Anti-Inflammatory Agents/therapeutic use , Female , Humans , Male , Middle Aged , Treatment Outcome , Triamcinolone Acetonide/therapeutic useABSTRACT
The objective of this study is to describe the clinical utility and morphologic characteristics of peripheral vitreoretinal interface abnormalities with spectral domain optical coherence tomography (SD-OCT). A prospective imaging analysis of 43 patients with peripheral vitreoretinal interface abnormalities seen on binocular indirect examination with scleral indentation was done. SD-OCT was evaluated for image quality and structural findings. Laser retinopexy was performed to surround all retinal breaks containing a full-thickness component via SD-OCT. Acceptable image quality for inclusion was obtained in 39/43 (91%) patients. Mean age was 41 ± 22 years, and mean follow-up was 14 ± 1.6 months. Decision to treat was altered following SD-OCT in 5% of the patients. Two cases of previously diagnosed operculated holes were found on SD-OCT to be partial-thickness operculated breaks or focal operculated schisis. Peripheral SD-OCT is a reliable and useful technique to examine the structural features of vitreoretinal interface abnormalities in vivo. This imaging modality is useful in the clinical management of suspected retinal breaks identified with indirect ophthalmoscopy.
