A Pigmented Iris Lesion.

A patient in their mid-60s presented with a left iris pigmented lesion that had been present for decades and remained stable in size. What would you do next?

Acute macular neuroretinopathy following Pfizer-BioNTech COVID-19 vaccination.

PURPOSE: To describe a case of acute macular neuroretinopathy (AMN) in a patient immediately following administration of the Pfizer-BioNTech COVID-19 vaccine. OBSERVATIONS: The patient complained of paracentral scotoma supported by paracentral visual field loss on multiple Humphrey visual fields that corresponded to outer retinal pathology on optical coherence tomography. The patient's symptoms resolved without treatment. CONCLUSIONS AND IMPORTANCE: We conclude that the clinical testing demonstrated findings consistent with AMN. AMN may be an exceedingly rare adverse ocular effect of a novel vaccine and likely only in the setting of multiple other risk factors. Despite this, we strongly recommend vaccination against COVID-19.

An Unusual Granular Ulcer Secondary Oral Tuberculosis of Vestibule Mandibular Mucosa.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. In the oral cavity, clinical manifestations are considered atypical lesions. The aim of this study was to report an unusual granular ulcer secondary oral TB that does not heal, chronic, had irregular appearance with deep depression of 2 cm in diameter, and was located in buccal mucosa of the premolar area-the left mandibular arch, of a 42-year-old woman. The patient was subjected to surgical excision of ulcer in its entirety and accordingly a periodontal plastic surgery in the area of the lesion was performed positioning an autograft subepithelial connective tissue. We obtained optimal results in improving oral health, function, and patient's comfort, in postoperative controls at 15, 30, and 60 days, respectively.

Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development.

What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGCs. These data place Sox4 downstream of RE1 silencing transcription factor in regulating RGC fate, and further describe a newly identified, Sox4-regulated site for post-translational modification with small ubiquitin-related modifier (SUMOylation) in Sox11, which suppresses Sox11's nuclear localization and its ability to promote RGC differentiation, providing a mechanism for the SoxC familial compensation observed here and elsewhere in the nervous system. These data define novel regulatory mechanisms for this SoxC molecular network, and suggest pro-RGC molecular approaches for cell replacement-based therapies for glaucoma and other optic neuropathies.SIGNIFICANCE STATEMENT Glaucoma is the most common cause of blindness worldwide and, along with other optic neuropathies, is characterized by loss of retinal ganglion cells (RGCs). Unfortunately, vision and RGC loss are irreversible, and lead to bilateral blindness in ∼14% of all diagnosed patients. Differentiated and transplanted RGC-like cells derived from stem cells have the potential to replace neurons that have already been lost and thereby to restore visual function. These data uncover new mechanisms of retinal progenitor cell (RPC)-to-RGC and human stem cell-to-RGC fate specification, and take a significant step toward understanding neuronal and retinal development and ultimately cell-transplant therapy.

Survival and integration of developing and progenitor-derived retinal ganglion cells following transplantation.

There is considerable interest in transplanting stem cells or progenitors into the injured nervous system and enhancing their differentiation into mature, integrated, functional neurons. Little is known, however, about what intrinsic or extrinsic signals control the integration of differentiated neurons, either during development or in the adult. Here we ask whether purified, postmitotic, differentiated retinal ganglion cells (RGCs) directly isolated from rat retina or derived from in vitro-differentiated retinal progenitor cells can survive, migrate, extend neurites, and form morphologic synapses in a host retina, in vivo and ex vivo. We found that acutely purified primary and in vitro-differentiated RGCs survive transplantation and migrate into deeper retinal layers, including into their normal environment, the ganglion cell layer (GCL). Transplanted RGCs from a wide range of developmental ages, but not from adults, were capable of extending lengthy neurites in the normal and injured adult rat retina ex vivo and to a lesser degree after transplantation in vivo. We have also demonstrated that RGCs may be differentiated and purified from retinal precursor cultures and that they share many of the same cell biological properties as primary RGCs. We have established that progenitor-derived RGCs have similar capacity for integration as developing primary RGCs but appear to form a lower number of presynaptic punctae. This work provides insight for further understanding of the integration of developing RGCs into their normal environment and following injury.

A tunable synthetic hydrogel system for culture of retinal ganglion cells and amacrine cells.

The central nervous system consists of complex groups of individual cells that receive electrical, chemical and physical signals from their local environment. Standard in vitro cell culture methods rely on two-dimensional (2-D) substrates that poorly simulate in vivo neural architecture. Neural cells grown in three-dimensional (3-D) culture systems may provide an opportunity to study more accurate representations of the in vivo environment than 2-D cultures. Furthermore, each specific type of neuron depends on discrete compositions and physical properties of their local environment. Previously, we developed a library of hydrogels composed of poly(ethylene glycol) and poly(l-lysine) which exhibit a wide range of mechanical properties. Here, we identified specific scaffolds from this library that readily support the survival, migration and neurite outgrowth of purified retinal ganglion cells and amacrine cells. These data address important biological questions about the interaction of neurons with the physical and chemical properties of their local environment and provide further insight for engineering neural tissue for cell-replacement therapies following injury.

Tissue engineering the retinal ganglion cell nerve fiber layer.

Retinal degenerative diseases, such as glaucoma and macular degeneration, affect millions of people worldwide and ultimately lead to retinal cell death and blindness. Cell transplantation therapies for photoreceptors demonstrate integration and restoration of function, but transplantation into the ganglion cell layer is more complex, requiring guidance of axons from transplanted cells to the optic nerve head in order to reach targets in the brain. Here we create a biodegradable electrospun (ES) scaffold designed to direct the growth of retinal ganglion cell (RGC) axons radially, mimicking axon orientation in the retina. Using this scaffold we observed an increase in RGC survival and no significant change in their electrophysiological properties. When analyzed for alignment, 81% of RGCs were observed to project axons radially along the scaffold fibers, with no difference in alignment compared to the nerve fiber layer of retinal explants. When transplanted onto retinal explants, RGCs on ES scaffolds followed the radial pattern of the host retinal nerve fibers, whereas RGCs transplanted directly grew axons in a random pattern. Thus, the use of this scaffold as a cell delivery device represents a significant step towards the use of cell transplant therapies for the treatment of glaucoma and other retinal degenerative diseases.